HLA最新文献

{"title":"Identification of Candidate Immunodominant Epitopes and Their HLA-Binding Prediction on BK Polyomavirus Proteins in Healthy Donors","authors":"Ana Gabriela Lara-de-León,&nbsp;Rut Mora-Buch,&nbsp;Ester Cantó,&nbsp;Cleofé Peña-Gómez,&nbsp;Francesc Rudilla","doi":"10.1111/tan.15722","DOIUrl":"10.1111/tan.15722","url":null,"abstract":"<div>\u0000 \u0000 <p>BK polyomavirus infection is an important cause of graft loss in transplant patients, however, currently available therapies lack effectiveness against this pathogen. Identification of immunological targets for potential treatments is therefore necessary. The aim of this study was to predict candidates of immunodominant epitopes within four BK virus proteins (VP1, VP2, VP3 and LTA) using PBMCs from 44 healthy donors. We used the ELISpot epitope mapping method to evaluate the T-cell response, and HLA-peptide binding was predicted using the NetMHCpan algorithm. A total of 11 potential peptides were selected for VP1, 3 for VP2/VP3 and 13 for LTA. Greater reactivity was observed for VP1 and LTA proteins compared with VP2/VP3. Most of the peptides selected as potential immunodominant candidates were restricted towards several HLA class I and II alleles, with predominant HLA class I binding by computational predictions. Based on these findings, the sequences of the selected immunodominant epitopes candidates and their corresponding HLA restrictions could contribute to the optimisation of functional assays and aid in the design and improvement of immunotherapy strategies against BK virus infections.</p>\u0000 </div>","PeriodicalId":13172,"journal":{"name":"HLA","volume":"104 4","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142464144","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":"Peptide Sharing Between CMV and Mismatched HLA Class I Peptides Promotes Early T-Cell-Mediated Rejection After Kidney Transplantation","authors":"Emma T. M. Peereboom,&nbsp;Renato de Marco,&nbsp;Kirsten Geneugelijk,&nbsp;Jasvir Jairam,&nbsp;Frans M. Verduyn Lunel,&nbsp;Anna J. Blok,&nbsp;José Medina-Pestana,&nbsp;Maria Gerbase-DeLima,&nbsp;Arjan D. van Zuilen,&nbsp;Eric Spierings","doi":"10.1111/tan.15719","DOIUrl":"10.1111/tan.15719","url":null,"abstract":"<p>Cytomegalovirus (CMV) infection is related to acute rejection and graft loss after kidney transplantation, though the underlying mechanism remains largely unknown. Some CMV strains produce a peptide that is identical to a peptide sequence found in the leader peptide of specific HLA-A and -C alleles. In this retrospective study of 351 kidney transplantations, we explored whether CMV-seropositive recipients without the VMAPRTLIL, VMAPRTLLL or VMAPRTLVL HLA class I leader peptide receiving a transplant from a donor with this peptide, faced an increased risk of T-cell-mediated rejection (TCMR) in the first 90 days after transplantation. An independent case–control cohort was used for validation (<i>n</i> = 122). The combination of recipient CMV seropositivity with the VMAPRTLIL peptide mismatch was associated with TCMR with a hazard ratio (HR) of 3.06 (<i>p</i> = 0.001) in a multivariable analysis. Similarly, the VMAPRTLLL peptide mismatch was associated with TCMR revealing a HR of 2.61 (<i>p</i> = 0.008). Transplantations featuring either a VMAPRTLIL or a VMAPRTLLL peptide mismatch had a significantly higher cumulative TCMR incidence (<i>p</i> &lt; 0.0001), with the primary impact observed in the first 2 weeks post-transplantation. The findings could be validated in an independent cohort. Together, our data strongly suggest that CMV-positive recipients without an HLA peptide identical to a CMV peptide yet transplanted with a donor who does possess this peptide, have a significantly increased risk of early TCMR. Considering the prevention of such an leader peptide mismatch in these patients or adjusting immunosuppression protocols accordingly may hold promise in reducing the incidence of early TCMR.</p>","PeriodicalId":13172,"journal":{"name":"HLA","volume":"104 4","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/tan.15719","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142464148","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":"Revolutionising High Resolution HLA Genotyping for Transplant Assessment: Validation, Implementation and Challenges of Oxford Nanopore Technologies' Q20+ Sequencing","authors":"Naser El-Lagta,&nbsp;Linh Truong,&nbsp;Felipe Ayora,&nbsp;Fredrick Mobegi,&nbsp;Samuel Bruce,&nbsp;Patricia Martinez,&nbsp;Lloyd D'Orsogna,&nbsp;Dianne De Santis","doi":"10.1111/tan.15725","DOIUrl":"10.1111/tan.15725","url":null,"abstract":"<p>The advent of third-generation sequencing (TGS) represents a significant shift in the field of genetic sequencing, enabling single-molecule sequencing to overcome limitations of short-read NGS platforms. Several studies