Ahmed Gaballa, Anna Söderström, Nina Lundin, Torsten Eich
{"title":"Next-Generation Sequencing Reveals the Novel HLA-DQA1*06:01:04 Allele in a Bone Marrow Donor","authors":"Ahmed Gaballa, Anna Söderström, Nina Lundin, Torsten Eich","doi":"10.1111/tan.15729","DOIUrl":"10.1111/tan.15729","url":null,"abstract":"<div>\u0000 \u0000 <p>A single nucleotide mismatch within exon 2 of HLA-DQA1 differentiates the novel <i>DQA1*06:01:04</i> allele from <i>DQA1*06:01:01:01</i>.</p>\u0000 </div>","PeriodicalId":13172,"journal":{"name":"HLA","volume":"104 4","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142499439","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}
Jiyong Zhou, Yi Duan, Ke Yuan, Zhihui Feng, Xiuxiang Liu
{"title":"Genomic full-length sequence of the HLA-B*40:96 allele was identified by full length group-specific sequencing","authors":"Jiyong Zhou, Yi Duan, Ke Yuan, Zhihui Feng, Xiuxiang Liu","doi":"10.1111/tan.15686","DOIUrl":"10.1111/tan.15686","url":null,"abstract":"<p>Genomic full-length sequence of <i>HLA-B*40:96</i> was identified by a group-specific sequencing approach in a Chinese individual.</p>","PeriodicalId":13172,"journal":{"name":"HLA","volume":"104 4","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142499436","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}
Jian-Ping Li, Xu Zhang, Feng-Qiu Lin, Xiao-Feng Li
{"title":"Detection of the Novel HLA-B*15:358 Allele by Sanger Dideoxy Nucleotide Sequencing","authors":"Jian-Ping Li, Xu Zhang, Feng-Qiu Lin, Xiao-Feng Li","doi":"10.1111/tan.15736","DOIUrl":"10.1111/tan.15736","url":null,"abstract":"<div>\u0000 \u0000 <p><i>HLA-B*15:358</i> differs from <i>HLA-B*15:02:01:01</i> by one nucleotide substitution at position 685 in exon 4.</p>\u0000 </div>","PeriodicalId":13172,"journal":{"name":"HLA","volume":"104 4","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142499433","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}
Yogini Mujumdar, Shramika Vasant Thakur, Deepika Baban Talge, Vikrant M. Bhor, Itta Krishna Chaaithanya
{"title":"Identification of the Novel Non-classical HLA-G*01:24:02 Allele by Next-Generation Sequencing","authors":"Yogini Mujumdar, Shramika Vasant Thakur, Deepika Baban Talge, Vikrant M. Bhor, Itta Krishna Chaaithanya","doi":"10.1111/tan.15728","DOIUrl":"10.1111/tan.15728","url":null,"abstract":"<div>\u0000 \u0000 <p><i>HLA-G*01:24:02</i> differs from <i>HLA-G*01:01:03:03</i> by one nucleotide substitution in codon 304 in exon 5.</p>\u0000 </div>","PeriodicalId":13172,"journal":{"name":"HLA","volume":"104 4","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142499438","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 Two New HLA Alleles: HLA-C*04:524 and -DQB1*03:524","authors":"Maria Loginova, Igor Paramonov","doi":"10.1111/tan.15726","DOIUrl":"10.1111/tan.15726","url":null,"abstract":"<p>Two new alleles were identified during routine next generation sequencing.</p>","PeriodicalId":13172,"journal":{"name":"HLA","volume":"104 4","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142499432","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}
Kazutoyo Osoegawa, Kenneth Yim, Megan Jeracki, Tuan-Nghia Nguyen, Lin Wang, Andrew Cho, Rhidina David, Jellina Son, Arianne Mankey, Steven G. E. Marsh, Ketevan Gendzekhadze, Cathi Murphey, Marcelo A. Fernández Viňa
