International Journal of Immunogenetics最新文献

{"title":"Wildlife Trade and Genetic Basis of Disease Susceptibility: A Review","authors":"Oluwakayode Michael Coker,&nbsp;Olukunle Silas Fagbenro,&nbsp;Motunrayo Mojoyin Coker","doi":"10.1111/iji.70060","DOIUrl":"10.1111/iji.70060","url":null,"abstract":"<p>The surge in the trade of wildlife and wildlife products drives several species to extinction while coinciding with the increase in several zoonotic diseases. It is therefore essential to explore the roles of wildlife trade in disease transmission, and how the knowledge of genetics and immunogenetics can help in alleviating the attending challenges. Pathogen-driven selection plays a fundamental role in maintaining immune gene diversity, as individuals with alleles conferring resistance to endemic diseases have higher survival rate. However, anthropogenic disturbances, such as wildlife exploitation, can disrupt these evolutionary processes, leading to reduced genetic diversity and increased disease vulnerability. Advanced genomic tools, such as next-generation sequencing (NGS), whole-genome sequencing (WGS), CRISPR-Cas9 gene editing, genome-wide association studies (GWAS), epigenetics and transcriptomic analysis, can help identify immune gene variations and predict disease susceptibility in both wild and captive populations. Massive research targeting wildlife markets and the interface between the wild and the market players is necessary. It would be interesting to understand dynamics of pathogens and disease susceptibility, through the application of genetics and immunogenetics, thereby enhancing efforts to address the challenges posed by wildlife trade and zoonotic disease emergence.</p>","PeriodicalId":14003,"journal":{"name":"International Journal of Immunogenetics","volume":"53 5","pages":"353-361"},"PeriodicalIF":1.3,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/iji.70060","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148584305","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":"Antibodies to Non-HLA Antigens and Their Role in Organ Transplant Rejection","authors":"Katerina Jaklová,&nbsp;Katerina Vychytilová,&nbsp;Aneta Glosová,&nbsp;Antonij Slavcev","doi":"10.1111/iji.70063","DOIUrl":"10.1111/iji.70063","url":null,"abstract":"<p>Antibody-mediated rejection (AMR) is a serious post-transplant complication that is associated with a worse prognosis of survival of transplanted organs. The diagnosis of AMR is based on clinical, pathological characteristics and on the detection of antibodies specific to the organ donors’ mismatched human leukocyte antigens (HLA) antigens. Accumulating evidence in recent years however suggests that antibodies against antigens encoded by genes outside the HLA complex can play a role in the development of AMR. Non-HLA antigens are mostly expressed on the surface of endothelial and epithelial cells but can also be localized intracellularly and released in the bloodstream or lymph in case of cell lysis. Among these are major histocompatibility complex (MHC) Class I-related chain MICA, MICB, angiotensin II-R1 receptor (ATR1), collagen, K-α1 tubulin, cardiac myosin, vimentin and other molecules. Antibodies to non-HLA antigens can occur before transplantation but may be also produced de novo. The detection of non-HLA antibodies is carried out using the xMap (Luminex) technology, the so-called endothelial crossmatch and other techniques; however, these methodologies and interpretation of results have their pitfalls. In this short review, we briefly discuss the recent literature on the clinical role of non-HLA antibodies in organ transplant rejection and survival.</p>","PeriodicalId":14003,"journal":{"name":"International Journal of Immunogenetics","volume":"53 5","pages":"362-374"},"PeriodicalIF":1.3,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/iji.70063","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148792657","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":"Recommendations From the Implementation Steering Group for Organ Utilisation Histocompatibility and Immunogenetics Sub-Group: ISOU H&I Sub-Group Recommendations","authors":"Nicola C. Speirs,&nbsp;Victoria Chalker,&nbsp;Brendan Clark,&nbsp;Aisling E Courtney,&nbsp;Sunil Daga,&nbsp;Sian Griffin,&nbsp;Delordson Kallon,&nbsp;Jon Jin Kim,&nbsp;Vasilis Kosmoliaptsis,&nbsp;Katy Latham,&nbsp;Sarah Peacock,&nbsp;Olivia Shaw,&nbsp;Thomas Nieto,&nbsp;Rommel Ravanan,&nbsp;Richard Battle","doi":"10.1111/iji.70054","DOIUrl":"10.1111/iji.70054","url":null,"abstract":"<p>The Organ Utilisation Group was established to address barriers in solid organ transplantation and improve patient outcomes across the United Kingdom. The group produced a series of recommendations in February 2023. To address these recommendations, the