Naïve adaptive immune receptor repertoires in celiac disease assessed by machine learning; impact of the HLA-DQ2.5 allotype on the TCR repertoire - Aengus Officer; Ida Lindeman; Milena Pavlovic; Christin Lund-Andersen; Eivind Ness-Jensen; Geir Kjetil Sandve; Ludvig M. Sollid (Immunogenetics, 2026)
The adaptive immune receptor repertoire (AIRR) - the collection of an individual’s B-cell and T-cell receptors (BCRs and TCRs, respectively) - encodes cumulative immune history and is shaped by both germline genetics and environmental exposures. Skewed repertoires have been linked to infections, vaccination responses and autoimmune diseases such as celiac disease (CeD) where biased usage of immunoglobulin and T-cell receptor genes reactive to disease relevant antigens has been reported. Motivated by evidence that germline variation, notably human leukocyte antigen (HLA), influences naïve AIRRs and by prior machine-learning studies that classified CeD using naïve BCR AIRR-sequencing (AIRR-seq) data, we applied machine learning analysis to naïve CD4 + TCR and naïve BCR AIRR-seq repertoires to test whether repertoire features can distinguish subjects with CeD from controls and to identify drivers of such classification. Naïve CD4 + TCR repertoires yielded moderate diagnosis classification, but this signal was largely explained by enrichment of the HLA-DQ2.5 allotype. TCR variable gene frequencies predicted HLA-DQ2.5 status with high accuracy and controlling for HLA-DQ2.5 abolished TCR-based diagnosis classification. In contrast, naïve BCR repertoires could not be used to classify CeD. Overall, our findings show that germline HLA variation significantly affects naïve TCR composition and thereby indirectly facilitates moderately successful CeD status classification.

Genetic association of immunosenescence to immune decline - Mohammad Y. Alshahrani; Zahraa AlKhafaje; Uday Abdul-Reda Hussein; Zahraa Adel; Ola Kamal A. Alkadir; Ahmed Aldulaimi; Rafid Kamal Jameel; Rafid Jihad Albadr; Mariem Alwan; Aseel Smerat (Immunogenetics, 2026)

Causal relationship and pathogenic mechanism analysis of breast cancer and coronary heart disease based on mendelian randomization and transcriptome data analysis - Mingbin Xie; Yuanhong Wu; Xinyao Jin; Fengchun Jiang; Qiang Yao (Immunogenetics, 2026)

Genotype–phenotype correlations in autoimmune and autoinflammatory diseases: An NGS-based immunogenetic cohort study - Esra Çolak Geniş; Fethi Sırrı Çam (Immunogenetics, 2026)

Elevated interleukin-36γ and gene polymorphisms implicate novel risk in essential hypertension - Alishba Kainat; Fazlul Aziz Mian; Muhammad Asif Nawaz Khan; Mubeen Tabish Nasim; Syed Muhammad Nurulain; Nazia Bibi; Syed Tahir Abbas Shah; Muhammad Jadoon Khan; Sabir Hussain (Immunogenetics, 2026)

Unraveling the genomic structures, conserved functional domains and evolutionary dynamics of beta-defensins in Bubalus bubalis and Ovis aries - Sonam Yadav; Chanchal Rana; Fanny Josan; Mir Ahmad Habib; Aditya Patel; Vikrant Gaur; Rakesh Kumar (Immunogenetics, 2026)

Genetic characterization of the TAPBP and its allelic association with BF2 in the chicken major histocompatibility complex - Roshani Fernando; Trisha Nicole Agulto; Eunjin Cho; Jaewon Kim; Andy van Hateren; Minjun Kim; Prabuddha Manjula; Jun Heon Lee (Immunogenetics, 2026)

Reconstructed amphibian heavy-chain constant regions support a mosaic origin of IgXA with IgY-like CH1–CH2, an intermediate CH3, and an IgM-like CH4 - Francisco Gambón-Deza (Immunogenetics, 2026)

Climate factors and selection shape MHC class II diversity in a montane wild sheep (Ovis ammon) - Zi-Yue Tian; Jin-Yi Li; Zhen-Yuan Cai; Shamshidin Abduriyim (Immunogenetics, 2026)

Deciphering APOBEC1 in Avians: unravelling loss events and functional insights - Aswin S. Soman; Nagarjun Vijay (Immunogenetics, 2026)

Allelic diversity and selection at the MHC class I and class II in a long-distance migratory shorebird, the Hudsonian Godwit (Limosa haemastica) - Kiara Fernández; Nathan R. Senner; James A. Johnson; Juan G. Navedo; Claudio Verdugo (Immunogenetics, 2026)

Genetic and immunological determinants of Pemphigus vulgaris: integrative analysis of HLA-DRB1 and FCGR2B variants - Burak Kaan Kasap; Bayram Toraman; Burçin Kurt; Hande Ermis; Deniz Aksu Arıca (Immunogenetics, 2026)
Pemphigus vulgaris (PV) is a rare autoimmune blistering disease mediated by pathogenic autoantibodies. Although both HLA and non-HLA loci contribute to disease susceptibility, their combined roles in immune regulation remain incompletely understood. This study investigated the joint contribution of HLA-DRB1 and FCGR2B variants to PV susceptibility within an integrative immunogenetic framework. Genotype data from 286 individuals (200 controls and 86 PV patients) were analyzed using bias-reduced association models, two-locus genotype combination analyses, and cumulative genetic risk modeling. Gene–gene relationships were explored through epistasis testing, while functional relevance was examined using biological annotation approaches. HLA-DRB1*04:02 and *14:01 were significantly associated with increased PV risk, whereas *11:01 and *16:01 demonstrated protective effects after multiple testing correction (q < 0.05). The FCGR2B c.671T > C (I232T) variant showed a modest effect in single-locus analyses but did not remain statistically significant after correction for multiple testing. Several two-locus genotype combinations involving FCGR2B and HLA-DRB1 were enriched among patients; however, interaction analyses supported an additive immunogenetic architecture rather than epistasis. Genetic risk modeling demonstrated improved discrimination with weighted scores, and explainable machine-learning analysis identified HLA-DRB1 as the dominant predictor, with FCGR2B contributing a secondary modulatory signal. These findings delineate an additive immunogenetic framework underlying PV susceptibility, emphasizing the central role of HLA-DRB1. Although FCGR2B did not retain independent statistical significance after multiple-testing correction, the results suggest a potential modulatory contribution within the broader immunogenetic architecture of PV.

Identification of gene conversion events in horse IGHV suggests preferential hotspots for diversification - Juliana Edelvacy Lima Pinto; João Henrique Brandão Gervásio; Joseph Chi-fung Ng; Adriano Gomes-Silva; Herbert L. de Matos Guedes; Luiz Cunha; Leda R. Castilho; Jerson Lima da Silva; Glória Regina Franco; Carlena Navas; Liza Figueiredo Felicori (Immunogenetics, 2026)
The humoral immune response relies on a diverse antibody repertoire, which is expanded through processes such as somatic hypermutation, class-switch recombination and gene conversion. These processes are primarily mediated by activation-induced cytidine deaminase (AID). Gene conversion generates diversity in immunoglobulin heavy and light chains (IGHVs) in species such as chickens and rabbits, though it has not been widely studied. Since 80% of the equine IGHV repertoire originates from only three functional gene segments, we examined gene conversion events in horses to assess their role in antibody diversification. Using a modified version of BrepConvert, which optimized analysis time, we identified gene conversion events in 6.9% of immunoglobulin sequences. The results showed a local preference, with most events occurring at the beginning of framework region 1 (FR1) and within complementarity-determining region 2 (CDR2). Pseudogenes IGHV4-35, IGHV4-53, and IGHV4-38 were utilized most frequently, while functional genes IGHV4-21, IGHV4-22, and IGHV4-29 exhibited the highest event frequencies. Interestingly, while most mismatched regions were only three nucleotides long, 91% of these events are flanked by specific sequences (six nucleotides at the 5′ end and one nucleotide at the 3′ end). Furthermore, functional pseudogene pairs often share identical leader regions of 5–26 nucleotides, suggesting expanded events. We also identified a potential association between these events and local non-B DNA conformations, as well as with the zinc finger protein ZNF691, which supports the involvement of DNA-binding factors. Together, these findings demonstrate that gene conversion significantly contributes to equine antibody diversity by targeting specific IGHV regions.

Genetic and evolutionary characteristics of the major histocompatibility complex class II β-chain genes of a large colony of captive king penguins (Aptenodytes patagonicus) - Reona Dei; Yukie Miyazawa; Natsumi Ota; Hiroki Narashima; Eri Kikkawa; Shingo Suzuki; Atsuko Shigenari; Sayaka Ito; Tomi T. Tsuda; Jerzy K. Kulski; Takashi Shiina; Yuki F. Kita (Immunogenetics, 2026)

The digital keystone: how artificial intelligence is reshaping HLA research and clinical practice - Gamze Sonmez; Yigit Yazarkan; Deniz Cagdas (Immunogenetics, 2026)
The human leukocyte antigen (HLA) system underpins allorecognition and shapes the response to infection, autoimmunity, and treatment response. Technological advances from serology to next-generation sequencing now enable full-gene characterization and four-field HLA nomenclature, while artificial intelligence (AI) and machine learning are transforming the data generation, interpretation, and clinical use. This review summarizes the progress on the technical developments in the HLA era, which could be evaluated in three perspectives. First, we survey AI for antigen processing and T-cell recognition, including HLA–peptide binding, presentation, and T cell receptor (TCR)–epitope models, and outline their effects on applications like neoantigen discovery, vaccine design, and tolerance induction. Since there are still persistent gaps in immunogenicity prediction and coverage of rare alleles, secondly, we evaluated HLA imputation from the single nucleotide polymorphism (SNP) arrays and low-coverage whole-genome sequencing, highlighting deep learning models that improve accuracy for common and low-frequency alleles, and the critical role of diverse reference panels. Third, we assessed the AI-enabled transplant decision support: survival and graft-versus-host disease forecasting from registry data, donor ranking beyond simple allele match, and crossmatch compatibility prediction. We integrate emerging biology, non-classical HLA molecules, allele-specific expression, and HLA loss of heterozygosity, as key modulators of immune activation and evasion with implications for donor selection, infectious diseases, vaccinology, inflammatory disease, and cancer therapy. To accelerate safe clinical translation, we need to have standards for data governance, fairness auditing, validation and calibration, explainability, robustness, monitoring, and human oversight. By bridging core HLA principles with recent biological insights and AI innovations, we outline a path toward reproducible and equitable clinical translation to immunogenomics in transplantation, infectious, inflammatory, oncologic diseases, and precision vaccinology.

Evolution of CCR1 and CCR1L1 reveals complex duplication scenarios in Muroids and Ruminants - João Pedro Marques; Ana Pinheiro; Pedro José Esteves (Immunogenetics, 2026)

Deciphering the genetic control of immune cell function at single-cell resolution: Disease-Specific Cis-eQTLs analysis of COVID-19 - E. I. Romanova; D. I. Tychinin; A. M. Shaymardanov; V. E. Akimov; A. V. Korobeinikova; V. V. Shiryagin; N. I. Guskova; V. A. Astafieva; A. S. Shingaliev; O. A. Antonova; L. A. Golubnikova; S. I. Mitrofanov; et al. (Immunogenetics, 2026)

Class switched bovine ultralong CDR H3 amplicons versus canonical in immune and non-immune tissues - Karina L. Hissen; Morgan Sheppard; Jeannine A. Ott; Kerstin K. Landrock; Casey Whitley; Nicholas Ebert; J. M. Cody Horton; Nicole A. Glenn; Yoonsung Jung; Vaughn V. Smider; Michael F. Criscitiello (Immunogenetics, 2026)
Within the bovine immune response, a distinct type of immunoglobulin (Ig), known as ultralong complementarity-determining region 3 (CDR3) antibodies, coexists alongside canonical Igs. These ultralong heavy chains (HC) feature a remarkable structure with a lengthened CDR3 of the heavy chain (CDR H3), allowing them to adopt either a smaller and more extended paratope than canonical antibodies. However, very little is known about the distribution of ultralong CDR H3s in cattle tissues and which isotypes they are ultimately associated with. This study analyzed and quantified the amplicons of the five immunoglobulin isotypes (IgM, IgD, IgG, IgA, and IgE) for both the canonical and ultralong CDR H3 throughout 24 Bos taurus tissues. IgH amplicons analysis identified an extensive repertoire of expressed canonical and ultralong CDR H3s of each isotype in most tissues. Ultralong cattle Igs were preferentially switched to the IgG isotype, especially in the medial retropharyngeal lymph node draining the immunization site. Additionally, B cells producing canonical Igs in bone marrow switched most to the IgG isotype. These data suggest that ultralong CDR H3 may be uniquely qualified to handle some antigens. A more comprehensive understanding of isotype and tissue-specific immune responses of these unusual antibodies can provide a deeper insight into their function within the overall cattle immune system, offering unique opportunities for innovations for in both bovine health and human immunotherapeutics.

NKG2D genetic variants and cancer susceptibility: Integrating case-control evidence with meta-analysis - Nguyen Hoang Viet; Le Thanh Dong; Do Tung Dac; Hai Ha Long Le; Le Thi Phuong; Pham Phuong Thao; Hoang Thao Giang Nguyen; J. Luis Espinoza (Immunogenetics, 2026)

Can the simple chicken MHC provide insight into the balance of autoimmunity and infectious disease? - Enock M. Mararo; Anastasia Goryanin; Jim Kaufman (Immunogenetics, 2025)

Necessity of individual VDJ-databases for annotating antibody heavy chain characteristics in non-human primates - Aafke Aartse; Jacco G. J. Bakx; Daniella Mortier; Sam Hofman; Petra Mooij; Mathieu Claireaux; Dirk Eggink; Willy M. Bogers; Edmond J. Remarque; Martin M. Corcoran; Gunilla B. Karlsson Hedestam; Ronald E. Bontrop; et al. (Immunogenetics, 2025)

Evolution of SAMD9 and SAMD9L genes in primates: a complex history of gene loss, gene duplication and pseudogenization - António Duarte; Ana Pinheiro; Pedro José Esteves (Immunogenetics, 2025)

Compact genomic architecture of the axolotl MHC region: setting the record straight - Magdalena Migalska; Krzysztof Fluder; Katarzyna Dudek; Wiesław Babik (Immunogenetics, 2025)
The Major Histocompatibility Complex (MHC) is a gene-dense genomic region essential to adaptive immunity, exhibiting both conserved features and lineage-specific rearrangements across jawed vertebrates. Amphibians, as basal tetrapods, offer critical insights into MHC evolution; however, research has largely focused on anurans (e.g., Xenopus ), while urodeles remain understudied, primarily due to their exceptionally large genomes. With recent advances in sequencing technologies, chromosome-scale assemblies for urodeles are now becoming available, opening new opportunities to explore their MHC architecture. Yet, the MHC region remains notoriously challenging to annotate due to its complexity, high polymorphism, and dynamic evolutionary history. For instance, the initial annotation of the axolotl ( Ambystoma mexicanum ) MHC relied heavily on synteny with mammalian genomes, which led to an overestimation of its size and misinterpretation of its structure. These inaccuracies have fueled evolutionary debates regarding the ancestral genomic structure of the MHC. Here, we present a comprehensive re-annotation of the axolotl MHC, revealing a typical organization found in tetrapods other than eutherian mammals: core MHC region with several, expressed MHC class I genes, tightly linked to their antigen processing genes, and to single loci of MHC class II genes. Contrary to the previous report, class I and class II genes are not separated by class III genes, and the overall MHC region is relatively compact (by axolotl genome standards). These findings correct earlier misconceptions and emphasize the need for annotation strategies that reflect the complex and lineage-specific nature of genomic regions rich in immune genes.

