Immunogenetics最新文献

{"title":"Using bioinformatics to investigate functional diversity: a case study of MHC diversity in koalas.","authors":"Luke W Silver, Elspeth A McLennan, Julian Beaman, Karen Burke da Silva, Peter Timms, Carolyn J Hogg, Katherine Belov","doi":"10.1007/s00251-024-01356-6","DOIUrl":"10.1007/s00251-024-01356-6","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":13446,"journal":{"name":"Immunogenetics","volume":" ","pages":"381-395"},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11496358/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142377863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"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.","authors":"Sudan Tao, Xuan You, Nanying Chen, Lina Dong, Shuoxian Zhao, Yizhen He, Wei Zhang, Faming Zhu","doi":"10.1007/s00251-024-01349-5","DOIUrl":"10.1007/s00251-024-01349-5","url":null,"abstract":"<p><p>The Zhejiang Han population, a subgroup of the Southern Han ethnic group, resides in Zhejiang Province, situated on the southeast coast of China. In this study, we conducted HLA genotyping for 813 voluntary umbilical cord blood donors from the Zhejiang Han population, targeting 11 HLA loci, namely HLA-A, HLA-B, HLA-C, HLA-DRB1, HLA-DRB3/4/5, HLA-DQA1, HLA-DQB1, HLA-DPA1, and HLA-DPB1, using the next-generation sequencing method. Our analysis of the alleles and haplotypes revealed a high degree of polymorphism within these loci. A total of 289 unique HLA alleles were identified, with the HLA-B locus exhibiting the most significant diversity, while HLA-DRB4 displayed the lowest variation. Due to the inherent limitations of the sequencing method, some unresolvable alleles in the specific loci, such as HLA-DRB1, HLA-DPA1, and HLA-DPB1, were assigned as G group designation. In our comprehensive analysis across all 11 HLA loci, a total of 1204 haplotypes were estimated. The distribution of these alleles was similar to those of the Chinese Southern Han population while highly different from the Caucasian population. These findings contribute to a deeper understanding of the genetic characteristics of HLA loci within the Chinese Southern Han population.</p>","PeriodicalId":13446,"journal":{"name":"Immunogenetics","volume":" ","pages":"305-314"},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141897349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spatial variation in toll-like receptor diversity in koala populations across their geographic distribution.","authors":"Jian Cui, Kimberley C Batley, Luke W Silver, Elspeth A McLennan, Carolyn J Hogg, Katherine Belov","doi":"10.1007/s00251-024-01365-5","DOIUrl":"https://doi.org/10.1007/s00251-024-01365-5","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":13446,"journal":{"name":"Immunogenetics","volume":"77 1","pages":"5"},"PeriodicalIF":2.9,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11608166/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142768596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of Complement Factor H gene polymorphisms and their association with clinical manifestations ofleptospirosis.","authors":"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","doi":"10.1007/s00251-024-01362-8","DOIUrl":"https://doi.org/10.1007/s00251-024-01362-8","url":null,"abstract":"<p><p>Leptospirosis is caused by pathogenic leptospires, posing a significant public health problem. Host susceptibility to Leptospira infection is a multifactorial trait, and the host's genetic background can influence both the establishment of infection and the severity of the disease. Complement Factor H (FH) plays a crucial role in the interaction between pathogenic bacteria and the host. Genetic variants in the FH gene CFH have previously been associated with non-infectious diseases. Here, we aimed to analyze the effect of CFH variants on individual susceptibility to leptospirosis and disease severity. To accomplish this, we sequenced CFH exons 7, 9, 21, 22, and 23 in a case/control cohort (184/162) from two endemic leptospirosis areas in Brazil and Argentina. We identified twenty-one single nucleotide variants (SNVs). In the Brazilian cohort, the intronic variant rs34815383 exhibited a higher frequency in patients than in controls, resulting in a significant association with leptospirosis (p = 0.032; OR: 0.32; 95% CI 0.1-1) and also renal disorder (p = 0.001; OR: 5.3; 95%CI 1.8-15.57). This SNV is reported to be a splicing variant, negatively impacting CFH expression, and has previously been associated with Complement-driven renal disease. A second synonymous variant, rs61822181, was significantly less frequent in patients than in controls (p = 0.002; OR: 7.33; 95% CI 1.59-33.7), representing a protective factor against the development of leptospirosis. Our study represents the first documentation of the frequency of CFH SNVs in South America and identifies the variant rs34815383 T > C as a risk factor for leptospirosis and leptospirosis-related renal complications.