Department of Health and Social Care formed the Implementation Steering Group for Organ Utilisation (ISOU). A dedicated Histocompatibility and Immunogenetics (H&amp;I) sub-group was formed with a remit to provide recommendations for HLA compatibility assessments and new technologies that could improve patient outcomes, within a 5 to 10 year time frame. The ISOU H&amp;I sub-group made five key recommendations, grouped under three themes: (1) implementation and digital capture of high-resolution HLA typing data for organ donor and recipients; (2) utilising high-resolution HLA typing data to improve donor/recipient compatibility assessment and patient outcomes and (3) use of other technologies/innovations to improve patient outcomes. This article discusses the recommendations with an emphasis on advanced technologies and methodologies such as high-resolution HLA typing, molecular matching, non-HLA antigen systems, donor-derived cell-free DNA (dd-cfDNA) and artificial intelligence (AI). Implementation of these recommendations aims to enhance organ matching, reduce immunological risk and improve equity and long-term outcomes for transplant recipients and position UK transplantation services at the forefront of innovation and patient-centred care.</p>","PeriodicalId":14003,"journal":{"name":"International Journal of Immunogenetics","volume":"53 4","pages":"324-331"},"PeriodicalIF":1.3,"publicationDate":"2026-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/iji.70054","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147941254","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 Variant rs2706682 at PITPNC1, Which Enhances Vehicular Secretion, Associated With Systemic Lupus Erythematosus Susceptibility in Chinese Populations","authors":"Ruiying Duan,&nbsp;Yuanyuan Qi,&nbsp;Yangming Zhang,&nbsp;Tengyu Zhu,&nbsp;Chen Liu,&nbsp;Huimiao Hu,&nbsp;Jia Guo,&nbsp;ZhanZheng Zhao,&nbsp;Dahai Yu","doi":"10.1111/iji.70056","DOIUrl":"10.1111/iji.70056","url":null,"abstract":"<div>\u0000 \u0000 <p>Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disease in which genetic and environmental factors play important role in SLE pathogenesis. Recently, cytoplasmic phosphatidylinositol transfer protein 1 (PITPNC1) was reported to be capable of enhancing vesicular secretion, which was correlated with autoimmune disorders contributing to SLE. Here, we aimed to explore the genetic association between <i>PITPNC1</i> polymorphisms and SLE susceptibility. The genetic association analysis included two cohorts: a discovery cohort (490 SLE cases vs. 493 healthy controls) and replication cohort (1003 SLE cases and 815 healthy controls). <i>rSNPBASE</i>, RegulomeDB databases, and Three-dimensional (3D) chromatin looping data were used for functional annotation, and luciferase reporter assay was performed for validation. The expression data from ArrayExpress were used for <i>PITPNC1</i> gene expression analysis. Three variants (rs4239092, p = 3.04×10⁻²; rs6504516, <i>p</i> = 3×10⁻²; rs2706682, <i>p</i> = 3.88×10⁻⁴) were significantly associated with the increased susceptibility to SLE in a previous GWAS cohort. The prominent rs2706682 was successfully replicated (<i>p</i> = 1.44×10⁻³), and the significance of genetic association was reinforced reaching 6.21×10⁻⁶ (OR 2.36, 95% CI 1.63–3.42). Functional analysis showed that rs2706682 is a regulatory SNP located within the strong transcription and enhancer chromatin state region. Further, dual-luciferase reporter gene assay demonstrated that the risk G allele correlated with increased expression. Finally, the gene expression analysis showed that the level of <i>PITPNC1</i> expression was significantly higher in patients with SLE. Our study identified that the variant rs2706682 in <i>PITPNC1</i>, encoding an important player in enhancing extracellular vesicles, was associated with SLE susceptibility.</p>\u0000 </div>","PeriodicalId":14003,"journal":{"name":"International Journal of Immunogenetics","volume":"53 4","pages":"344-350"},"PeriodicalIF":1.3,"publicationDate":"2026-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148015385","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":"Donor-Derived Cell-Free DNA Levels Predict Renal Allograft Biopsy Findings in a UK Single-Centre Study. Results of the KORAD Study","authors":"Patrick A. Flynn,&nbsp;Martin K. Rutter,&nbsp;Natalia Diaz Burlinson","doi":"10.1111/iji.70055","DOIUrl":"10.1111/iji.70055","url":null,"abstract":"<div>\u0000 \u0000 <p>Prior studies have shown that donor-derived cell-free DNA (dd-cfDNA) predicts renal biopsy-defined transplant rejection with a high negative predictive value (NPV). However, these studies were not in UK-based cohorts. The KORAD study aimed to assess relationships between dd-cfDNA levels and