Evaluation of lymphoid defects in specific inborn errors of immunity using a single-tube multicolor flow cytometry assay - Reja Tanveer; Sanchi Chawla; Saniya Sharma; Ankur Jindal; Manpreet Dhaliwal; Gurjit Kaur; Pallavi L. Nadig; Kanika Arora; Taru Goyal; Arjun Ram; Satish Sharma; Pandiarajan Vignesh; et al. (Immunogenetics, 2025)

Genetic insights into the major histocompatibility complex class I BF2 gene of Korean native chickens in relation to the LEI0258 microsatellite marker and the 90-SNP panel - Trisha Nicole Agulto; Minjun Kim; Prabuddha Manjula; Roshani Fernando; Jim Kaufman; Jun Heon Lee (Immunogenetics, 2025)

Immunoglobulin genetics of a model squamate reptile, Tiliqua rugosa - Jordan M. Sampson; Kieran J. Mikolajova; Michael G. Gardner; Terry Bertozzi; Robert D. Miller (Immunogenetics, 2025)

Association between single-nucleotide polymorphism rs868875 of CLEC4M gene and clinical severity of COVID-19 in a Brazilian population - Steffany Larissa Galdino Galisa; Marcus Villander Barros de Oliveira Sá; Natália Machado Tavares; Viviane Sampaio Boaventura; Juliana Ribeiro Caldas; Raquel Bispo de São Pedro; Carlos Dornels Freire de Souza; Anderson da Costa Armstrong; Pablo Rafael Silveira Oliveira; Rodrigo Feliciano do Carmo; Luydson Richardson Silva Vasconcelos (Immunogenetics, 2025)

Genetic diversity of BoLA-DRB3 in Latin American Creole cattle: an update of the state of the art - Olivia Marcuzzi; Guillermo Giovambattista; Ariel Loza Vega; Juan Antonio Pereira Rico; Maria Florencia Ortega Masague; Liz Aurora Castro Rojas; Ruben Martinez; Odalys Uffo Reinosa; Aronggaowa Bao; Sonoko Watanuki; Noriko Fukushi; Fumihiro Nagata; et al. (Immunogenetics, 2025)
Genetic diversity of the bovine leukocyte antigen BoLA-DRB3 gene has been reported in cattle breeds due to its central role in immune response. However, the gene has been characterized in only a few Latin American native cattle breeds. In this study, we aimed to investigate the genetic diversity of this gene in other native bovine breeds from Argentina, Bolivia, Cuba, and Paraguay, thereby contributing to the global knowledge regarding BoLA-DRB3 diversity. The gene was genotyped using PCR-sequence-based typing; 60 reported alleles and one novel variant were identified. The observed and expected heterozygosity values were higher than 0.81, and only two populations showed deviation from the Hardy–Weinberg equilibrium. The Slatkin neutrality test indicated even allele distribution in one population. Nucleotide diversity and the number of pairwise differences ranged from 0.073 to 0.081 and 17.88 to 20.19, respectively. The mean number of non-synonymous and synonymous nucleotide substitutions was estimated for the entire sequence and the antigen-binding site (ABS), with higher values observed in the latter. Amino acid motifs varied in their frequencies, and the diversifying selection index (ω) at each amino acid was high in more than 25 sites, with the most prominent peaks located in the ABS. A distribution of native cattle according to their historical and geographical origin and degree of Zebu gene introgression demonstrated that the Latin American native populations exhibit high variability in the BoLA-DRB3 gene, including private alleles, and a distinct genetic profile, making them a valuable genetic resource and emphasizing the importance of their conservation.

Immunoglobulin GM (γ marker) and FcγR genotypes interact to contribute to the magnitude of ADCC against SARS CoV-2 S-transfected cells - Janardan P. Pandey; Aryan M. Namboodiri; Paul J. Nietert (Immunogenetics, 2025)
Immunoglobulin GM (γ marker) and KM (κ marker) allotypes have been shown to be associated with antibody responses to several viruses, but their role in immunity to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)—the causative agent of Coronavirus disease 2019 (COVID-19)—has not been investigated. The aim of the present investigation was to determine the contribution of GM, KM, and FcγR genotypes to the magnitude of humoral immunity to SARS-CoV-2 and to the antibody-dependent cell-mediated cytotoxicity (ADCC) of SARS CoV-2 S-transfected cells. ADCC is a major host immunosurveillance mechanism against viruses and the leading mechanism underlying the clinical efficacy of therapeutic monoclonal antibodies. We genotyped 124 unvaccinated people for several GM, KM, and FcγR alleles, measured IgG antibodies to the receptor-binding domain of the spike protein (S-RBD) of SARS CoV-2, and quantitated the level of ADCC against SARS CoV-2 S-transfected cells. None of the associations between genotypes and antibody levels were statistically significant, potentially a reflection of relatively small sample sizes. However, we found a significant interactive effect of GM and FcγRIIIa valine (V)/phenylalanine (F) genotypes on the ADCC of SARS CoV-2 S-transfected cells. In the FcγRIIIa F/F group, the mean ADCC value was significantly (p = 0.03) lower among those with GM 17/17 (mean = 45.2) when compared to those with GM 3/3 (mean = 60.2). In the FcγRIIIa V/V group, the mean ADCC value was not significantly (p = 0.68) lower among those with GM 17/17 (mean = 52.5) when compared to those with GM 3/3 (mean = 55.4). These results may help devise potent immunotherapy against emerging SARS CoV-2 variants.

Dysregulation of lncRNAs in NK cells from breast cancer patients: implications for NK cell functions - Mona Rady; Eman Mohamed; Ola Khorshid; Khaled Abou-Aisha (Immunogenetics, 2025)
Natural killer (NK) cells, a key component of the innate immune system, play a crucial role in detecting and eliminating cancer cells, contributing to cancer immune surveillance. Increasing evidence suggests that NK cell functions are regulated by epigenetic mechanisms, including the influence of long non-coding RNAs (lncRNAs). These lncRNAs, transcripts longer than 200 nucleotides, are emerging as important regulators of gene expression. In this study, we investigated the expression of 84 lncRNAs in NK cells isolated from the peripheral blood of patients with invasive breast cancer. Using lncRNA PCR array profiling, we identified 26 differentially expressed lncRNAs in circulating NK cells isolated from peripheral blood of breast cancer patients, with 10 genes showing significant downregulation and 16 genes showing significant upregulation. Gene ontology (GO) and functional enrichment analysis revealed that among the ten downregulated lncRNAs, four lncRNAs have deposited gene ontology terms and known biological functions. These lncRNAs are PTENP1-AS (fold change 0.27, P = 0.0206), TSIX (fold change 0.05, P = 0.0037), XIST (fold change 0.42, P = 0.007), and CCAT1 (fold change 0.09, P = 0.0191). On the other hand, among the 16 upregulated lncRNAs, five lncRNAs have deposited gene ontology terms and known biological functions. These lncRNAs are GNAS-AS1 (fold change 5.10, P = 0.0104), MEG3 (fold change 46.85, P = 0.0138), CDKN2B-AS1 (fold change 81.80, P = 0.0087), HOTAIR (fold change 6.86, P = 0.0042), and AIRN (fold change 7.97, P = 0.0379). Functional enrichment analysis indicated that the downregulated lncRNAs were mainly involved in biological processes such as chromatin organization, epigenetic regulation of gene expression, and dosage compensation via X chromosome inactivation, while the upregulated lncRNAs were linked to epigenetic regulation, genomic imprinting, and chromatin remodeling. These enrichments were identified using Bonferroni correction with an adjusted P -value < 0.05. Given the biological functions of the dysregulated lncRNAs in NK cells from breast cancer patients, this has the potential to significantly impact the antitumor functionality of NK cells, possibly contributing to the impaired immune surveillance and tumor control commonly observed in breast cancer patients. Understanding the dysregulation of lncRNAs in NK cells may provide critical insights into the mechanisms underlying impaired NK cell function in breast cancer, offering promising approaches for developing immunotherapies aiming at restoring NK cell activity in cancer patients.

Molecular evolution of the transcription factor PRDM genes and expression profiles in response to stimulations and spinal cord injury repair in lamprey (Lethenteron reissneri) - Jinyang Guo; Xinyu Du; Jiaqi Wu; Boting Lan; Ning Yang; Peng Su (Immunogenetics, 2025)

Full-length gene polymorphism of the non-classical HLA-E in Estonian individuals - Timo I. Olieslagers; Ingrid Tagen; Mathijs Groeneweg; Marcel G. J. Tilanus; Lotte Wieten; Christina E. M. Voorter (Immunogenetics, 2025)
Estonia is a small country in the Baltic region of Northern Europe with 1.3 million inhabitants. As a coastal area, the population of Estonia was subjected to migration influences. Due to this admixture of populations, HLA gene diversity in Estonia is interesting to study with regard to allele frequencies, haplotypes, and polymorphism. In this study, we focused on HLA-E polymorphism within the Estonian population and compared these with the polymorphism identified in other populations. Full-length HLA-E sequencing of 143 individuals originating from Estonia show dimorphism frequencies at amino acid position 107 (0.55 R vs 0.45 G) comparable to other populations. Within the study population, 16 different HLA-E alleles were identified, including four novel alleles. These 16 alleles encode four different protein variants. Despite a strong differentiation between the South-East and the rest of the Estonian country, no allele frequency differences for HLA-E between these regions were identified. Comparing the allele and SNP frequencies to frequencies found in the different neighboring countries revealed no major differences, except for the SNP encoding for HLA-E*01:06 . Association analysis between classical HLA class I genes and polymorphism at amino acid position 107 of HLA-E revealed higher frequencies of HLA-A*01 with R107 and HLA-A*03 and HLA-C*04 with G107. In summary, our study provides new insights into HLA-E variation within the Estonian population and demonstrates that its level of polymorphism is comparable to those observed in other global populations.

HLA diversity and signatures of selection in the Maniq, a nomadic hunter-gatherer population in Southern Thailand - Helmut Schaschl; Tobias Herzog; Victoria Oberreiter; Wibhu Kutanan; Mattias Jakobsson; Maximilian Larena (Immunogenetics, 2025)
The Maniq, a small and isolated nomadic hunter-gatherer population from the rainforests of Southern Thailand, offer a unique context for investigating how demographic history, genetic drift, and pathogen-driven selection shape human leucocyte antigen (HLA) diversity. Using high-coverage whole-genome data from 21 individuals (12 unrelated), we genotyped HLA alleles with HLA-HD and T1K, identifying 32 alleles in classical and 14 in non-classical HLA genes. Although overall HLA diversity was comparatively low, a few alleles at each locus occurred at high frequency, mirroring patterns observed in other small, isolated populations. Principal-component analysis clustered the Maniq with other Austroasiatic-speaking Semang hunter-gatherers (Jehai, Kintaq) on the Malay Peninsula and, intriguingly, with the Austronesian-speaking Tao of Taiwan, indicating shared immunogenetic features across linguistic boundaries. Despite reduced diversity, multiple loci bore signatures of both long-term balancing and recent positive selection. Several SNPs under selection were in complete linkage disequilibrium with eQTLs known to influence responses to hepatitis B virus ( HBV ) and other pathogens, suggesting that pathogen-driven pressure—in particular HBV —may have contributed to recent HLA evolution in the Maniq. These findings provide critical insights into how demographic constraints and pathogen landscapes converge to shape HLA diversity and evolution. In light of increasing infectious disease burdens in indigenous communities, our results underscore the importance of studying small, isolated populations to better understand the adaptive significance of HLA genes.

Histocompatibility in Botryllus schlosseri and the origins of adaptive immunity - Anthony W. De Tomaso; Henry Rodriguez-Valbuena (Immunogenetics, 2025)
The basal chordate, Botryllus schlosseri , undergoes a natural transplantation reaction that is controlled by a single, highly polymorphic locus called the fuhc . The fuhc is one of the most polymorphic loci ever described, with most populations having hundreds of alleles, and up to a thousand found worldwide. Two individuals are compatible if they share one or both alleles, while those with no shared alleles are incompatible; thus, Botryllus uses a missing-self recognition strategy to discriminate between up to a thousand histocompatibility ligands. Remarkably, this discriminatory capability, which rivals that of vertebrate adaptive immunity, is carried out by germline-encoded receptors; thus, the mechanisms that establish and maintain this remarkable specificity are not understood. Multiple complete haplotypes of the fuhc locus have recently been sequenced, and at least seven genes with characteristics that suggest a role in allorecognition have been identified, including ligands, receptors, and intracellular proteins that likely organize and tune signal transduction complexes. This includes a new receptor family called the fester co-receptors ( FcoRs ) that encode ITIM and hemITAM domains, linking allorecognition in Botryllus to canonical immune transduction pathways. This review will summarize our current understanding and working hypotheses on the cellular and molecular mechanisms that control this innate, highly polymorphic allorecognition response, and how those may have been co-opted during the evolution of adaptive immunity.