{"title":"A new strategy for systematically classifying HLA alleles into serological specificities: Update and refinement","authors":"Kazutoyo Osoegawa, Kenneth Yim, Megan Jeracki, Tuan-Nghia Nguyen, Lin Wang, Andrew Cho, Rhidina David, Jellina Son, Arianne Mankey, Steven G. E. Marsh, Ketevan Gendzekhadze, Cathi Murphey, Marcelo A. Fernández Viňa","doi":"10.1111/tan.15702","DOIUrl":"10.1111/tan.15702","url":null,"abstract":"<p>HLA antigens were historically defined according to the unique reactivity pattern of cells expressing HLA molecules with distinctive clusters of allo-antisera and/or monoclonal antibodies. Subsequently, amino acid residues determining epitopes (DEP) in the HLA molecule were correlated with reactivity patterns. In current clinical practice, the presence of allo-antibodies is assessed using Luminex-based solid phase single antigen bead (SAB) assays for transplantation. Recently, novel antigens were proposed for HLA molecules with DEP patterns that do not match any serologically defined antigens recognised by the WHO Nomenclature Committee. To validate the antigens, mean fluorescence intensity values of SABs tested on >13,000 patients' sera were extracted from clinical databases and analysed by scatter plots using a linear regression model. We found that when two proteins were considered as the same antigen in the original study, for example, HLA-A*02:01 and -A*02:06, their correlation ranked among the highest values at each locus. In contrast, discrete asymmetric outliers were observed when there were different antigens, for example, HLA-A*30:01 and -A*30:02, allowing validation and confirmation of 20 novel antigens for HLA-A, -B, -C and -DR. The outliers were confirmed to be true or false by flow cytometric crossmatches. In addition to the previously defined residues for antigen assignments, findings suggest that further distinction should be made for common antigens by including the substitutions at residue 67 of HLA-B, 67 and 74 of -DR. These serologic analyses can be applied systematically to identify and confirm novel antigens. These developments will lead to designing optimal SAB panels and further improving virtual donor-specific antibodies assessment.</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.15702","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142464142","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*03:01:01:69 Allele in a Candidate Bone Marrow Donor by Next Generation Sequencing","authors":"Diamanto Kouniaki, Alexandra Tsirogianni","doi":"10.1111/tan.15741","DOIUrl":"10.1111/tan.15741","url":null,"abstract":"<div>\u0000 \u0000 <p>The <i>HLA-DQB1*03:01:01:69</i> allele differs from <i>HLA-DQB1*03:01:01:03</i> by a single nucleotide substitution in intron 2.</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":"142464146","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 Candidate Immunodominant Epitopes and Their HLA-Binding Prediction on BK Polyomavirus Proteins in Healthy Donors","authors":"Ana Gabriela Lara-de-León, Rut Mora-Buch, Ester Cantó, Cleofé Peña-Gómez, 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}
Emma T. M. Peereboom, Renato de Marco, Kirsten Geneugelijk, Jasvir Jairam, Frans M. Verduyn Lunel, Anna J. Blok, José Medina-Pestana, Maria Gerbase-DeLima, Arjan D. van Zuilen, Eric Spierings
{"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, Renato de Marco, Kirsten Geneugelijk, Jasvir Jairam, Frans M. Verduyn Lunel, Anna J. Blok, José Medina-Pestana, Maria Gerbase-DeLima, Arjan D. van Zuilen, 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> < 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}
Naser El-Lagta, Linh Truong, Felipe Ayora, Fredrick Mobegi, Samuel Bruce, Patricia Martinez, Lloyd D'Orsogna, Dianne De Santis
{"title":"Revolutionising High Resolution HLA Genotyping for Transplant Assessment: Validation, Implementation and Challenges of Oxford Nanopore Technologies' Q20+ Sequencing","authors":"Naser El-Lagta, Linh Truong, Felipe Ayora, Fredrick Mobegi, Samuel Bruce, Patricia Martinez, Lloyd D'Orsogna, 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}