biopsy-defined rejection in a UK kidney transplant cohort, along with relationships with DSA and creatinine levels. dd-cfDNA was determined using AlloSeq cfDNA (CareDx) and DSA was identified with LABScreen single-antigen beads (Thermo Fisher Scientific). Eighty samples from 78 transplant patients had concomitant dd-cfDNA, DSA and creatinine results. The median percentage of dd-cfDNA in plasma samples with concomitant DSA negative results was significantly less than in DSA positive samples (0.37% vs. 3.15%, <i>p</i> = 0.002). There was no significant difference in the median percentage of dd-cfDNA in plasma samples with concomitant samples with elevated creatinine levels (0.41% vs. 0.36%, <i>p</i> = 0.779). Thirty-nine of these plasma samples had concomitant renal biopsy results. Thirty-two biopsies were negative for rejection and seven were positive for rejection. A receiver operating characteristic curve analysis showed that dd-cfDNA levels distinguished biopsy-defined rejection from no rejection with an acceptable AUC of 0.737 (95% CI, 0.485–0.987). The %dd-cfDNA threshold maximising overall correct classification was 0.7%. Using this threshold might have prevented 26 patients from undergoing renal biopsy unnecessarily, with two patients directed not to have a biopsy incorrectly (26 dd-cfDNA values being true negatives and two false negatives; NPV: 93% (95% CI, 83%–100%)), which outperformed the NPV for DSA: 88% (95% CI, 77%–99%) and creatinine 85% (95% CI, 69%–100%). We showed that the optimal dd-cfDNA threshold (0.7%) in this study was lower than the 1% threshold identified in non-UK studies. AlloSeq cfDNA (CareDx) with the optimal threshold showed an acceptable level of discrimination of biopsy-proven rejection and a potential to reduce the number of biopsies performed.</p>\u0000 </div>","PeriodicalId":14003,"journal":{"name":"International Journal of Immunogenetics","volume":"53 4","pages":"332-343"},"PeriodicalIF":1.3,"publicationDate":"2026-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148042249","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":"Introduction to Pharmacogenomics: Role of the Histocompatibility and Immunogenetics Laboratory in Personalised Medicine—Current Status and Future Prospects","authors":"William Martin Howell","doi":"10.1111/iji.70052","DOIUrl":"10.1111/iji.70052","url":null,"abstract":"<p>This review provides an introduction to the rapidly expanding field of pharmacogenomics and personalised medicine, with especial relevance and focus for those working in clinical Histocompatibility and Immunogenetics (H&amp;I) laboratories supporting HLA and disease immunogenetic testing and transplantation programmes. Drug efficacy and adverse drug reactions (ADRs) are defined, and the historical background to the field is introduced, along with a current overview of established clinically actionable gene–drug interactions. HLA associations with ADRs are reviewed, including those associations already tested for in many H&amp;I laboratories worldwide, along with a broader overview of published HLA and ADRs, to determine which—if any—associations are likely to be of clinical significance and might be added to the testing repertoire. This review is intended to inform such decision-making. In addition, pharmacogenomics as related to the transport and metabolism of immunosuppressive drugs used in clinical transplantation is considered, again with relevance to the testing repertoire of clinical H&amp;I laboratories. Finally, the expanding role of HLA genotyping in cancer immunotherapies is discussed, along with future developments in the broader pharmacogenomics field and how H&amp;I laboratories can contribute to this.</p>","PeriodicalId":14003,"journal":{"name":"International Journal of Immunogenetics","volume":"53 4","pages":"305-323"},"PeriodicalIF":1.3,"publicationDate":"2026-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/iji.70052","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147770995","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":"EXPRESSION OF CONCERN: Association of Polymorphisms in Interleukin-18 and Interleukin-28B With Hepatitis B Recurrence After Liver Transplantation in Chinese Han Population","authors":"","doi":"10.1111/iji.70057","DOIUrl":"10.1111/iji.70057","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;p&gt;&lt;b&gt;EXPRESSION OF CONCERN&lt;/b&gt;: Y. Li, Y. Shi, J. Chen, B. Cai, B. Ying, and L. Wang, “Association of Polymorphisms in Interleukin-18 and Interleukin-28B with Hepatitis B Recurrence after Liver Transplantation in Chinese Han Population,” &lt;i&gt;International Journal of Immunogenetics&lt;/i&gt; 39, no. 4 (2012): 346–352, https://doi.org/10.1111/j.1744-313X.2012.01097.x.