Genome-wide diversity and MHC characterisation in a critically endangered freshwater turtle susceptible to disease - Holly V. Nelson; Luke Silver; Toby G. L. Kovacs; Elspeth A. McLennan; Arthur Georges; Jane L. DeGabriel; Carolyn J. Hogg; Katherine Belov (Immunogenetics, 2025)
Small, isolated populations are often vulnerable to increased inbreeding and genetic drift, both of which elevate the risk of extinction. The Bellinger River turtle ( Myuchelys georgesi ) is a critically endangered species endemic to a single river catchment in New South Wales, Australia. The only extant wild population, along with the breeding program, face significant threats from viral outbreaks, most notably a nidovirus outbreak in 2015 that led to a 90% population decline. To enhance our understanding of genomic characteristics in the species, including genome-wide and functional gene diversity, we re-sequenced, assembled, and analysed 31 re-sequenced genomes for pure M. georgesi ( N = 31). We manually annotated the major histocompatibility complex (MHC), identifying five MHC class I and ten MHC class II genes and investigated genetic diversity across both classes in M. georgesi . Our results showed that genome-wide diversity is critically low in pure M. georgesi , contexualised through comparison with opportunistically sampled backcross animals—offspring of F1 hybrids ( M. georgesi × Emydura macquarii ) backcrossed to pure M. georgesi ( N = 4). However, the variation observed within the core MHC region of pure M. georgesi , extending across scaffold 10, exceeded that of all other macrochromosomes. Additionally, no significant short-term changes in either genome-wide or immunogenetic diversity were detected following the 2015 nidovirus outbreak (before; N = 19, after; N = 12). Demographic history reconstructions indicated a sustained, long-term decline in effective population size since the last interglacial period, accompanied by more recent steep declines. These patterns suggested that prolonged isolation and reduced population size have significantly influenced the dynamics of genome-wide diversity. It is likely that contemporary stressors, including the recent nidovirus outbreak, are acting on an already genetically depleted population. This study offers new insights into genome-wide and immune gene diversity, including immune gene annotation data with broader implications for testudines. These findings provide crucial information to support future management strategies for the species.

Correction to: HCV immunodominant peptide mapping reveals unique HLA‑A* 02‑restricted signatures: insights for CD8+ T‑cell‑based vaccines and immunotherapies - Laura Cardoso Corrêa‑Dias; Ágata Lopes‑Ribeiro; Geovane Marques‑Ferreira; Letícia Gomes‑de‑Pontes; Thaiza Aline Pereira‑Santos; Erik Vinicius de Sousa Reis; Thaís de Fátima Silva Moraes; Olindo Assis Martins‑Filho; Edel Figueiredo Barbosa‑Stancioli; Flávio Guimarães da Fonseca; Jordana Grazziela Coelho‑dos‑Reis (Immunogenetics, 2025)

Allele co-segregation and haplotype diversity of MHC IIβ genes in the small-spotted catshark Scyliorhinus canicula - Alessia Rota; Ana Veríssimo; Arnaud Gaigher (Immunogenetics, 2025)
The major histocompatibility complex (MHC) constitutes a functionally relevant multigene family playing an essential role in the adaptive immune responses of jawed vertebrates, being directly involved in pathogen recognition. MHC diversity, driven by pathogen-mediated selection, is vital for species survival and is characterized by high genetic diversity in many taxa, namely at the sequence, allelic and haplotype levels. Chondrichthyans, the most basal jawed vertebrates with an adaptive immune system, exhibit a high diversity of MHC gene lineages conservatively organized in a compact region of the genome. Such genomic architecture suggests linkage among MHC genes, where alleles from different genes possibly co-segregate together. Such condition may have major implications on immune response, individual fitness and evolution. In this study, we examine MHC IIβ haplotype diversity in a model shark species, the small spotted catshark, Scyliorhinus canicula. Making use of pedigree data, we reconstructed MHC IIβ haplotypes to understand allele transmission from parent to offspring. Results indicate allele co-segregation consistent with tight linkage among MHC IIβ genes, suggesting the presence of functional stable haplotypes inherited from parents to offspring. The reconstructed haplotypes suggested extensive haplotype diversity characterized by variable allele numbers and allelic lineage composition, as well as marked allelic divergence, consistent with previous population-level data on this species. These findings underscore the complexity of MHC genetics (and of MHC evolution) in chondrichthyans. Accurate reconstruction of MHC haplotypes and assessment of its functional significance are crucial for better understanding adaptive immune responses and MHC evolutionary dynamics in chondrichthyans.

Phylogenetic and structural insights into the origin of C-type lectin Mincle in vertebrates - Taiki Ito; Carla Guenther; Eri Ishikawa; Takae Yabuki; Masamichi Nagae; Yoichiro Nakatani; Sho Yamasaki (Immunogenetics, 2025)
Our bodies are continuously exposed to injurious insults by infection and tissue damage, which are primarily sensed by innate immune receptors to maintain homeostasis. Among such receptors is macrophage-inducible C-type lectin (Mincle, gene symbol CLEC4E ), a member of the C-type lectin receptor (CLR) family, which functions as an immune sensor for both pathogens and damaged self. To monitor these injurious stimuli, Mincle recognizes disaccharide-based pathogen-derived glycolipids and monosaccharide-based intracellular metabolites, such as β-glucosylceramide. Mincle is well-conserved among mammals; however, there are questions that remain unclear, such as from which lower vertebrate did it arise and whether the original ligand was self or non-self. Here, we found homologues of Mincle and its signaling subunit Fc receptor γ chain (FcRγ) in lower vertebrates, such as reptiles, amphibians, and fishes. The crystal structure of a Mincle homologue revealed that fish Mincle possesses a narrower sugar-binding pocket than that of mammalian Mincle, and accommodates only monosaccharide moieties. These results suggest that Mincle may have evolved from a self-recognizing receptor, and its sugar-binding pocket widened during evolution, presumably to adapt to disaccharide-based glycolipids derived from life-threatening pathogens.

Kirsten Falk 1963-2024 - Hans-Georg Rammensee; Olaf Rötzschke (Immunogenetics, 2025)

Suppressed activation of the IRF7 and TLR9 by JAK2V617F gold nanoparticles - Berkay Tokcan; Esra Nur Demirtaş; Selçuk Sözer (Immunogenetics, 2025)
Philadelphia chromosome-negative myeloproliferative neoplasms (Ph-MPNs) are characterized by the overproduction of myeloid cells and a lack of response to cytokine signaling, along with genomic instability and the accumulation of nucleic acids in the cytoplasm. In this study, we investigated the effects of oligonucleotide-gold nanoparticle conjugates (ON-GNPs) targeting JAK2 or JAK2 V617F mRNAs on nucleic acid-sensing pathways in HEL, SET2, and K562 cell lines. We evaluated changes in gene expression related to TLR9 and cGAS/STING pathways, RAGE/TLR9 receptor dynamics, and inflammatory cytokine release over short-term (0.5–2 h) and long-term (24–72 h) exposures. Our results demonstrated that ON-GNPs transiently suppressed TLR9 , IRF7 , and NFKB1 expression during the short term, followed by significant upregulation after 24 h, persisting up to 72 h. Notably, JAK2 V617F-targeting ON-GNPs induced heightened IRF7 activation in HEL and SET2 cells after 24 h without affecting TLR9/RAGE expression. Additionally, IL-8 secretion increased in HEL and SET2 culture media after 72 h, correlating with interferon pathway activation. This study reveals that complementary ON-GNPs can modulate nucleic acid-sensing pathways, suppressing IL-8 and inflammatory signaling in the short term while inducing delayed activation of TLR9 and IRF7 in the presence of JAK2 V617F. These findings provide a promising foundation for developing ON-GNP-based therapeutic strategies to manage inflammation and disease progression in Ph-MPNs.

Primary regulatory T cell activator FOXP3 is present across Amphibia - Rebecca A. Clemons; Chase H. Smith; Kelly R. Zamudio (Immunogenetics, 2025)

Full-length mRNA sequencing resolves novel variation in 5′ UTR length for genes expressed during human CD4 T-cell activation - Cassandra R. Woolley; Julia H. Chariker; Eric C. Rouchka; Easton E. Ford; Elizabeth Hudson; Kamille M. Rasche; Caleb S. Whitley; Zachary Vanwinkle; Carolyn R. Casella; Melissa L. Smith; Thomas C. Mitchell (Immunogenetics, 2025)

HCV immunodominant peptide mapping reveals unique HLA-A*02-restricted signatures: insights for CD8+ T-cell-based vaccines and immunotherapies - Laura Cardoso Corrêa-Dias; Ágata Lopes-Ribeiro; Geovane Marques-Ferreira; Letícia Gomes-de-Pontes; Thaiza Aline Pereira-Santos; Erik Vinicius de Sousa Reis; Thaís de Fátima Silva Moraes; Olindo Assis Martins-Filho; Edel Figueiredo Barbosa-Stancioli; Flávio Guimarães da Fonseca; Jordana Grazziela Coelho-dos-Reis (Immunogenetics, 2025)

In silico functional analysis of the human, chimpanzee, and gorilla MHC-A repertoires - Griffin Kutler Dodd; Can Keşmir (Immunogenetics, 2025)
T cells recognize peptides displayed on the surface of cells on MHC molecules. Genetic variation in MHC genes alters their peptide-binding repertoire and thus influences the potential immune response generated against pathogens. Both gorillas and chimpanzees show reduced diversity at their MHC class I A (MHC-A) locus compared to humans, which has been suggested to be the result of a pathogen-mediated selective sweep. More specifically, gorillas lack A3 lineage alleles while chimpanzees seem to have lost the A2 lineage. While previous studies showed this using phylogenetic analysis, here, we take an in silico functional approach and use the peptide-MHC binding prediction software NetMHCpan to examine the peptide-binding repertoires of common human, chimpanzee, and gorilla MHC-A molecules. We find that both gorillas and chimpanzees lack the A02 peptide binding specificity (supertype) despite gorillas being expected to have this specificity since they kept the A2 lineage. Additionally, we show that human MHC molecules with the A02 specificity bind fewer virus-derived peptides than other MHC molecules. We also do not find differential presentation of self-peptides by the A02 supertype, making the purpose of maintaining this specificity in high frequencies in the human population unclear. Taken together, we hypothesize that poor presentation of viral peptides by A02 supertype MHC molecules could have resulted in a selective sweep in chimpanzees and/or gorillas, though we could not identify a specific virus that may have caused this sweep.

AMPed up immunity: 418 whole genomes reveal intraspecific diversity of koala antimicrobial peptides - Cleopatra Petrohilos; Emma Peel; Luke W. Silver; Katherine Belov; Carolyn J. Hogg (Immunogenetics, 2025)
Characterising functional diversity is a vital element to understanding a species’ immune function, yet many immunogenetic studies in non-model organisms tend to focus on only one or two gene families such as the major histocompatibility complex (MHC) or toll-like receptors (TLR). Another interesting component of the eukaryotic innate immune system is the antimicrobial peptides (AMPs). The two major groups of mammalian AMPs are cathelicidins and defensins, with the former having undergone species-specific expansions in marsupials. Here, we utilised data from 418 koala whole genomes to undertake the first comprehensive analysis of AMP diversity across a mammalian wildlife species’ range. Overall, allelic diversity was lower than other immune gene families such as MHC, suggesting that AMPs are more conserved, although balancing selection was observed in PhciDEFB12. Some non-synonymous SNPs in the active peptide are predicted to change AMP function through stop gains, change in structure, and increase in peptide charge. Copy number variants (CNVs) were observed in two defensins and one cathelicidin. Interestingly, the most common CNV was the duplication of PhciCATH5, a cathelicidin with activity against chlamydia, which was more common in the southern part of the species range than the north. AMP copy number is correlated with expression levels, so we hypothesise that there is a selective pressure from chlamydia for duplications in PhciCATH5. Future studies should use phenotypic metadata to assess the functional impacts of this gene duplication.

Uncovering selection pressures on the IRF gene family in bats’ immune system - Edgar G. Gutierrez; Jorge Ortega (Immunogenetics, 2025)

Syndecan-1: a key player in health and disease - Lara Diab; Sahar Al Kattar; Naim Oueini; Jihad Hawi; Antoine Chrabieh; Laura Dosh; Rosalyn Jurjus; Angelo Leone; Abdo Jurjus (Immunogenetics, 2025)

VaxOptiML: leveraging machine learning for accurate prediction of MHC-I and II epitopes for optimized cancer immunotherapy - Dhanushkumar T; Sunila B G; Sripad Rama Hebbar; Prasanna Kumar Selvam; Karthick Vasudevan (Immunogenetics, 2025)

Correction to: SNHG3 regulates NEIL3 via transcription factor E2F1 to mediate malignant proliferation of hepatocellular carcinoma - Fabiao Zhang; Jie Lu; Jian Yang; Qiqiang Dai; Xuefeng Du; Yongfu Xu; Caiming Zhang (Immunogenetics, 2025)

Novel polymorphic and copy number diversity in the antibody IGH locus of South African individuals - Alaine A. Marsden; Martin Corcoran; Gunilla Karlsson Hedestam; Nigel Garrett; Salim S. Abdool Karim; Penny L. Moore; Dale Kitchin; Lynn Morris; Cathrine Scheepers (Immunogenetics, 2025)
The heavy chain of an antibody is crucial for mediating antigen binding. IGHV genes, which partially encode the heavy chain of antibodies, exhibit vast genetic diversity largely through polymorphism and copy number variation (CNV). These genetic variations impact population-level expression levels. In this study, we analyzed expressed antibody transcriptomes and matched germline IGHV genes from donors from KwaZulu-Natal, South Africa. Amplicon NGS targeting germline IGHV sequences was performed on genomic DNA from 70 participants, eight of whom had matched datasets of expressed antibody transcriptomes. Germline IGHV sequencing identified 161 unique IGHV alleles, of which 32 were novel. A further 21 novel IGHV alleles were detected in the expressed transcriptomes of these donors. We also examined the datasets for CNV, uncovering gene duplications of 10 IGHV genes from germline sequencing and 33 genes in the expressed transcriptomes. Many of the IGHV gene duplications have not been described in other populations. This study expands our understanding of genetic differences in distinct populations and suggests the potential impact of genetic diversity on immune responses.