</p>","PeriodicalId":13446,"journal":{"name":"Immunogenetics","volume":"77 1","pages":"4"},"PeriodicalIF":2.9,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142768594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the therapeutic potential of interleukin-6 receptor blockade in autoimmune diseases using drug target mendelian randomization.","authors":"Jiaxin Li, Yalin Liu, Zheng Xiao, Chenyang Zang, Peihong Li, Bo Xiao, Luo Zhou","doi":"10.1007/s00251-024-01360-w","DOIUrl":"https://doi.org/10.1007/s00251-024-01360-w","url":null,"abstract":"<p><p>The blockade of the interleukin 6 receptor (IL-6R) demonstrates significant potential in various autoimmune diseases (ADs); however, the underlying therapeutic efficacy associated with this approach remains elusive. We conducted a comprehensive Mendelian randomization (MR) analysis based on large-scale genome-wide association studies to investigate the causal relationships between genetically proxied IL-6R blockade weighted by serum C-reactive protein levels and eighteen common ADs. Rheumatoid arthritis, COVID-19 infection, and COVID-19 critical illness were utilized as positive controls. The inverse-variance weighted (IVW) method was utilized as the primary analytical tool, while genetic colocalization analysis was conducted to further substantiate the causalities. Genetically proxied IL-6R blockade exhibited causally protective effects on all positive control diseases. After Bonferroni correction to IVW estimates, genetically proxied IL-6R blockade may significantly increase the risk of asthma (OR=1.031, P=2.15×10^-12) and eczema (OR=1.066, P=5.92×10^-22), while reducing the risk of ankylosing spondylitis (OR=0.341, P=1.39×10^-5), Crohn's disease (OR=0.556, P=2.21×10^-3), and type 1 diabetes (OR=0.410, P=1.78×10^-7). Additionally, genetically proxied IL-6R blockade would suggestively reduce the risk of multiple sclerosis (OR=0.713, P=1.13×10^-2). The results were robust under sensitivity analysis. For genetic colocalization analysis, we identified a shared causal variant rs531479718 linking serum C-reactive protein levels and asthma (posterior probability H4=0.998). Overall, our MR study demonstrated that genetically proxied IL-6R blockade may be causally associated with an increased risk of asthma and eczema, while concurrently diminishing the risk of ankylosing spondylitis, Crohn's disease, type 1 diabetes, and multiple sclerosis. These findings carry substantial implications for informing the therapeutic utilization of IL-6R blockade in the management of ADs.</p>","PeriodicalId":13446,"journal":{"name":"Immunogenetics","volume":"77 1","pages":"3"},"PeriodicalIF":2.9,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142716283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel mutation in FNIP1 associated with a syndromic immunodeficiency and cardiomyopathy.","authors":"Ilia Spivak, Atar Lev, Amos J Simon, Ortal Barel, Ido Somekh, Raz Somech","doi":"10.1007/s00251-024-01359-3","DOIUrl":"10.1007/s00251-024-01359-3","url":null,"abstract":"<p><p>Genetic variants in Folliculin interacting 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).</p>","PeriodicalId":13446,"journal":{"name":"Immunogenetics","volume":"77 1","pages":"2"},"PeriodicalIF":2.9,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11561061/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142619357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epistatic effects of IGHG and FCGRIIB genes on the development of Alzheimer's disease in African Americans.","authors":"Janardan P Pandey, Paul J Nietert, Aryan M Namboodiri, David A Bennett, Lisa L Barnes","doi":"10.1007/s00251-024-01358-4","DOIUrl":"10.1007/s00251-024-01358-4","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":13446,"journal":{"name":"Immunogenetics","volume":"77 1","pages":"1"},"PeriodicalIF":2.9,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11532319/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A genome assembly and transcriptome atlas of the inbred Babraham pig to illuminate porcine immunogenetic variation","authors":"John C. Schwartz, Colin P. Farrell, Graham Freimanis, Andrew K. Sewell, John D. Phillips, John A. Hammond","doi":"10.1007/s00251-024-01355-7","DOIUrl":"https://doi.org/10.1007/s00251-024-01355-7","url":null,"abstract":"<p>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.