&lt;/p&gt;\u0000 \u0000 &lt;p&gt;This Expression of Concern is for the above article, published online on 10 February 2012 in Wiley Online Library (wileyonlinelibrary.com), and has been issued by agreement between the journal Editor-in-Chief, Derek Middleton; and John Wiley &amp; Sons Ltd.&lt;/p&gt;\u0000 \u0000 &lt;p&gt;A third-party organization contacted the publisher regarding concerns pertaining to deceased donor organ sourcing practices in multiple articles, including this one. Credible reporting has been published widely which indicates that research featuring organ transplantation in China did not comply with international ethics standards. As reported by Rogers et al., organ donations in China were widely sourced from executed prisoners prior to 2010 (Rogers et al., 2019). China officially announced an end to the practice of harvesting organs from executed prisoners on 1 January 2015 (Dai and Xu, 2015). Prior to the official end of the practice, a voluntary organ donation program was piloted in select hospitals from 2010 to 2014 (Huang et al., 2013). The use of harvested organs from prisoners contravenes ethics guidelines that were in place at the time of publication, including guidelines from the Declaration of Helsinki and the Declaration of Istanbul.&lt;/p&gt;\u0000 \u0000 &lt;p&gt;The Materials and Methods section for this article indicates that relevant donors and patients who underwent liver transplantation at West China Hospital between April 2000 and March 2011 were included in the study. The article states that the study received approval from West China Hospital and that all participants provided informed consent. No information regarding organ donor sources was provided besides details about HBV positivity and donors’ genotypes and alleles. Although the Abstract and Materials and Methods both state that donors were enrolled in the study, the authors do not mention that there was any informed consent by donors. Because the majority of liver transplant cases reported in this article likely occurred before the existence of a voluntary organ donation program, serious doubts remain regarding the origins of these donations and the ability of donors to have provided free and willing informed consent in order to participate in this study.&lt;/p&gt;\u0000 \u0000 &lt;p&gt;The authors did not respond to inquiries made by the publisher. As such, the publisher and editors are not able to verify the institutional review board or ethics committee registration, or the informed consent protocols, for the study. Furthermore, quest","PeriodicalId":14003,"journal":{"name":"International Journal of Immunogenetics","volume":"53 4","pages":""},"PeriodicalIF":1.3,"publicationDate":"2026-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/iji.70057","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148264433","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":"Long-Read Next-Generation Sequencing Technologies Can Address Some Limitations of Short-Read Technologies in HLA Typing.","authors":"Julien Lion, Marianne Perriere, Judith Desoutter, Nicolas Guillaume","doi":"10.1111/iji.70046","DOIUrl":"10.1111/iji.70046","url":null,"abstract":"<p><strong>Introduction: </strong>Accurate HLA allele identification is essential to ensure graft-recipient compatibility. Advances in next-generation sequencing (NGS), such as those provided by Illumina and Oxford Nanopore Technologies, have improved resolution of HLA-typing.</p><p><strong>Methods and results: </strong>Here, a novel HLA-C*12 allele with a silent mutation (G to A) was identified in a bone marrow donor homozygous for HLA-C*12. The allele was initially linked to HLA-C*12:03:01 by short-read NGS, but further investigation by long-read sequencing revealed the mutation to be associated with HLA-C*12:02:02. Phasing limitations of short-read NGS made accurate allele assignment difficult, but precise differentiation became possible with longer reads. The origin of the mutation was subsequently confirmed by sequencing parental samples.</p><p><strong>Conclusion: </strong>This case highlights the ability of long-read sequencing to resolve cis-trans ambiguities and improve allele phasing, and to enhance accuracy for new HLA allele identification.