Spatial variation in toll-like receptor diversity in koala populations across their geographic distribution - Jian Cui; Kimberley C. Batley; Luke W. Silver; Elspeth A. McLennan; Carolyn J. Hogg; Katherine Belov (Immunogenetics, 2025)
The koala ( Phascolarctos cinereus ) is an iconic Australian species that is listed as endangered in the northern parts of its range due to loss of habitat, disease, and road deaths. Diseases contribute significantly to the decline of koala populations, primarily Chlamydia and koala retrovirus. The distribution of these diseases across the species’ range, however, is not even. Toll-like receptors (TLRs) play a crucial role in innate immunity by recognising and responding to various pathogens. Variations in TLR genes can influence an individual’s susceptibility or resistance to infectious diseases. The aim of this study was to identify koala TLR diversity across the east coast of Australia using 413 re-sequenced genomes at 30 × coverage. We identified 45 single-nucleotide polymorphisms (SNP) leading to 51 alleles within ten TLR genes. Our results show that the diversity of TLR genes in the koala forms four distinct genetic groups, which are consistent with the diversity of the koala major histocompatibility complex (MHC), another key immune gene family. The bioinformatics approach presented here has broad applicability to other threatened species with existing genomic resources.

Analysis of Complement Factor H gene polymorphisms and their association with clinical manifestations ofleptospirosis - Lazara Elena Santiesteban-Lores; Leonardo Moura Midon; ThirsaAlvares Franco; Luciano Marcondes de Oliveira; Sumire Hibi; Yosena Chiani; GdayllonCavalcante Meneses; Elizabeth De Francesco Daher; Denise Moraes Fonseca; Alessandra Pontillo; Lourdes Isaac (Immunogenetics, 2025)

Exploring the therapeutic potential of interleukin-6 receptor blockade in autoimmune diseases using drug target mendelian randomization - Jiaxin Li; Yalin Liu; Zheng Xiao; Chenyang Zang; Peihong Li; Bo Xiao; Luo Zhou (Immunogenetics, 2025)

A novel mutation in FNIP1 associated with a syndromic immunodeficiency and cardiomyopathy - Ilia Spivak; Atar Lev; Amos J. Simon; Ortal Barel; Ido Somekh; Raz Somech (Immunogenetics, 2025)
Genetic variants in Folli culin inte racting protein 1 (FNIP1) were recently discovered as monogenic causes for immunodeficiency and cardiomyopathy, with only a few patients diagnosed thus far. In this study, we describe a patient harboring a novel genetic variant in FNIP1 causing immunodeficiency with cardiac involvement. Clinical and immunological workups were performed. Genetic evaluation utilizing whole-exome sequencing (WES) and Sanger sequencing was conducted. The index patient (subject II-4) presented with hypertrophic cardiomyopathy, recurrent infections, and chronic diarrhea during infancy. Immune workup revealed agammaglobulinemia and a lack of B lymphocytes. Genetic evaluation identified a homozygous 13-bp duplication variant in FNIP1 (c.52_64dupGCGCCCGGCCGCG, p. Asp22GlyfsTer21) resulting in a frameshift in exon 1/18. She was treated with supplemental intravenous immunoglobulins (IVIg) with good control of sinopulmonary and gastrointestinal manifestations. Her sibling (subject II-1) had similar clinical features, along with dysmorphic facial features and hypotony, and succumbed to cardiogenic shock at the age of 2 months, prior to genetic evaluation. Diagnosis of novel immunodeficiencies promotes our understanding of the immune system, enabling genetic counseling as herein, and may assist in the development of novel medical therapies in the future. FNIP1 loss-of-function should be considered in patients presenting in infancy with cardiac manifestations along with agammaglobulinemia (and B-cell lymphopenia).

Epistatic effects of IGHG and FCGRIIB genes on the development of Alzheimer’s disease in African Americans - Janardan P. Pandey; Paul J. Nietert; Aryan M. Namboodiri; David A. Bennett; Lisa L. Barnes (Immunogenetics, 2025)
Genome-wide association studies (GWAS) of Alzheimer’s disease (AD) have identified a large number of susceptibility genes, but most of AD heritability remains unexplained, implying the existence of additional genes. Furthermore, the majority of the GWAS have been conducted in people of European descent, and the genes important for AD susceptibility in people of African descent have been underexplored. In this hypothesis-generating prospective cohort study, we genotyped 191 African Americans (AAs) from three longitudinal cohorts on aging for the IgG3 allotype GM6, which is expressed exclusively in people of African descent, and assessed its interaction with IGHG , FCGRIIB , and HLA-DRB1 genes. Cox proportional hazards modeling showed that GM6 by itself was not significantly associated with AD development. However, there was evidence of epistatic interaction: The risk of developing AD associated with GM6 positivity was significantly different ( p = 0.0098) in non-GM17/GM17 participants compared with GM 17/GM17 participants. Specifically, in non-GM17/GM17 participants, the risk of AD was over fourfold higher in GM6-positive participants compared with GM 6-negative participants (HR = 4.63). Similarly, risk of developing AD associated with GM6 positivity was marginally different in non-FCGRIIB TT participants compared with FCGRIIB TT participants. In non-FCGRIIB TT participants, the risk of developing AD was over twofold higher in GM6-positive participants compared with GM6-negative participants (HR = 2.44). This is the first report suggesting that immunoglobulin GM allotypes might play a role in AD etiology among AAs; however, since this was largely a hypothesis-generating study, replication in larger cohorts would be required to confirm this finding.

Evolutionary diversity of CXCL16-CXCR6: Convergent substitutions and recurrent gene loss in sauropsids - Buddhabhushan Girish Salve; Sandhya Sharma; Nagarjun Vijay (Immunogenetics, 2024)

Using bioinformatics to investigate functional diversity: a case study of MHC diversity in koalas - Luke W. Silver; Elspeth A. McLennan; Julian Beaman; Karen Burke da Silva; Peter Timms; Carolyn J. Hogg; Katherine Belov (Immunogenetics, 2024)
Conservation genomics can greatly improve conservation outcomes of threatened populations, including those impacted by disease. Understanding diversity within immune gene families, including the major histocompatibility complex (MHC) and toll-like receptors (TLR), is important due to the role they play in disease resilience and susceptibility. With recent advancements in sequencing technologies and bioinformatic tools, the cost of generating high-quality sequence data has significantly decreased and made it possible to investigate diversity across entire gene families in large numbers of individuals compared to investigating only a few genes or a few populations previously. Here, we use the koala as a case study for investigating functional diversity across populations. We utilised previous target enrichment data and 438 whole genomes to firstly, determine the level of sequencing depth required to investigate MHC diversity and, secondly, determine the current level of diversity in MHC genes in koala populations. We determined for low complexity, conserved genes such as TLR genes 10 × sequencing depth is sufficient to reliably genotype more than 90% of variants, whereas for complex genes such as the MHC greater than 20 × and preferably 30 × sequencing depth is required. We used whole genome data to identify 270 biallelic SNPs across 24 MHC genes as well as copy number variation (CNV) within class I and class II genes and conduct supertype analysis. Overall, we have provided a bioinformatic workflow for investigating variation in a complex immune gene family from whole genome sequencing data and determined current levels of diversity within koala MHC genes.

A genome assembly and transcriptome atlas of the inbred Babraham pig to illuminate porcine immunogenetic variation - John C. Schwartz; Colin P. Farrell; Graham Freimanis; Andrew K. Sewell; John D. Phillips; John A. Hammond (Immunogenetics, 2024)
The inbred Babraham pig serves as a valuable biomedical model for research due to its high level of homozygosity, including in the major histocompatibility complex (MHC) loci and likely other important immune-related gene complexes, which are generally highly diverse in outbred populations. As the ability to control for this diversity using inbred organisms is of great utility, we sought to improve this resource by generating a long-read whole genome assembly and transcriptome atlas of a Babraham pig. The genome was de novo assembled using PacBio long reads and error-corrected using Illumina short reads. Assembled contigs were then mapped to the porcine reference assembly, Sscrofa11.1, to generate chromosome-level scaffolds. The resulting TPI_Babraham_pig_v1 assembly is nearly as contiguous as Sscrofa11.1 with a contig N50 of 34.95 Mb and contig L50 of 23. The remaining sequence gaps are generally the result of poor assembly across large and highly repetitive regions such as the centromeres and tandemly duplicated gene families, including immune-related gene complexes, that often vary in gene content between haplotypes. We also further confirm homozygosity across the Babraham MHC and characterize the allele content and tissue expression of several other immune-related gene complexes, including the antibody and T cell receptor loci, the natural killer complex, and the leukocyte receptor complex. The Babraham pig genome assembly provides an alternate highly contiguous porcine genome assembly as a resource for the livestock genomics community. The assembly will also aid biomedical and veterinary research that utilizes this animal model such as when controlling for genetic variation is critical.

Sequence variants underlying severe combined immunodeficiency and leukocyte adhesion deficiency type 1 in six consanguineous families - Hajra Fayyaz; Atteaya Zaman; Nighat Haider; Rehmana Waris; Muhammad Hussain; Syed Irfan Raza; Wasim Ahmad; Imran Ullah (Immunogenetics, 2024)

Potential contribution of gut microbiota in the development of autoantibodies in T1D children carrying HLA-DRB1/DQB1 risk alleles: an experimental and in silico analysis - Ata Shirizadeh; Zahra Razavi; Vahid Saeedi; Mahdi Behzad; Javad Faradmal; Ghasem Solgi (Immunogenetics, 2024)

NOD alleles at Idd1 and Idd2 loci drive exocrine pancreatic inflammation - Laurence Caron; Daria Vdovenko; Félix Lombard-Vadnais; Sylvie Lesage (Immunogenetics, 2024)

The effect of circulating cytokines on the risk of systemic lupus erythematosus: Mendelian randomization and observational study - Dan Xue; Yu Qian; Xiao Tu; Mu He; Fengling Xing; Yunqing Ren; Chengda Yuan (Immunogenetics, 2024)

The characteristic of HLA-A, HLA-B, HLA-C, HLA-DRB1, HLA-DRB3/4/5, HLA-DQA1, HLA-DQB1, HLA-DPA1, and HLA-DPB1 alleles in Zhejiang Han population - Sudan Tao; Xuan You; Nanying Chen; Lina Dong; Shuoxian Zhao; Yizhen He; Wei Zhang; Faming Zhu (Immunogenetics, 2024)

Decoding the genetic landscape of juvenile dermatomyositis: insights from phosphorylation-associated single nucleotide polymorphisms - Huan Zhang; Zhentao Zhang; Kedi Fan; Hongru Chen; Yufan Guo; Xingbo Mo (Immunogenetics, 2024)

Bioinformatic analysis predicts the regulatory function of noncoding SNPs associated with Long COVID-19 syndrome - Amit K. Maiti (Immunogenetics, 2024)

The sufficiency of genetic diagnosis in managing patients with inborn errors of immunity during prenatal care and childbearing - Negin Salemi; Shima Bakhshesh; Amir Bahreini; Rasoul Salehi; Aryana Zamanifar; Fariba Dehghan; Roya Sherkat (Immunogenetics, 2024)

A possible role of lncRNA MEG3 and lncRNA MAFG-AS1 on miRNA 147-b in the pathogenesis of Behcet’s disease - Shimaa Abobakr; Olfat Shaker; Mohamed Tharwat Hegazy; Ayman Mohamed Hany (Immunogenetics, 2024)
Behcet’s disease (BD) is a multisystem disease with altered Toll-like receptors (TLRs) on macrophages. Long noncoding RNA Maternally expressed gene 3 (lncRNA MEG3) and lncRNA Musculoaponeurotic fibrosarcoma oncogene family, protein G antisense 1 (MAFG-AS1) are regulators of microRNA (miRNA) 147-b, which is induced upon TLR stimulation. We included fifty BD patients, and fifty age and sex-matched controls. Real-time polymerase chain reaction (PCR) was used to measure the expression levels of serum lncRNA MEG3, lncRNA MAFG-AS1, and miRNA 147-b. LncRNA MEG3 and lncRNA MAFG-AS1 were significantly downregulated while miRNA 147-b was significantly upregulated in the BD patients' serum compared to the controls with p -value <0.001. Receiver operation characteristics (ROC) curve analysis revealed that the three biomarkers can discriminate between BD and control subjects with 76%, 100%, and 70% sensitivity respectively, and 100% specificity for all of them. There was a lower expression level of lnc RNA MEG3 among patients who had new eye involvement in the last month in comparison to those without new eye involvement ( p -value=0.017). So, LncRNA MEG3, lncRNA MAFG-AS1, and miRNA147-b are promising diagnostic markers and therapeutic targets for BD patients. LncRNA MEG3 can be used as a predictor for new BD ocular involvement.

Associations between immune cell traits and autoimmune thyroid diseases: a bidirectional two-sample mendelian randomization study - ZheXu Cao; JiangSheng Huang; Xia Long (Immunogenetics, 2024)

Dog leukocyte antigen genotyping across class I and class II genes in beagle dogs as laboratory animals - Hiroya Konno; Jiro Miyamae; Hiroko Kataoka; Makoto Akai; Hiroaki Miida; Yoshimi Tsuchiya (Immunogenetics, 2024)

HLA alleles, haplotypes frequencies, and their association with hematological disorders: a report from 1550 families whose patients underwent allogeneic bone marrow transplantation in Egypt - Yasser ElNahass; Nourhan Mekky; Nabil M. Abdelfattah; Raafat Abdelfattah; Mohamed Samra; Omar A. Fahmy; Gamal Fathy; Wafaa Elmetnawy; Salwa Sabet; Heba Bassiouny; Heba Nader; Alaa ElHaddad; et al. (Immunogenetics, 2024)

B-cells absence in patients diagnosed as inborn errors of immunity: a registry-based study - Razieh Khoshnevisan; Shakiba Hassanzadeh; Christoph Klein; Meino Rohlfs; Bodo Grimbacher; Newsha Molavi; Aryana Zamanifar; Ali Khoshnevisan; Mahbube Jafari; Bahram Bagherpour; Mahdiyeh Behnam; Somayeh Najafi; et al. (Immunogenetics, 2024)

Determination of HLA class II risk alleles and prediction of self/non-self-epitopes contributing Hashimoto’s thyroiditis in a group of Iranian patients - Ata Shirizadeh; Shiva Borzouei; Zahra Razavi; Amir Taherkhani; Javad Faradmal; Ghasem Solgi (Immunogenetics, 2024)

Immunoglobulin genes and severity of COVID-19 - Daniel Vázquez-Coto; Christine Kimball; Guillermo M. Albaiceta; Laura Amado-Rodríguez; Marta García-Clemente; Juan Gómez; Eliecer Coto; Janardan P. Pandey (Immunogenetics, 2024)
There is tremendous interindividual and interracial variability in the outcome of SARS-CoV-2 infection, suggesting the involvement of host genetic factors. Here, we investigated whether IgG allotypes GM (γ marker) 3 and GM 17, genetic markers of IgG1, contributed to the severity of COVID-19. IgG1 plays a pivotal role in response against SARS-CoV-2 infection. We also investigated whether these GM alleles synergistically/epistatically with IGHG3 and FCGR2A alleles—which have been previously implicated in COVID-19—modulated the extent of COVID-19 severity. The study population consisted of 316 COVID-19 patients who needed treatment in the intensive care unit of Hospital Universitario Central de Asturias. All individuals were genotyped for GM 3/17, IGHG3 hinge length, and FCGR2A rs1801274 A/G polymorphisms. Among the 316 critical patients, there were 86 deaths. The risk of death among critical patients was significantly higher in subjects with GM 17 (IgG1) and short hinge length (IgG3). GM 17-carriers were at almost three-fold higher risk of death than non-carriers ( p < 0.001; OR = 2.86, CI 1.58–5.16). Subjects with short hinge length of IgG3 had a two-fold higher risk of death than those with medium hinge length ( p = 0.01; OR = 2.16, CI 1.19–3.90). GM 3/3 and IGHG3 (MM) genotypes were less frequent among death vs. survivors (9% vs 36%, p < 0.001) and associated with protective effect (OR = 0.18, 95% CI = 0.08–0.39). This is the first report implicating IgG1 allotypes in COVID-19-spurred death. It needs to be replicated in an independent study population.