have assessed the utilisation of TGS in HLA genotyping, though many of these studies have described the high error rate as an obstacle to achieving a robust and highly accurate HLA typing assay. In 2021, Oxford Nanopore Technologies (ONT) released the high-accuracy sequencing Kit 14 and the MinION flow cell model R10.4.1, which were reported to achieve sequencing accuracies up to 99%. The aim of this study was to validate this novel high-accuracy sequencing kit for HLA genotyping coupled with a full-gene HLA PCR assay. Comparison with historical data obtained using legacy flow cell models such as R9.4, R10.3 and R10.4 was also done to assess progressive improvement in sequencing performance with each sequential release. The workflow was validated based on data throughput, sequence quality and accuracy, and HLA genotyping resolution. An initial validation was performed using an internal reference panel of 42 samples representing common HLA allele groups, followed by an analysis of data obtained from 111 sequencing batch runs since the implementation, to assess assay performance and define quality control metrics to assess inter-run variability and monitor quality. Furthermore, challenges arising from MinION flow cell stability and use, and assessment of barcode contamination are discussed. The findings of this study highlight advantages of ONT sequencing kit 14/R10.4.1 for HLA genotyping and the implementation considerations for the routine diagnostic HLA laboratory.</p>","PeriodicalId":13172,"journal":{"name":"HLA","volume":"104 4","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/tan.15725","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142464150","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":"Foetal Microchimerism Correlates With Foetal-Maternal Histocompatibility Both During Pregnancy and Postpartum","authors":"Anne Cathrine Staff,&nbsp;Heidi E. Fjeldstad,&nbsp;Maria B. Olsen,&nbsp;Jonas Øgaard,&nbsp;Marte K. Viken,&nbsp;Cynthia S. M. Kramer,&nbsp;Michael Eikmans,&nbsp;Thomas Kroneis,&nbsp;Katja Sallinger,&nbsp;Sami B. Kanaan,&nbsp;Meryam Sugulle,&nbsp;Daniel P. Jacobsen","doi":"10.1111/tan.15717","DOIUrl":"10.1111/tan.15717","url":null,"abstract":"<p>Foetal cells are detectable in women decades postpartum, a state termed foetal microchimerism. The interplay between these semi-allogeneic foetal cells and the mother could be affected by genetic mismatches in the HLA loci. Here, we relate HLA allele and molecular mismatch values to the presence and quantity of foetal microchimerism in the maternal circulation during pregnancy and postpartum. A total of 76 pregnant women were included, of which 59 were followed up 1–8 years postpartum. Maternal and foetal DNA was genotyped for HLA class I and II loci. Foetal cells in maternal buffy coat were detected by qPCR, targeting inherited paternal alleles. Antibody-verified eplet mismatch and Predicted Indirectly Recognisable HLA Epitopes (PIRCHE) scores were calculated to quantify foetal-maternal histocompatibility from the mother's perspective. Circulating foetal cells were detected in 50.0% (38/76) of women during pregnancy, and 25.4% (15/59) postpartum. During pregnancy, HLA class II antibody-verified eplet mismatch load and PIRCHE scores correlated negatively with the presence and quantity of foetal cells in the maternal circulation. Postpartum, HLA class I allele mismatches correlated negatively with foetal microchimerism presence, while HLA class II allele mismatches, HLA class I and II antibody-verified eplet mismatch load, and PIRCHE-I and PIRCHE-II scores correlated negatively with both microchimerism presence and quantity. The correlation between mismatch parameters aimed at evaluating the risk of humoral and T cell-mediated allorecognition and foetal microchimerism was more evident postpartum than during pregnancy. The observed predictive effect of foetal-maternal histocompatibility on foetal microchimerism suggests that circulating foetal cells are subject to clearance by the maternal immune system. We propose that allorecognition of foetal cells in the maternal circulation and tissues influences any long-term effect that foetal microchimerism may have on maternal health.</p>","PeriodicalId":13172,"journal":{"name":"HLA","volume":"104 4","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/tan.15717","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142464143","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":"Identification of the Novel HLA-DQB1*06:432 Allele by Sequence-Based Typing","authors":"John Jeongseok Yang,&nbsp;Heung-Bum Oh","doi":"10.1111/tan.15731","DOIUrl":"10.1111/tan.15731","url":null,"abstract":"<div>\u0000 \u0000 <p>HLA-DQB1*06:432 differs from HLA-DQB1*06:09:01:01 by a nonsynonymous nucleotide substitution in codon 186, changing Valine to Methionine.