</p>","PeriodicalId":13446,"journal":{"name":"Immunogenetics","volume":"117 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142261410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sequence variants underlying severe combined immunodeficiency and leukocyte adhesion deficiency type 1 in six consanguineous families","authors":"Hajra Fayyaz, Atteaya Zaman, Nighat Haider, Rehmana Waris, Muhammad Hussain, Syed Irfan Raza, Wasim Ahmad, Imran Ullah","doi":"10.1007/s00251-024-01353-9","DOIUrl":"https://doi.org/10.1007/s00251-024-01353-9","url":null,"abstract":"<p>Inborn errors of immunity (IEI) are defined as genetic disorders affecting the immune system and resulting in diverse clinical signs and symptoms. Despite the lack of diagnosis and unavailability of IEI estimation in the Pakistani population, consanguinity is exacerbating its prevalence. The current study focuses on severe combined immunodeficiency (SCID) and leukocyte adhesion deficiency type 1 (LAD1). SCID is associated with the life-threatening symptoms developing at post-birth. LAD1 is clinically characterized by recurrent bacterial infections related to the skin, mouth, and respiratory tract owing to impaired leukocytes. Herein, in six consanguineous families, flow cytometry was used to evaluate the patient’s immune status. Whole-exome sequencing (WES) was then conducted to search for the causative variations in immunodeficiency genes. Sanger sequencing was used to assess the segregation of the variants with the disorder within the families. Sequence analysis revealed five homozygous variants in four different causative genes. This included four novel nonsense variants in <i>CD70</i> p.(Thr126Profs*33), <i>CD3e</i> p.(Trp151*), <i>IL7R</i> p.(Val138Ilefs*10), and <i>ITGB2</i> p.(Ser627Valfs*61), and one previously reported in <i>ITGB2</i> p.(Cys62*). In one of the families, two variants in two different genes, including <i>DNAH6</i> p.(Tyr2653His) and <i>NIPAL4</i> p.(Gly121Ser), were detected in an unclassified patient. All the identified variants were found in a homozygous state in the patient but in a heterozygous state in the available parents. The study will facilitate the diagnosis and management of IEI patients.</p>","PeriodicalId":13446,"journal":{"name":"Immunogenetics","volume":"211 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142261443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"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","authors":"Ata Shirizadeh, Zahra Razavi, Vahid Saeedi, Mahdi Behzad, Javad Faradmal, Ghasem Solgi","doi":"10.1007/s00251-024-01354-8","DOIUrl":"https://doi.org/10.1007/s00251-024-01354-8","url":null,"abstract":"<p>This study aimed to investigate the prevalence of insulin autoantibody (IAA), glutamic acid decarboxylase antibody (GADA), and insulinoma-associated antigen-2 antibody (IA-2A) in type 1 diabetes (T1D) children based on the presence of predisposing <i>HLA-II</i> alleles. Additionally, to assess the sequence homology between autoantigens of islet cells and selected proteins derived from gut bacteria in terms of their binding capacities to <i>HLA</i> risk alleles, <i>HLA-DRB1/DQB1</i> alleles were determined by PCR-SSOP in 111 T1D children (probands) along with 222 parents and 133 siblings. Autoantibodies were measured by ELISA, and in silico analysis was run as follows: protein extraction, homology and epitope prediction, peptide alignment, and HLA-peptide docking. Higher significant frequencies of <i>DRB1*03:01</i>, <i>DQB1*02:01</i>, and <i>DQB1*03:02</i> alleles and <i>DRB1*03:01</i> ~ <i>DQB1*02:01</i> haplotype and lower frequencies of <i>DRB1*11:01</i>, <i>DRB1*14:01</i>, and <i>DQB1*03:01</i> alleles were found in probands compared to parents and siblings. <i>DRB1*11:01</i> ~ <i>DQB1*03:01</i>, <i>DRB1*14:01</i> ~ <i>DQB1*05:03</i>, and <i>DRB1*15:01-DQB1*06:02</i> haplotypes were significantly less frequent in the probands compared to parents. Out of 111 probands, 21 were seronegative, 90 tested positive for one autoantibody, and 15 showed the concurrent presence of three autoantibodies. Logistic regression analysis revealed that <i>DRB1*04</i> ~ <i>DQB1*03:02</i> haplotype was associated with the induction of GADA and IA-2A, while <i>DRB1*11:01</i> ~ <i>DQB1*03:01</i> was associated with seronegativity. Epitopes derived from GAD and gut bacteria showed strong binding capacities to <i>HLA</i> risk alleles. Due to the sequence similarities between gut bacteria-derived proteins and islet cell autoantigens and their potential for binding to <i>HLA</i> risk alleles, dysbiosis of gut microbiota can be considered another risk factor for the development of T1D, especially in genetically susceptible individuals.</p>","PeriodicalId":13446,"journal":{"name":"Immunogenetics","volume":"9 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142261444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}