A novel hemizygous CD40L mutation of X-linked hyper IgM syndromes and compound heterozygous DOCK8 mutations of hyper IgE syndromes in two Chinese families - Mingzhen Guo; Yuanxuan Ma; Kangxi Cai; Xiuxiang Liu; Wenmiao Liu; Fengqi Wang; Niyan Qu; Shiguo Liu (Immunogenetics, 2024)

HLA class I NK-epitopes and KIR diversities in patients with multiple myeloma - Nicky A. Beelen; Stefan J. J. Molenbroeck; Lisette Groeneveld; Christien E. Voorter; Gerard M. J. Bos; Lotte Wieten (Immunogenetics, 2024)
Multiple myeloma (MM) is a hematological malignancy caused by the clonal expansion of malignant plasma cells in the bone marrow. Myeloma cells are susceptible to killing by natural killer (NK) cells, but NK cells fail to control disease progression, suggesting immunosuppression. The activation threshold of NK-effector function is regulated by interaction between KIRs and self-HLA class I, during a process called “education” to ensure self-tolerance. NK cells can respond to diseased cells based on the absence of HLA class I expression (“Missing-self” hypothesis). The HLA and KIR repertoire is extremely diverse; thus, the present study aimed to characterize potential variances in genotypic composition of HLA Class I NK-epitopes and KIRs between MM patients and healthy controls. Genotypic expression of KIR and HLA (HLA-C group-C1/C2 and Bw4 motifs (including HLA-A*23, A*24, A*32) were analyzed in 172 MM patients and 195 healthy controls. Compared to healthy controls, we did not observe specific KIR genes or genotypes, or HLA NK-epitopes with higher prevalence among MM patients. The presence of all three HLA NK-epitopes (C1 + C2 + Bw4 + ) was not associated with MM occurrence. However, MM patients were more likely to be C1 - /C2 + /Bw4 + ( p = 0.049, OR 1.996). In line with this, there was a trend of increased genetic co-occurrence of Bw4 and KIR3DL1 in MM patients ( p = 0.05, OR 1.557). Furthermore, MM patients were more likely to genetically express both C2/KIR2DL1 and Bw4/KIR3DL1 ( p = 0.019, OR 2.453). Our results reveal an HLA NK-epitope combination that is associated with the occurrence of MM. No specific KIR genotypes were associated with MM.

Lack of Syndecan-1 promotes the pathogenesis of experimental rheumatoid arthritis - Rosalyn Jurjus; Laura Dosh; Rima Farhat; Tatiana Daccache; Jad El Masri; Maya Ghazi; Jihad Hawi; Angelo Leone; Abdo Jurjus (Immunogenetics, 2024)

Evolutionary divergence of TLR9 through ancestral sequence reconstruction - Manisha Ghosh; Surajit Basak; Shanta Dutta (Immunogenetics, 2024)

Causal effect of interleukin (IL)-6 on blood pressure and hypertension: A mendelian randomization study - Ou Wu; Ya Wu; Xingyu Zhang; Wei Liu; Hu Zhang; Saber Khederzadeh; Xi Lu; Xiao-Wei Zhu (Immunogenetics, 2024)

Resolving unknown nucleotides in the IPD-IMGT/HLA database by extended and full-length sequencing of HLA class I and II alleles - Christina E. M. Voorter; Mathijs Groeneweg; Timo I. Olieslagers; Ingrid Fae; Gottfried F. Fischer; Marco Andreani; Maria Troiano; Blanka Vidan-Jeras; Sendi Montanic; Bouke G. Hepkema; Laura B. Bungener; Marcel G. J. Tilanus; et al. (Immunogenetics, 2024)
In the past, identification of HLA alleles was limited to sequencing the region of the gene coding for the peptide binding groove, resulting in a lack of sequence information in the HLA database, challenging HLA allele assignment software programs. We investigated full-length sequences of 19 HLA class I and 7 HLA class II alleles, and we extended another 47 HLA class I alleles with sequences of 5′ and 3′ UTR regions that were all not yet available in the IPD-IMGT/HLA database. We resolved 8638 unknown nucleotides in the coding sequence of HLA class I and 2139 of HLA class II. Furthermore, with full-length sequencing of the 26 alleles, more than 90 kb of sequence information was added to the non-coding sequences, whereas extension of the 47 alleles resulted in the addition of 5.5 kb unknown nucleotides to the 5′ UTR and > 31.7 kb to the 3′ UTR region. With this information, some interesting features were observed, like possible recombination events and lineage evolutionary origins. The continuing increase in the availability of full-length sequences in the HLA database will enable the identification of the evolutionary origin and will help the community to improve the alignment and assignment accuracy of HLA alleles.

Concise review: The heterogenous roles of BATF3 in cancer oncogenesis and dendritic cells and T cells differentiation and function considering the importance of BATF3-dependent dendritic cells - Reza Dabbaghipour; Elham Ahmadi; Mona Entezam; Omid Rahbar Farzam; Sepideh Sohrabi; Sajjad Jamali; Ali Saber Sichani; Hadi Paydar; Behzad Baradaran (Immunogenetics, 2024)

Regulation of genes involved in the metabolic adaptation of murine microglial cells in response to elevated HIF-1α mediated activation - Ida Florance; Seenivasan Ramasubbu (Immunogenetics, 2024)

Determination for KIR genotype and allele copy number via real-time quantitative PCR method - Sudan Tao; Xuan You; Jielin Wang; Wei Zhang; Ji He; Faming Zhu (Immunogenetics, 2024)

Costimulatory receptors in the channel catfish: CD28 family members and their ligands - Sylvie M. A. Quiniou; Eva Bengtén; Pierre Boudinot (Immunogenetics, 2024)

The impact of long COVID on health-related quality of life in patients 6 months after discharge with severe COVID-19 - Seyedeh Mahdieh Namayandeh; Moslem Basti; Sara Jambarsang; Seyed Mojtaba Yassini Ardekani (Immunogenetics, 2024)

Patterns of evolution in MHC class II DQA and DQB exon 2 genes of Alpine mountain hares, Lepus timidus varronis, and sympatric and parapatric brown hares, L. europaeus, from Switzerland - A. Awadi; H. Ben Slimen; S. Smith; M. Makni; F. Suchentrunk (Immunogenetics, 2024)

The COVID-19 inflammation and high mortality mechanism trigger - Samuel Stróż; Piotr Kosiorek; Anna Stasiak-Barmuta (Immunogenetics, 2024)

A novel missense mutation in the AIRE gene underlying autoimmune polyglandular syndrome type 1 - Susana Vitozzi; Silvia Graciela Correa; Alejandro Lozano; Eduardo Jorge Fernández; Rodrigo Quiroga (Immunogenetics, 2024)

Investigating associations between HLA DQA1 ~ DQB1 haplotypes, H. pylori infection, metaplasia, and anti-CagA IgA seropositivity in a Turkish gastritis cohort - Mukaddes Colakogullari; Lokman Karatas; Zeynep Tatar (Immunogenetics, 2024)

Immunogenetics, sylvatic plague and its vectors: insights from the pathogen reservoir Mastomys natalensis in Tanzania - Lavinia Haikukutu; Japhet R. Lyaku; Charles M. Lyimo; Seth J. Eiseb; Rhodes H. Makundi; Ayodeji Olayemi; Kerstin Wilhelm; Nadine Müller-Klein; Dominik W. Schmid; Ramona Fleischer; Simone Sommer (Immunogenetics, 2023)
Yersinia pestis is a historically important vector-borne pathogen causing plague in humans and other mammals. Contemporary zoonotic infections with Y. pestis still occur in sub-Saharan Africa, including Tanzania and Madagascar, but receive relatively little attention. Thus, the role of wildlife reservoirs in maintaining sylvatic plague and spillover risks to humans is largely unknown. The multimammate rodent Mastomys natalensis is the most abundant and widespread rodent in peri-domestic areas in Tanzania, where it plays a major role as a Y. pestis reservoir in endemic foci. Yet, how M. natalensis ’ immunogenetics contributes to the maintenance of plague has not been investigated to date. Here, we surveyed wild M. natalensis for Y. pestis vectors, i.e., fleas, and tested for the presence of antibodies against Y. pestis using enzyme-linked immunosorbent assays (ELISA) in areas known to be endemic or without previous records of Y. pestis in Tanzania. We characterized the allelic and functional (i.e., supertype) diversity of the major histocompatibility complex (MHC class II) of M. natalensis and investigated links to Y. pestis vectors and infections. We detected antibodies against Y. pestis in rodents inhabiting both endemic areas and areas considered non-endemic. Of the 111 nucleotide MHC alleles, only DRB*016 was associated with an increased infestation with the flea Xenopsylla . Surprisingly, we found no link between MHC alleles or supertypes and antibodies of Y. pestis . Our findings hint, however, at local adaptations towards Y. pestis vectors, an observation that more exhaustive sampling could unwind in the future.

Macroevolution of avian T cell receptor C segments using genomic data - Chunhong Liang; Lin Sun; Ying Zhu; Ayong Zhao; Hongyi Liu; Ke He (Immunogenetics, 2023)

The KIR2DL1 intermediate upstream element participates in gene activation - Paul W. Wright; Hongchuan Li; Md Ahasanur Rahman; Erik M. Anderson; Megan Karwan; Jeffrey Carrell; Stephen K. Anderson (Immunogenetics, 2023)
The human KIR genes encode a family of class I MHC receptors that are expressed on subsets of NK cells. The expression of KIR proteins is controlled by a stochastic process, and competition between sense and antisense promoter elements has been suggested to program the variegated expression of these genes. Previous studies have demonstrated distinct roles of distal, intermediate, and proximal sense promoter/enhancer elements in gene activation and expression. Conversely, proximal and intronic antisense promoter transcripts have been associated with gene silencing at different stages of NK cell development. In the current study, we examine the effect of intermediate promoter deletion on KIR2DL1 expression in the YTS cell line. Homozygous deletion of the KIR2DL1 intermediate element did not affect proximal promoter activity but resulted in increased detection of upstream transcripts. No significant changes in alternative mRNA splicing or expression levels of KIR2DL1 protein were observed. However, intermediate element deletion was associated with a reduced frequency of gene activation by 5-azacytidine. Taken together, these results indicate that the intermediate element is not an enhancer required for KIR expression; however, it is required for the efficient activation of the gene.

Comparative genomics of the T cell receptor μ locus in marsupials and monotremes - K. A. Morrissey; M. R. Stammnitz; E. Murchison; R. D. Miller (Immunogenetics, 2023)

Genomic view of the origins of cell-mediated immunity - Morgan E. Janes; Allison Kinlein; Martin F. Flajnik; Louis Du Pasquier; Yuko Ohta (Immunogenetics, 2023)

Correlation between human leukocyte antigen ligands and killer cell immunoglobulin-like receptors in aplastic anemia patients from Shaanxi Han - Tianju Wang; Jun Qi; Manni Wang; Hua Xu; Junhua Wu; Lixia Shang; Le Chen; Yuhui Li (Immunogenetics, 2023)

Ancient fish lineages illuminate toll-like receptor diversification in early vertebrate evolution - Kara B. Carlson; Cameron Nguyen; Dustin J. Wcisel; Jeffrey A. Yoder; Alex Dornburg (Immunogenetics, 2023)

Increased circulating Th17 cell populations in patients with pancreatic ductal adenocarcinoma - Imteyaz Ahmad Khan; Nidhi Singh; Deepak Gunjan; Srikant Gopi; Nihar Ranjan Dash; Surabhi Gupta; Anoop Saraya (Immunogenetics, 2023)

Prof. Dr. Jan Klein (1936-2023) - Ronald Bontrop; Martin Flajnik; Colm S. O’Huigin; Masanori Kasahara (Immunogenetics, 2023)

Factors regulating the differences in frequency of infiltration of Th17 and Treg of the blood–brain barrier - Norwin Kubick; Marzena Lazarczyk; Nina Strzałkowska; Anna Charuta; Jarosław Olav Horbańczuk; Mariusz Sacharczuk; Michel Edwar Mickael (Immunogenetics, 2023)

The minor chicken class I gene BF1 is deleted between short imperfect direct repeats in the B14 and typical B15 major histocompatibility complex (MHC) haplotypes - Nicolas I. E. Rocos; Felicity J. Coulter; Thomas C. J. Tan; Jim Kaufman (Immunogenetics, 2023)
The chicken major histocompatibility complex (MHC, also known as the BF-BL region of the B locus) is notably small and simple with few genes, most of which are involved in antigen processing and presentation. There are two classical class I genes, of which only BF2 is well and systemically expressed as the major ligand for cytotoxic T lymphocytes (CTLs). The other class I gene, BF1, is believed to be primarily a natural killer (NK) cell ligand. Among most standard chicken MHC haplotypes examined in detail, BF1 is expressed tenfold less than BF2 at the RNA level due to defects in the promoter or in a splice site. However, in the B14 and typical B15 haplotypes, BF1 RNA was not detected, and here, we show that a deletion between imperfect 32 nucleotide direct repeats has removed the BF1 gene entirely. The phenotypic effects of not having a BF1 gene (particularly on resistance to infectious pathogens) have not been systematically explored, but such deletions between short direct repeats are also found in some BF1 promoters and in the 5′ untranslated region (5′UTR) of some BG genes found in the BG region of the B locus. Despite the opposite transcriptional orientation of homologous genes in the chicken MHC, which might prevent the loss of key genes from a minimal essential MHC, it appears that small direct repeats can still lead to deletion.