</p>\u0000 </div>","PeriodicalId":13172,"journal":{"name":"HLA","volume":"104 4","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142464147","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":"Recognition of the HLA-B*55:39 Allele in a Taiwanese Individual","authors":"Kuo-Liang Yang,&nbsp;Py-Yu Lin","doi":"10.1111/tan.15718","DOIUrl":"10.1111/tan.15718","url":null,"abstract":"<div>\u0000 \u0000 <p>One nucleotide substitution in codon 118 of <i>HLA-B*55:02:01:01</i> results in a novel allele, <i>HLA-B*55:39.</i></p>\u0000 </div>","PeriodicalId":13172,"journal":{"name":"HLA","volume":"104 4","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142464149","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 the Novel HLA-A*33:03:68 Allele in a Chinese Platelet Donor","authors":"Fan Yang,&nbsp;Su-Qing Gao,&nbsp;Wen-Xia Xia,&nbsp;Yun-Ping Xu","doi":"10.1111/tan.15711","DOIUrl":"10.1111/tan.15711","url":null,"abstract":"<div>\u0000 \u0000 <p>The novel HLA-A*33:03:68 allele differs from HLA-A*33:03:01:01 by 1 variation in exon 3.</p>\u0000 </div>","PeriodicalId":13172,"journal":{"name":"HLA","volume":"104 4","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142464145","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 HLA-DPA1 Allele, HLA-DPA1*01:204, Was Identified by Next-Generation Sequencing","authors":"Xiong-jie He,&nbsp;Kun-Xiang Wang,&nbsp;Peng Zhang,&nbsp;Ti-Long Huang,&nbsp;Xian-Wen Zhang","doi":"10.1111/tan.15710","DOIUrl":"https://doi.org/10.1111/tan.15710","url":null,"abstract":"<div>\u0000 \u0000 <p><i>HLA-DPA1*01:204</i> has a single nucleotide substitution at position 426G &gt; T when compared to the <i>HLA-DPA1*01:03:01:15</i> allele.</p>\u0000 </div>","PeriodicalId":13172,"journal":{"name":"HLA","volume":"104 4","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142447610","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":"Paternal HLA-Derived Epitopes and Live Birth in Secondary Recurrent Pregnancy Loss: New Insights From a Clinical Trial","authors":"Maria Christine Krog,&nbsp;Emma T. M. Peereboom,&nbsp;Kirsten Geneugelijk,&nbsp;Benedict M. Matern,&nbsp;Astrid Marie Kolte,&nbsp;Ole Bjarne Christiansen,&nbsp;Rudi Steffensen,&nbsp;Henriette Svarre Nielsen,&nbsp;Eric Spierings","doi":"10.1111/tan.15723","DOIUrl":"https://doi.org/10.1111/tan.15723","url":null,"abstract":"<div>\u0000 \u0000 <p>Recurrent pregnancy loss (RPL), defined as two or more pregnancy losses before the 24th week of gestation, affects 1%–3% of women worldwide. Approximately, 40% of RPL cases are secondary RPL (sRPL), where women have given birth before facing pregnancy losses. The underlying causes of RPL remain unclear, but immune-related factors may play a role. Previously, a randomised controlled trial using immunoglobulin (IVIG) in sRPL women with a history of four pregnancy losses performed in our RPL unit did not show significant effects of IVIG treatment overall. Yet, some evidence suggests potential benefits for a subset of sRPL patients. In the cohort used for the randomised controlled trial, we examined the role of maternal HLA class II-presented fetal HLA-derived epitopes in sRPL using the predicted indirectly recognisable HLA epitopes (PIRCHE-II) algorithm. In the placebo group, sRPL mothers with an anti-HLA antibody response had higher PIRCHE-II scores when having a live birth compared with sRPL women who experienced another pregnancy loss. This difference was not observed in the IVIG-treated group. Furthermore, as a proxy for T-cell memory, the number of overlapping peptides between the two paternal haplotypes in couples having live births without treatment displayed a larger number of overlapping peptides. This effect was primarily driven by class II-derived peptides. These results suggest that specific combinations of sRPL mothers and fathers, particularly those with an anti-HLA antibody response, may generate higher PIRCHE-II scores, which could contribute to successful live births. Understanding these immune interactions may provide insights for personalised diagnostic and therapeutic strategies in sRPL.</p>\u0000 </div>","PeriodicalId":13172,"journal":{"name":"HLA","volume":"104 4","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142447839","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":"Characterisation of the Novel HLA-DRB1*16:79 Allele Using Short- and Long-Read Sequencing Technologies","authors":"Gabriela Andrade,&nbsp;Mayara Cunha,&nbsp;Romulo Vianna,&nbsp;Luís Cristóvão Porto,&nbsp;Danielle Secco","doi":"10.1111/tan.15724","DOIUrl":"https://doi.org/10.1111/tan.15724","url":null,"abstract":"<p>The novel <i>HLA-DRB1*16:79</i> allele, first described in an individual from Brazil.</p>","PeriodicalId":13172,"journal":{"name":"HLA","volume":"104 4","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142447562","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}