</p>","PeriodicalId":14003,"journal":{"name":"International Journal of Immunogenetics","volume":" ","pages":"298-301"},"PeriodicalIF":1.3,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147457008","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 Simplified, Scalable Solution for Simultaneous Genotyping of Human Leukocyte Antigen Classical Class I and Human Platelet Antigen Genes Utilising Oxford Nanopore Technologies Long-Read Sequencing.","authors":"Vrushank Makwana, Rohan Raval, Clare Nevin, Ruifeng Zhang, William Martin Howell, Tom Browne","doi":"10.1111/iji.70049","DOIUrl":"10.1111/iji.70049","url":null,"abstract":"<p><p>Human leucocyte antigen (HLA) class I and human platelet antigens (HPAs) can elicit immune responses, leading to platelet transfusion refractoriness (PTRs). To support the clinical management of patients with PTR, transfusion of HLA class I and sometimes HPA-selected apheresis platelets is recommended. To facilitate this service, the HLA class I and HPA genotypes of platelet donors must be defined so that appropriate platelet units may be selected. Currently, National Health Service Blood and Transplant (NHSBT) utilises two separate assays for genotyping HLA class I and HPAs. In this study, a simple, single-well, multiplex PCR assay has been developed to genotype classical HLA class I genes (HLA-A, -B and -C) and 27/35 currently described HPAs, including all clinically relevant HPAs. Genomic DNA from 90 consented English apheresis platelet donors and 17 reference samples provided by the Australian Red Cross were amplified with the custom PCR protocol. Sequencing libraries were prepared using Oxford Nanopore Technologies (ONTs) native barcoding kit v14 (SQK-NBD114.96) and sequenced on MinION R10.4.1 flow cell. Base calling was performed live in MinKNOW v24.02.16, and sequence alignment, variant calling and genotype assignment of HPA were performed by a bespoke bioinformatics pipeline. Analysis of HLA class I genes was carried out using NGSengine v4.0.0. English apheresis platelet donors successfully genotyped (89/90) using the described assay showed 100% concordance with historic results for both HLA and clinically relevant HPAs. Further testing with reference samples from the Australian Red Cross samples showed 100% concordance with externally provided HPA results. This assay offers a simplified workflow for simultaneous HLA class I and HPA genotyping of apheresis platelet donors, permitting automation and significant expansion to include more HPA specificities. This assay provides accurate HLA class I genotyping and HPA genotyping in a single assay, requiring a minimal laboratory footprint and less maintenance than current in-use assays.</p>","PeriodicalId":14003,"journal":{"name":"International Journal of Immunogenetics","volume":" ","pages":"275-283"},"PeriodicalIF":1.3,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147622964","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":"Identification of HLA-DQA1 and HLA-DRB5 as Risk Factors for Multiple Sclerosis: An Epigenome-Wide Methylation Haplotype Association Analysis.","authors":"Zhenwei Shang, Jiacheng Wang, Jing Xu, Mingming Zhang, Hongchao Lv, Yongshuai Jiang, Ruijie Zhang, Wenhua Lv","doi":"10.1111/iji.70043","DOIUrl":"10.1111/iji.70043","url":null,"abstract":"<p><p>Multiple sclerosis (MS) is a chronic central nervous system inflammatory disease of autoimmune aetiology. The disease is mostly considered due to a complex interaction between different genetic and environmental factors. DNA methylation is an epigenetic mechanism that can influence gene expression and has the potential to mediate the effects of environmental factors on MS. This study aimed to identify MS risk methylation haplotypes (meplotypes) and their associated genes by integrating epigenome-wide meplotype association analysis with gene optimisation. We conducted the first epigenome-wide meplotype association study for MS using methylation data from peripheral blood lymphocytes (PBLs) of 140 MS patients and 139 normal controls. The analytical procedure comprised the following steps: (1) conversion of DNA methylation level into menotypes; (2) identification of methylation disequilibrium (MD) block and performance of meplotype association analysis; (3) screening of risk meplotypes and their mapping to genes; (4) conducting functional analysis of the candidate genes; and (5) final identification of MS risk genes through gene optimisation. Our analysis identified 286 meplotypes across 191 MD blocks that were significantly associated with MS (p value < 0.05). Of these, 120 meplotypes were found to confer increased risk for MS susceptibility and were mapped to 134 candidate genes. Gene optimisation identified four MS risk meplotypes on three key genes: HLA-DQA1, HLA-DRB5 and HLA-DRB1. These results not only confirm the pivotal role of HLA-DRB1 in MS but also report, for the first time, an association between MS and DNA methylation patterns in HLA-DQA1 and HLA-DRB5. This study demonstrates that epigenome-wide methylation haplotype analysis offers a powerful and novel perspective for identifying MS-related genes.</p>","PeriodicalId":14003,"journal":{"name":"International Journal of Immunogenetics","volume":" ","pages":"248-258"},"PeriodicalIF":1.3,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147270962","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}