Dysregulated PD-L2 is correlated with disease activity and inflammation in rheumatoid arthritis - Jian Xiong; Jie Yang; Yuling Sun; Yachun Chen; Yundi Guo; Cuiping Liu; Jing Sun (Immunogenetics, 2023)

Correction to: Evaluation of miRNA-16–2-3P, miRNA-618 levels and their diagnostic and prognostic value in the regulation of immune response during SARS Cov-2 infection - Nourelhoda E. Hassan; Walaa A. Moselhy; Ehab B. Eldomany; Emad Farah Mohamad Kholef (Immunogenetics, 2023)

Prognostic value of the WT-1 gene combined with recurrent cytogenetic genes in acute myeloid leukemia - Qing Zhang; Linlin Liu; Haotian Yan; Xiyang Ren; Mei Zhou; Shudao Xiong; Huiping Wang; Qianshan Tao; Zhimin Zhai (Immunogenetics, 2023)

Complement component C1q is an immunological rheostat that regulates Fc:Fc$$γ$$R interactions - Edward C. So; Hua Zhou; Ariana Greenwell; Erin E. Burch; Yaping Ji; Emmanuel Y. Mérigeon; Henrik S. Olsen; Søren M. Bentzen; David S. Block; Xiaoyu Zhang; Scott E. Strome (Immunogenetics, 2023)

Immunological assessment of a patient with Omenn syndrome resulting from compound heterozygous mutations in the RAG1 gene - Wenjun Mou; Zixin Yang; Xiaojiao Wang; Mingyan Hei; Yajuan Wang; Jingang Gui (Immunogenetics, 2023)

Evaluation of miRNA-16–2-3P, miRNA-618 levels and their diagnostic and prognostic value in the regulation of immune response during SARS Cov-2 infection - Nourelhoda E. Hassan; Walaa A. Moselhy; Ehab B. Eldomany; Emad Farah Mohamad Kholef (Immunogenetics, 2023)
Following the announcement of the pandemic of COVID-19 in December 2019, several studies focused on how to early predict the severity of the disease in symptomatic and asymptomatic patients. Many cytokines including interleukin-6, interleukin-8, and tumor necrotic factors have been concluded as strong indicators for COVID-19 infection. Additionally, miRNAs have been associated with dysregulation in the immune system. The aim of this study are the following: (1) to estimate the level of miRNA-16–2-3P, miRNA-618, IL-8, IL-1β as predictors for SARS-CoV-2 complications in PCR negative and positive patients; (2) to assess the biological role and effect of these miRNAs on SARS-CoV-2 pathogenicity. Our study showed that the level of IL-1β had been significantly associated with patient who need hospitalization, also the alteration of the level of miRNA-16–2-3P, miRNA-618 is positively correlated with the admission of these patients and influence the outcomes of SARS-cov-2 infection. Measurement of miRNA-16–2-3P, miRNA-618, IL-1β could be a good predictor of COVID-19 patient outcome. However the measurement of IL-8 levels during immune responses in the admitted and in ICU patients could have a prognostic value.

Germline-enforced enrichment for charged amino acids in TCR beta chain (TCRβ) complementarity determining region 3 (CDR-B3) alters T cell development, repertoire content, and antigen recognition - Michael Levinson; Mohamed Khass; Peter D. Burrows; Harry W Schroeder (Immunogenetics, 2023)

Evolution of immunogenetic components encoding ultralong CDR H3 - Jeannine A. Ott; Christian Mitchell; Morgan Sheppard; Thad C. Deiss; J. M. Cody Horton; Jeremy K. Haakenson; Ruiqi Huang; Abigail R. Kelley; Brian W. Davis; James N. Derr; Vaughn V. Smider; Michael F. Criscitiello (Immunogenetics, 2023)

Characterization and genetic diversity of MHC class II DRB genes in the Arabian camel (Camelus dromedarius) - Mohamed Habib Yahyaoui (Immunogenetics, 2023)

Immunogenetics special issue 2023: Immunogenetics of infectious disease - Paul J. Norman (Immunogenetics, 2023)

Impact of high human genetic diversity in Africa on immunogenicity and efficacy of RTS,S/AS01 vaccine - Stephen Tukwasibwe; Gerald Mboowa; Ivan Sserwadda; Joaniter I. Nankabirwa; Emmanuel Arinaitwe; Isaac Ssewanyana; Yoweri Taremwa; Gerald Tumusiime; Moses R. Kamya; Prasanna Jagannathan; Annettee Nakimuli (Immunogenetics, 2023)

Correction to: The immunogenetics of COVID-19 - Anshika Srivastava; Jill A. Hollenbach (Immunogenetics, 2023)

Role of T cells in severe COVID-19 disease, protection, and long term immunity - Julia Maret Hermens; Can Kesmir (Immunogenetics, 2023)
Infection with SARS-CoV-2 causes wide range of disease severities from asymptomatic to life-threatening disease. Understanding the contribution of immunological traits in immunity against SARS-CoV-2 and in protection against severe COVID-19 could result in effective measures to prevent development of severe disease. While the role of cytokines and antibodies has been thoroughly studied, this is not the case for T cells. In this review, the association between T cells and COVID-19 disease severity and protection upon reexposure is discussed. While infiltration of overactivated cytotoxic T cells might be harmful in the infected tissue, fast responding T cells are important in the protection against severe COVID-19. This protection could even be viable in the long term as long-living memory T cells seem to be stabilized and mutations do not appear to have a large impact on T cell responses. Thus, after vaccination and infections, memory T cells should be able to help prevent onset of severe disease for most cases. Considering this, it would be useful to add N or M proteins in vaccinations, alongside the S protein which is currently used, as this results in a broader T cell response.

Evolution of SARS-CoV-2-specific CD4+ T cell epitopes - Marina Brand; Can Keşmir (Immunogenetics, 2023)
Vaccination clearly decreases coronavirus disease 2019 (COVID-19) mortality; however, they also impose selection pressure on the virus, which promotes the evolution of immune escape variants. For example, despite the high vaccination level in especially Western countries, the Omicron variant caused millions of breakthrough infections, suggesting that the highly mutated spike protein in the Omicron variant can escape antibody immunity much more efficiently than the other variants of concern (VOCs). In this study, we investigated the resistance/susceptibility of T helper cell responses that are necessary for generating efficient long-lasting antibody immunity, in several VOCs. By predicting T helper cell epitopes on the spike protein for most common HLA-DRB1 alleles worldwide, we found that although most of high frequency HLA-DRB1 alleles have several potential T helper cell epitopes, few alleles like HLA-DRB1 13:01 and 11:01 are not predicted to have any significant T helper cell responses after vaccination. Using these predictions, a population based on realistic human leukocyte antigen-II (HLA-II) frequencies were simulated to visualize the T helper cell immunity on the population level. While a small fraction of this population had alarmingly little predicted CD4 T cell epitopes, the majority had several epitopes that should be enough to generate efficient B cell responses. Moreover, we show that VOC spike mutations hardly affect T helper epitopes and mainly occur in other residues of the spike protein. These results suggest that lack of long-lasting antibody responses is not likely due to loss of T helper cell epitopes in new VOCs.

Innate receptors modulating adaptive T cell responses: KIR-HLA interactions and T cell-mediated control of chronic viral infections - Laura Mora-Bitria; Becca Asquith (Immunogenetics, 2023)
Killer-cell immunoglobulin-like receptors (KIRs) are mainly expressed on natural killer (NK) cells and are key regulators of innate immune responses. NK cells are the first responders in the face of infection and help promote placentation during pregnancy; the importance of KIRs in these NK-mediated processes is well-established. However, mounting evidence suggests that KIRs also have a prominent and long-lasting effect on the adaptive immune system. Here, we review the evidence for the impact of KIRs on T cell responses with a focus on the clinical significance of this interaction.

Comparison between qPCR and RNA-seq reveals challenges of quantifying HLA expression - Vitor R. C. Aguiar; Erick C. Castelli; Richard M. Single; Arman Bashirova; Veron Ramsuran; Smita Kulkarni; Danillo G. Augusto; Maureen P. Martin; Maria Gutierrez-Arcelus; Mary Carrington; Diogo Meyer (Immunogenetics, 2023)

The impact of HLA polymorphism on herpesvirus infection and disease - William H. Palmer; Paul J. Norman (Immunogenetics, 2023)
Human Leukocyte Antigens (HLA) are cell surface molecules, central in coordinating innate and adaptive immune responses, that are targets of strong diversifying natural selection by pathogens. Of these pathogens, human herpesviruses have a uniquely ancient relationship with our species, where coevolution likely has reciprocating impact on HLA and viral genomic diversity. Consistent with this notion, genetic variation at multiple HLA loci is strongly associated with modulating immunity to herpesvirus infection. Here, we synthesize published genetic associations of HLA with herpesvirus infection and disease, both from case/control and genome-wide association studies. We analyze genetic associations across the eight human herpesviruses and identify HLA alleles that are associated with diverse herpesvirus-related phenotypes. We find that whereas most HLA genetic associations are virus- or disease-specific, HLA-A*01 and HLA-A*02 allotypes may be more generally associated with immune susceptibility and control, respectively, across multiple herpesviruses. Connecting genetic association data with functional corroboration, we discuss mechanisms by which diverse HLA and cognate receptor allotypes direct variable immune responses during herpesvirus infection and pathogenesis. Together, this review examines the complexity of HLA-herpesvirus interactions driven by differential T cell and Natural Killer cell immune responses.

The immunogenetics of COVID-19 - Anshika Srivastava; Jill A. Hollenbach (Immunogenetics, 2023)

The immunogenetics of tuberculosis (TB) susceptibility - Carene Anne Alene Ndong Sima; Dayna Smith; Desiree C. Petersen; Haiko Schurz; Caitlin Uren; Marlo Möller (Immunogenetics, 2023)

Distinct frequency patterns of LILRB3 and LILRA6 allelic variants in Europeans - Arman A. Bashirova; Wojciech Kasprzak; Colm O’hUigin; Mary Carrington (Immunogenetics, 2023)
The leukocyte immunoglobulin–like receptor ( LILR ) B3 and LILRA6 genes encode homologous myeloid inhibitory and activating orphan receptors, respectively. Both genes exhibit a strikingly high level of polymorphism at the amino acid level and LILRA6 (but not LILRB3 ) displays copy number variation (CNV). Although multiple alleles have been reported for both genes, limited data is available on frequencies of these alleles among humans. We have sequenced LILRB3/A6 exons encoding signal peptides and ectodomains in 91 healthy blood donors of European descent who carry one or two copies of LILRA6 per diploid genome . Analysis of haplotypes among individuals with two LILRA6 copies, representing the majority in this cohort ( N = 86), shows that common LILRB3 and LILRA6 alleles encode some distinct amino acid sequences in homologous regions of the receptors, which could potentially impact their respective functions differentially. Comparison of sequences in individuals with one vs. two copies of LILRA6 supports non-allelic homologous recombination between LILRB3 and LILRA6 as a mechanism for generating LILRA6 CNV and LILRB3 diversity. These data characterize LILRB3/LILRA6 genetic variation in more detail than previously described and underscore the need to determine their ligands.

Genetic variation of glycophorins and infectious disease - Edward J. Hollox; Sandra Louzada (Immunogenetics, 2023)
Glycophorins are transmembrane proteins of red blood cells (RBCs), heavily glycosylated on their external-facing surface. In humans, there are four glycophorin proteins, glycophorins A, B, C and D. Glycophorins A and B are encoded by two similar genes GYPA and GYPB , and glycophorin C and glycophorin D are encoded by a single gene, GYPC . The exact function of glycophorins remains unclear. However, given their abundance on the surface of RBCs, it is likely that they serve as a substrate for glycosylation, giving the RBC a negatively charged, complex glycan “coat”. GYPB and GYPE (a closely related pseudogene) were generated from GYPA by two duplication events involving a 120-kb genomic segment between 10 and 15 million years ago. Non-allelic homologous recombination between these 120-kb repeats generates a variety of duplication alleles and deletion alleles, which have been systematically catalogued from genomic sequence data. One allele, called DUP4, encodes the Dantu NE blood type and is strongly protective against malaria as it alters the surface tension of the RBC membrane. Glycophorins interact with other infectious pathogens, including viruses, as well as the malarial parasite Plasmodium falciparum , but the role of glycophorin variation in mediating the effects of these pathogens remains underexplored.

Tumor necrosis factor-α induces proliferation and reduces apoptosis of colorectal cancer cells through STAT3 activation - Wei Wei; Juanhong Wang; Pu Huang; Siqi Gou; Daihua Yu; Lei Zong (Immunogenetics, 2023)

The + 3010/C single nucleotide polymorphism (rs1710) at the HLA-G 3′ untranslated region is associated with a short transcript exhibiting a deletion of 92 nucleotides - Erick C. Castelli; Gabriela Sato Paes; Isabelle Mira da Silva; Philippe Moreau; Eduardo A. Donadi (Immunogenetics, 2023)

Expression analysis of Carassius auratus-leukocyte-immune-type receptors (CaLITRs) during goldfish kidney macrophage development and in activated kidney leukocyte cultures - Jiahui Wang; Amro M. Soliman; Jeff Norlin; Daniel R. Barreda; James L. Stafford (Immunogenetics, 2023)

Correction to: Llama peripheral B-cell populations producing conventional and heavy chain-only IgG subtypes are phenotypically indistinguishable but immunogenetically distinct - Kevin A. Henry; Henk van Faassen; Doreen Harcus; Anne Marcil; Jennifer J. Hill; Serge Muyldermans; C. Roger MacKenzie (Immunogenetics, 2023)

Assessment of regulatory T cells (Tregs) and Foxp3 methylation level in chronic myeloid leukemia patients on tyrosine kinase inhibitor therapy - Shahla’a Fadhil Sabir; Bassam Francis Matti; Wifaq Mahmood Ali Alwatar (Immunogenetics, 2023)

Unfavorable immunotherapy plus tyrosine kinase inhibition outcome of metastatic renal cell carcinoma after radical nephrectomy with increased ADAM9 expression - Xianglai Xu; Ying Wang; Zhaoyi Chen; Yanjun Zhu; Jiajun Wang; Jianming Guo (Immunogenetics, 2023)

The antigen recognition portion of African buffalo class I MHC is highly polymorphic, consistent with a complex pathogen challenge environment, and the 3’ region suggests distinct haplotype configurations - Isaiah Obara; Ard Nijhof; Patrick Atimnedi; Domnic Mijele; Anne Nanteza; Khawla Elati; Richard Bishop (Immunogenetics, 2023)
African buffalo ( Syncerus caffer) have been distinct from the Auroch lineage leading to domestic cattle for 5 million years, and are reservoirs of multiple pathogens, that affect introduced domestic cattle. To date, there has been no analysis of the class I MHC locus in African buffalo. We present the first data on African buffalo class I MHC, which demonstrates that gene and predicted protein coding sequences are approximately 86–87% similar to that of African domestic cattle in the peptide binding region. The study also shows concordance in the distribution of codons with elevated posterior probabilities of positive selection in the buffalo class I MHC and known antigen binding sites in cattle. Overall, the diversity in buffalo class I sequences appears greater than that in cattle, perhaps related to a more complex pathogen challenge environment in Africa. However, application of NetMHCpan suggested broad clustering of peptide binding specificities between buffalo and cattle. Furthermore, in the case of at least 20 alleles, critical peptide-binding residues appear to be conserved with those of cattle, including at secondary anchor residues. Alleles with six different length transmembrane regions were detected. This preliminary analysis suggests that like cattle, but unlike most other mammals, African buffalo appears to exhibit configuration (haplotype) variation in which the loci are expressed in distinct combinations.

X-linked hyper-immunoglobulin M syndrome harboring a novel CD40-ligand gene mutation: a case report - Rahul Ramachandran; Yamini Krishnan; Parminder Singh; Ashok Kumar; Abhishek Mohanty (Immunogenetics, 2023)

Bioinformatics analysis of structural protein to approach a vaccine candidate against Vibrio cholerae infection - Elijah Kolawole Oladipo; Olawumi Elizabeth Akindiya; Glory Jesudara Oluwasanya; Gideon Mayowa Akanbi; Seun Elijah Olufemi; Daniel Adewole Adediran; Favour Oluwadara Bamigboye; Rasidat Oyindamola Aremu; Kehinde Temitope Kolapo; Jerry Ayobami Oluwasegun; Hezekiah Oluwajoba Awobiyi; Esther Moradeyo Jimah; et al. (Immunogenetics, 2023)

Age-dependent effect of the IFIH1/MDA5 gene variants on the risk of critical COVID-19 - María G. Muñiz-Banciella; Guillermo M. Albaiceta; Laura Amado-Rodríguez; Estefanía Salgado del Riego; Inés López Alonso; Cecilia López-Martínez; Paula Martín-Vicente; Marta García-Clemente; Tamara Hermida-Valverde; Ana I. Enríquez-Rodriguez; Cristina Hernández-González; Elías Cuesta-Llavona; et al. (Immunogenetics, 2023)

HLA-G expression in Merkel cell carcinoma and the correlation with Merkel cell polyomavirus infection - L. M. Parra; B. G. C. Sartori; D. R. Fernandes; L. R. V. Fachin; M. R. S. Nogueira; A. F. F. Belone; A. J. F. Nunes; F. C. Souza-Santana (Immunogenetics, 2023)

Whole exome sequencing identified a novel splice donor site variant in interleukin 2 receptor alpha chain - Nadia Waheed; Maryam Naseer; Nighat Haider; Sufyan Suleman; Asmat Ullah (Immunogenetics, 2023)

SNHG3 regulates NEIL3 via transcription factor E2F1 to mediate malignant proliferation of hepatocellular carcinoma - Fabiao Zhang; Jie Lu; Jian Yang; Qiqiang Dai; Xuefeng Du; Yongfu Xu; Caiming Zhang (Immunogenetics, 2023)

Mutated Pkhd1 alone is sufficient to cause autoimmune biliary disease on the nonobese diabetic (NOD) genetic background - David E. Adams; Luke S. Heuer; Manuel Rojas; Weici Zhang; William M. Ridgway (Immunogenetics, 2023)
We previously reported that nonobese diabetic (NOD) congenic mice (NOD. c3c4 mice) developed an autoimmune biliary disease (ABD) with similarities to human primary biliary cholangitis (PBC), including anti-mitochondrial antibodies and organ-specific biliary lymphocytic infiltrates. We narrowed the possible contributory regions in a novel NOD. Abd3 congenic mouse to a B10 congenic region on chromosome 1 (“ Abd3 ”) and a mutated Pkhd1 gene ( Pkhd1 del36−67 ) upstream from Abd3 , and we showed via backcrossing studies that the NOD genetic background was necessary for disease. Here, we show that NOD. Abd3 mice develop anti-PDC-E2 autoantibodies at high levels, and that placing the chromosome 1 interval onto a scid background eliminates disease, demonstrating the critical role of the adaptive immune system in pathogenesis. While the NOD genetic background is essential for disease, it was still unclear which of the two regions in the Abd3 locus were necessary and sufficient for disease. Here, using a classic recombinant breeding approach, we prove that the mutated Pkhd1 del36−67 alone, on the NOD background, causes ABD. Further characterization of the mutant sequence demonstrated that the Pkhd1 gene is disrupted by an ETnII-beta retrotransposon inserted in intron 35 in an anti-sense orientation. Homozygous Pkhd1 mutations significantly affect viability, with the offspring skewed away from a Mendelian distribution towards NOD Pkhd1 homozygous or heterozygous genotypes. Cell-specific abnormalities, on a susceptible genetic background, can therefore induce an organ-specific autoimmunity directed to the affected cells. Future work will aim to characterize how mutant Pkhd1 can cause such an autoimmune response.

IL4I1 enhances PD-L1 expression through JAK/STAT signaling pathway in lung adenocarcinoma - Jiefei Zhu; Yan Li; Xu Lv (Immunogenetics, 2023)

Functional consequences of allotypic polymorphisms in human immunoglobulin G subclasses - Andrew R. Crowley; Simone I. Richardson; Marina Tuyishime; Madeleine Jennewein; Meredith J. Bailey; Jiwon Lee; Galit Alter; Guido Ferrari; Lynn Morris; Margaret E. Ackerman (Immunogenetics, 2023)

A highly diverse set of novel immunoglobulin-like transcript (NILT) genes in zebrafish indicates a wide range of functions with complex relationships to mammalian receptors - Dustin J. Wcisel; Alex Dornburg; Sean C. McConnell; Kyle M. Hernandez; Jorge Andrade; Jill L. O. de Jong; Gary W. Litman; Jeffrey A. Yoder (Immunogenetics, 2023)

Oncogenic signaling pathway mediated by Notch pathway-related genes induces immunosuppression and immunotherapy resistance in hepatocellular carcinoma - Peng Ma; Chuanxin Zou; Shitao Xia (Immunogenetics, 2022)

Identification of potential predictive biomarkers and biological pathways and the correction with immune infiltration in the activation of Crohn’s disease - Wei-Ming Zhong; Xiao-Hang Qian; Zhe-Wu Jin (Immunogenetics, 2022)

Correction to: Multiple Alr genes exhibit allorecognition-associated variation in the colonial cnidarian Hydractinia - Henry Rodriguez-Valbuena; Andrea Gonzalez-Muñoz; Luis F. Cadavid (Immunogenetics, 2022)

Multiple Alr genes exhibit allorecognition-associated variation in the colonial cnidarian Hydractinia - Henry Rodriguez-Valbuena; Andrea Gonzalez-Muñoz; Luis F. Cadavid (Immunogenetics, 2022)

Natural LILRB1 D1-D2 variants show frequency differences in populations and bind to HLA class I with various avidities - Fuguo Liu; Alexander T. H. Cocker; Jason L. Pugh; Zakia Djaoud; Peter Parham; Lisbeth A. Guethlein (Immunogenetics, 2022)

Introducing our new Immunogenetics co-editor: Professor Andrew Brooks - Ronald E. Bontrop (Immunogenetics, 2022)

IgG subclasses in New World Monkeys: an issue for debate? - Jehymin D. Parra-Montaño; Kimberly C. Mateus-Rincon; Juliana V. Aranguren-Borrás; Mary Medrano-Robayo; Alejandro Figueredo-López; Laura M. González-Amaya; Juan D. Vega-Valderrama; Luisa F. González-Bautista; Andrea L. Becerra-Embus; Yury Aponte-Rubio; Heliairis Alfonso-González; Sindy P. Buitrago; et al. (Immunogenetics, 2022)

Fever as an evolutionary agent to select immune complexes interfaces - Vlad Tofan; Alina Lenghel; Maristela Martins de Camargo; Razvan Costin Stan (Immunogenetics, 2022)

TLR7 and TLR8 evolution in lagomorphs: different patterns in the different lineages - Fabiana Neves; João Pedro Marques; Helena Areal; Patrícia Pinto-Pinho; Bruno Colaço; José Melo-Ferreira; Margarida Fardilha; Joana Abrantes; Pedro José Esteves (Immunogenetics, 2022)

Identification of G-quadruplex DNA sequences in SARS-CoV2 - Amit K. Maiti (Immunogenetics, 2022)

iTTCA-MFF: identifying tumor T cell antigens based on multiple feature fusion - Hongliang Zou; Fan Yang; Zhijian Yin (Immunogenetics, 2022)

Sex differences in immune gene expression in the brain of a small shorebird - José O. Valdebenito; Kathryn H. Maher; Gergely Zachár; Qin Huang; Zhengwang Zhang; Larry J. Young; Tamás Székely; Pinjia Que; Yang Liu; Araxi O. Urrutia (Immunogenetics, 2022)
Males and females often exhibit differences in behaviour, life histories, and ecology, many of which are typically reflected in their brains. Neuronal protection and maintenance include complex processes led by the microglia, which also interacts with metabolites such as hormones or immune components. Despite increasing interest in sex-specific brain function in laboratory animals, the significance of sex-specific immune activation in the brain of wild animals along with the variables that could affect it is widely lacking. Here, we use the Kentish plover ( Charadrius alexandrinus ) to study sex differences in expression of immune genes in the brain of adult males and females, in two wild populations breeding in contrasting habitats: a coastal sea-level population and a high-altitude inland population in China. Our analysis yielded 379 genes associated with immune function. We show a significant male-biased immune gene upregulation. Immune gene expression in the brain did not differ in upregulation between the coastal and inland populations. We discuss the role of dosage compensation in our findings and their evolutionary significance mediated by sex-specific survival and neuronal deterioration. Similar expression profiles in the coastal and inland populations suggest comparable genetic control by the microglia and possible similarities in pathogen pressures between habitats. We call for further studies on gene expression of males and females in wild population to understand the implications of immune function for life-histories and demography in natural systems.

Individual copy number variation and extensive diversity between major MHC-DAB1 allelic lineages in the European bitterling - Lorenzo Talarico; Anna Bryjová; Dagmar Čížková; Karel Douda; Martin Reichard (Immunogenetics, 2022)
Polymorphism of the major histocompatibility complex (MHC), DAB1 gene was characterized for the first time in the European bitterling ( Rhodeus amarus ), a freshwater fish employed in studies of host-parasite coevolution and mate choice, taking advantage of newly designed primers coupled with high-throughput amplicon sequencing. Across 221 genotyped individuals, we detected 1–4 variants per fish, with 28% individuals possessing 3–4 variants. We identified 36 DAB1 variants, and they showed high sequence diversity mostly located within predicted antigen-binding sites, and both global and codon-specific excess of non-synonymous mutations. Despite deep divergence between two major allelic lineages, functional diversity was surprisingly low (3 supertypes). Overall, these findings suggest the role of positive and balancing selection in promotion and long-time maintenance of DAB1 polymorphism. Further investigations will clarify the role of pathogen-mediated selection to drive the evolution of DAB1 variation.

Correction to: Intra-specific copy number variation of MHC class II genes in the Siamese fighting fish - Anson Tsz Chun Wong; Derek Kong Lam; Emily Shui Kei Poon; David Tsz Chung Chan; Simon Yung Wa Sin (Immunogenetics, 2022)

Masanori Kasahara: Long-standing Immunogenetics co-editor steps down - Martin F. Flajnik (Immunogenetics, 2022)

COVID-19: impact on Public Health and hypothesis-driven investigations on genetic susceptibility and severity - Susana David; Guillermo Dorado; Elsa L. Duarte; Stephanie David-Bosne; João Trigueiro-Louro; Helena Rebelo-de-Andrade (Immunogenetics, 2022)

Dynamic evolution of Mhc haplotypes in cynomolgus macaques of different geographic origins - Natasja G. de Groot; Nanine de Groot; Annemiek J. M. de Vos-Rouweler; Annet Louwerse; Jesse Bruijnesteijn; Ronald E. Bontrop (Immunogenetics, 2022)

Habitat fragmentation in the Brazilian Atlantic Forest is associated with erosion of frog immunogenetic diversity and increased fungal infections - Anat M. Belasen; Kevin R. Amses; Rebecca A. Clemons; C. Guilherme Becker; L. Felipe Toledo; Timothy Y. James (Immunogenetics, 2022)

High-resolution human KIR genotyping - Jonathan Downing; Lloyd D’Orsogna (Immunogenetics, 2022)
Killer immunoglobulin-like receptors (KIR) regulate the function of natural killer cells through interactions with various ligands on the surface of cells, thereby determining whether natural killer (NK) cells are to be activated or inhibited from killing the cell being interrogated. The genes encoding these proteins display extensive variation through variable gene content, copy number and allele polymorphism. The combination of KIR genes and their ligands is implicated in various clinical settings including haematopoietic stem cell and solid organ transplant and infectious disease progression. The determination of KIR genes has been used as a factor in the selection of optimal stem cell donors with haplotype variations in recipient and donor giving differential clinical outcomes. Methods to determine KIR genes have primarily involved ascertaining the presence or absence of genes in an individual. With the more recent introduction of massively parallel clonal next-generation sequencing and single molecule very long read length third-generation sequencing, high-resolution determination of KIR alleles has become feasible. Determining the extent and functional impact of allele variation has the potential to lead to further optimisation of clinical outcomes as well as a deeper understanding of the functional properties of the receptors and their interactions with ligands. This review summarizes recently published high-resolution KIR genotyping methods and considers the various advantages and disadvantages of the approaches taken. In addition the application of allele level genotyping in the setting of transplantation and infectious disease control is discussed.

Myd88 knockdown with RNA interference induces in vitro immune hyporesponsiveness in dendritic cells from rhesus monkeys - Qiuhong Wang; Dongyun Cun; Desong Xu; Liang Lin; Jian Jiao; Li Zhang; Cheng Xi; Wei Li; Peng Chen; Mingdao Hu (Immunogenetics, 2022)

Comparative genetics of KIR haplotype diversity in humans and rhesus macaques: the balancing act - Jesse Bruijnesteijn; Nanine de Groot; Annemiek J. M. de Vos-Rouweler; Natasja G. de Groot; Ronald E. Bontrop (Immunogenetics, 2022)

Intra-specific copy number variation of MHC class II genes in the Siamese fighting fish - Anson Tsz Chun Wong; Derek Kong Lam; Emily Shui Kei Poon; David Tsz Chung Chan; Simon Yung Wa Sin (Immunogenetics, 2022)

The S100A7 nuclear interactors in autoimmune diseases: a coevolutionary study in mammals - Fabio D’Amico; Evangelia Skarmoutsou; Massimo Libra (Immunogenetics, 2022)

Defining the caprine γδ T cell WC1 multigenic array and evaluation of its expressed sequences and gene structure conservation among goat breeds and relative to cattle - Alehegne W. Yirsaw; Alexandra Gillespie; Fengqiu Zhang; Timothy P. L. Smith; Derek M. Bickhart; Karthick P. Gunasekaran; Maria Amir; Haeree Park; Janice C. Telfer; Cynthia L. Baldwin (Immunogenetics, 2022)

Prognostic implication and immunotherapy response prediction of a costimulatory molecule signature in kidney renal clear cell carcinoma - Gaoteng Lin; Yuanyuan Yang; Qingfu Feng; Fangfang Zhan; Chuangxin Sun; Yuanjie Niu; Gang Li (Immunogenetics, 2022)

Evaluation of telomeric KIR genes and their association with CMV infection in kidney transplant recipients - Negin Farzamikia; Seyyedeh Mina Hejazian; Mehdi Haghi; Seyyed Sina Hejazian; Sepideh Zununi Vahed; Mohammadreza Ardalan (Immunogenetics, 2022)

Immunoinformatics prediction of potential immunodominant epitopes from human coronaviruses and association with autoimmunity - Shilu Mathew; Aisha D. Fakhroo; Maria Smatti; Asmaa A. Al Thani; Hadi M. Yassine (Immunogenetics, 2022)

Combined overexpression of four transcription factors promotes effector T cell dedifferentiation toward early phenotypes - Lijun Yan; Yusheng Ou; Shengfang Xia; Jianqing Huang; Wenfeng Zhang; Hongwei Shao; Han Shen; Huaben Bo; Changli Tao; Jinquan Wang; Fenglin Wu (Immunogenetics, 2022)

Haplotype structures and polymorphisms of dog leukocyte antigen (DLA) class I loci shaped by intralocus and interlocus recombination events - Jiro Miyamae; Masaharu Okano; Kohei Nishiya; Fumihiko Katakura; Jerzy K. Kulski; Tadaaki Moritomo; Takashi Shiina (Immunogenetics, 2022)

Correction to: A survey of TIR domain sequence and structure divergence - Vladimir Y. Toshchakov; Andrew F. Neuwald (Immunogenetics, 2022)

NOD2 and reproduction-associated NOD-like receptors have been lost during the evolution of pangolins - Margarita Salova; Wolfgang Sipos; Erwin Tschachler; Leopold Eckhart (Immunogenetics, 2022)
NOD-like receptors (NLRs) are sensors of pathogen-associated molecular patterns with critical roles in the control of immune responses and programmed cell death. Recent studies have revealed inter-species differences in mammalian innate immune genes and a particular degeneration of nucleic acid sensing pathways in pangolins, which are currently investigated as potential hosts for zoonotic pathogens. Here, we used comparative genomics to determine which NLR genes are conserved or lost in pangolins and related mammals. We show that NOD2 , which is implicated in sensing bacterial muramyl dipeptide and viral RNA, is a pseudogene in pangolins, but not in any other mammalian species investigated. NLRC4 and NAIP are absent in pangolins and canine carnivorans, suggesting convergent loss of cytoplasmic sensing of bacterial flagellin in these taxa. Among NLR family pyrin domain containing proteins (NLRPs), skin barrier-related NLRP10 has been lost in pangolins after the evolutionary divergence from Carnivora. Strikingly, pangolins lack all NLRPs associated with reproduction (germ cells and embryonic development) in other mammals, i.e., NLRP2 , 4 , 5 , 7 , 8 , 9 , 11 , 13 , and 14 . Taken together, our study shows a massive degeneration of NLR genes in pangolins and suggests that these endangered mammals may have unique adaptations of innate immunity and reproductive cell biology.

Black fungus immunosuppressive epidemic with Covid-19 associated mucormycosis (zygomycosis): a clinical and diagnostic perspective from India - Kuljeet Singh; Sachin Kumar; Sourabh Shastri; Amrit Sudershan; Vibhakar Mansotra (Immunogenetics, 2022)

Sensing microbial infections in the Drosophila melanogaster genetic model organism - Samuel Liegeois; Dominique Ferrandon (Immunogenetics, 2022)

Evolution of RNA sensing receptors in birds - Katharine E. Magor (Immunogenetics, 2022)

Immunoglobulin-like receptors and the generation of innate immune memory - Mouhamad Al-Moussawy; Hossam A. Abdelsamed; Fadi G. Lakkis (Immunogenetics, 2022)

Secreted immunoglobulin domain effector molecules of invertebrates and management of gut microbial ecology - Assunta Liberti; Ojas Natarajan; Celine Grace F. Atkinson; Larry J. Dishaw (Immunogenetics, 2022)

Structural basis of NLR activation and innate immune signalling in plants - Natsumi Maruta; Hayden Burdett; Bryan Y. J. Lim; Xiahao Hu; Sneha Desa; Mohammad Kawsar Manik; Bostjan Kobe (Immunogenetics, 2022)
Animals and plants have NLRs (nucleotide-binding leucine-rich repeat receptors) that recognize the presence of pathogens and initiate innate immune responses. In plants, there are three types of NLRs distinguished by their N-terminal domain: the CC (coiled-coil) domain NLRs, the TIR (Toll/interleukin-1 receptor) domain NLRs and the RPW8 (resistance to powdery mildew 8)-like coiled-coil domain NLRs. CC-NLRs (CNLs) and TIR-NLRs (TNLs) generally act as sensors of effectors secreted by pathogens, while RPW8-NLRs (RNLs) signal downstream of many sensor NLRs and are called helper NLRs. Recent studies have revealed three dimensional structures of a CNL (ZAR1) including its inactive, intermediate and active oligomeric state, as well as TNLs (RPP1 and ROQ1) in their active oligomeric states. Furthermore, accumulating evidence suggests that members of the family of lipase-like EDS1 (enhanced disease susceptibility 1) proteins, which are uniquely found in seed plants, play a key role in providing a link between sensor NLRs and helper NLRs during innate immune responses. Here, we summarize the implications of the plant NLR structures that provide insights into distinct mechanisms of action by the different sensor NLRs and discuss plant NLR-mediated innate immune signalling pathways involving the EDS1 family proteins and RNLs.

On the relationship between extant innate immune receptors and the evolutionary origins of jawed vertebrate adaptive immunity - Alex Dornburg; Jeffrey A. Yoder (Immunogenetics, 2022)

The evolution of innate immune receptors: investigating the diversity, distribution, and phylogeny of immune recognition across eukaryotes - Katherine M. Buckley; Jeffrey A. Yoder (Immunogenetics, 2022)

Correction to: C. elegans: out on an evolutionary limb - Nathalie Pujol; Jonathan J. Ewbank (Immunogenetics, 2022)

Single-cell RNA-seq profiling of individual Biomphalaria glabrata immune cells with a focus on immunologically relevant transcripts - Hongyu Li; Abdullah A. Gharamah; Jacob R. Hambrook; Xinzhong Wu; Patrick C. Hanington (Immunogenetics, 2022)

Recurrent expansions of B30.2-associated immune receptor families in fish - Jaanus Suurväli; Colin J. Garroway; Pierre Boudinot (Immunogenetics, 2022)

The Hydractinia allorecognition system - Matthew L. Nicotra (Immunogenetics, 2022)

C. elegans: out on an evolutionary limb - Nathalie Pujol; Jonathan J. Ewbank (Immunogenetics, 2022)

Innate immune genes of the chicken MHC and related regions - Jim Kaufman (Immunogenetics, 2022)
Compared to the major histocompatibility complex (MHC) of typical mammals, the chicken BF/BL region is small and simple, with most of the genes playing central roles in the adaptive immune response. However, some genes of the chicken MHC are almost certainly involved in innate immunity, such as the complement component C4 and the lectin-like receptor/ligand gene pair BNK and Blec. The poorly expressed classical class I molecule BF1 is known to be recognised by natural killer (NK) cells and, analogous to mammalian immune responses, the classical class I molecules BF1 and BF2, the CD1 homologs and the butyrophilin homologs called BG may be recognised by adaptive immune lymphocytes with semi-invariant receptors in a so-called adaptate manner. Moreover, the TRIM and BG regions next to the chicken MHC, along with the genetically unlinked Y and olfactory/scavenger receptor regions on the same chromosome, have multigene families almost certainly involved in innate and adaptate responses. On this chicken microchromosome, the simplicity of the adaptive immune gene systems contrasts with the complexity of the gene systems potentially involved in innate immunity.

A reverse vaccinology and immunoinformatics approach for designing a multiepitope vaccine against SARS-CoV-2 - Ehsan Jahangirian; Ghadir A. Jamal; MohammadReza Nouroozi; Alemeh Mohammadpour (Immunogenetics, 2021)

A model integrating Killer Immunoglobulin-like Receptor (KIR) haplotypes for risk prediction of COVID-19 clinical disease severity - Meral Beksac; Hasan Yalim Akin; Emine Begum Gencer-Oncul; Mahsa Yousefzadeh; Guldane Cengiz Seval; Ezgi Gulten; Irem Akdemir Kalkan; Gule Cinar; Osman Memikoglu; Ergun Karaagaoglu; Klara Dalva (Immunogenetics, 2021)

Holosteans contextualize the role of the teleost genome duplication in promoting the rise of evolutionary novelties in the ray-finned fish innate immune system - Alex Dornburg; Dustin J. Wcisel; Katerina Zapfe; Emma Ferraro; Lindsay Roupe-Abrams; Andrew W. Thompson; Ingo Braasch; Tatsuya Ota; Jeffrey A. Yoder (Immunogenetics, 2021)

Bioinformatics-based study to identify immune infiltration and inflammatory-related hub genes as biomarkers for the treatment of rheumatoid arthritis - Sheng Fang; Xin Xu; Lin Zhong; An-quan Wang; Wei-lu Gao; Ming Lu; Zong-Sheng Yin (Immunogenetics, 2021)

Compound heterozygous DCLRE1C mutations lead to clinically typical Severe Combined Immunodeficiency presenting with Graft Versus Host Disease - Wenjun Mou; Liwei Gao; Jianxin He; Ju Yin; Baoping Xu; Jingang Gui (Immunogenetics, 2021)

Analyzing the characteristics of immune cell infiltration in lung adenocarcinoma via bioinformatics to predict the effect of immunotherapy - Yi Liao; Dingxiu He; Fuqiang Wen (Immunogenetics, 2021)

Computational identification and characterization of antigenic properties of Rv3899c of Mycobacterium tuberculosis and its interaction with human leukocyte antigen (HLA) - Ritam Das; Kandasamy Eniyan; Urmi Bajpai (Immunogenetics, 2021)

Polymorphism and varying selection within the MHC class I of four Anas species - Shidi Qin; Peter O. Dunn; Yang Yang; Hongyi Liu; Ke He (Immunogenetics, 2021)

High-resolution characterization of the structural features and genetic variation of six feline leukocyte antigen class I loci via single molecule, real-time (SMRT) sequencing - Jennifer C. Holmes; Elizabeth H. Scholl; Allison N. Dickey; Paul R. Hess (Immunogenetics, 2021)

Major histocompatibility complex genes and locus organization in the Komodo dragon (Varanus komodoensis) - Kent M. Reed; Robert E. Settlage (Immunogenetics, 2021)

The WC1 γδ T cell pathogen receptor of ruminants is preserved in the genome of ancient extinct auroch - Kathleen Loonie; Alexandria Gillespie; Cynthia Baldwin (Immunogenetics, 2021)

Plasma cell immunoglobulin heavy chain repertoire dynamics before and after tetanus booster vaccination - Kyle J. Wolf; Adebowale A. Adeyemo; Kim C. Williamson (Immunogenetics, 2021)

Evidence of genetic epistasis in autoimmune diabetes susceptibility revealed by mouse congenic sublines - Roxanne Collin; Véronique Dugas; Adam-Nicolas Pelletier; Geneviève Chabot-Roy; Sylvie Lesage (Immunogenetics, 2021)

HLA-DRB1 genes and the expression dynamics of HLA CIITA determine the susceptibility to T2DM - Rathika Chinniah; Vandit Sevak; Sasiharan Pandi; Padma Malini Ravi; Murali Vijayan; Arun Kannan; Balakrishnan Karuppiah (Immunogenetics, 2021)

Prediction of ATPase cation transporting 13A2 molecule in Petromyzon marinus and pan-cancer analysis into human tumors from an evolutionary perspective - Kaifeng Zheng; Tiesong Li (Immunogenetics, 2021)

Analysis of shark NCR3 family genes reveals primordial features of vertebrate NKp30 - Allison Kinlein; Morgan E. Janes; Jacob Kincer; Tereza Almeida; Hanover Matz; Jianxin Sui; Michael F. Criscitiello; Martin F. Flajnik; Yuko Ohta (Immunogenetics, 2021)

Correction to: Differences in pyroptosis of recent thymic emigrants CD4 + T Lymphocytes in ART‑treated HIV‑positive patients are influenced by sex - José Leandro Andrade‑Santos; Wlisses Henrique Veloso Carvalho‑Silva; Fabrício Oliveira Souto; Sergio Crovella; Rafael Lima Guimarães (Immunogenetics, 2021)

Differences in pyroptosis of recent thymic emigrants CD4+ T Lymphocytes in ART-treated HIV-positive patients are influenced by sex - José Leandro Andrade-Santos; Wlisses Henrique Veloso Carvalho-Silva; Fabrício Oliveira Souto; Sergio Crovella; Rafael Lima Guimarães (Immunogenetics, 2021)