Thibault Pajot, Vincent Elsermans, Isabelle Top, Julien Lion, Nicolas Guillaume
{"title":"Characterisation of the Novel HLA-DRB1*11:351 Allele by Sequencing-Based Typing","authors":"Thibault Pajot, Vincent Elsermans, Isabelle Top, Julien Lion, Nicolas Guillaume","doi":"10.1111/tan.70397","DOIUrl":"10.1111/tan.70397","url":null,"abstract":"<div>\u0000 \u0000 <p><i>HLA-DRB1*11:351</i> differs from <i>HLA-DRB1*11:04:01:01</i> by one nucleotide substitution in codon 229 in exon 5.</p>\u0000 </div>","PeriodicalId":13172,"journal":{"name":"HLA","volume":"106 3","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145069415","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}
Thibault Pajot, Isabelle Top, Julie Demaret, Vincent Elsermans
{"title":"Characterisation of the Novel HLA-C*05:312 Allele by Sequencing-Based Typing","authors":"Thibault Pajot, Isabelle Top, Julie Demaret, Vincent Elsermans","doi":"10.1111/tan.70398","DOIUrl":"10.1111/tan.70398","url":null,"abstract":"<div>\u0000 \u0000 <p><i>HLA-C*05:312</i> differs from <i>HLA-C*05:01:01:01</i> by one nucleotide substitution in codon 308 in exon 5.</p>\u0000 </div>","PeriodicalId":13172,"journal":{"name":"HLA","volume":"106 3","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145069399","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}
Jianrong Chen, Weiyi Fu, Jianmin Hu, Guorong Liao, YongGuang Liu
{"title":"Discovery of a Novel HLA-G Allele, HLA-G*01:64, by PolyseqOne and Oxford Nanopore Sequencing","authors":"Jianrong Chen, Weiyi Fu, Jianmin Hu, Guorong Liao, YongGuang Liu","doi":"10.1111/tan.70385","DOIUrl":"https://doi.org/10.1111/tan.70385","url":null,"abstract":"<div>\u0000 \u0000 <p>HLA-G*01:64 differs from HLA-G*01:04:01 by one nonsynonymous nucleotide substitution in codon 107 in exon 2.</p>\u0000 </div>","PeriodicalId":13172,"journal":{"name":"HLA","volume":"106 3","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145038307","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}
Charlène Bouthemy, Jean Milhès, Nicolas Congy-Jolivet
{"title":"Identification of the Novel HLA-B*51:428 Allele by Next-Generation Sequencing","authors":"Charlène Bouthemy, Jean Milhès, Nicolas Congy-Jolivet","doi":"10.1111/tan.70394","DOIUrl":"https://doi.org/10.1111/tan.70394","url":null,"abstract":"<div>\u0000 \u0000 <p><i>HLA-B*51:428</i> differs from <i>B*51:01:01</i> by one nucleotide substitution in codon 260 in exon 4.</p>\u0000 </div>","PeriodicalId":13172,"journal":{"name":"HLA","volume":"106 3","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145038308","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, Jellina Son, Kenneth Yim, Steven G. E. Marsh, Marcelo A. Fernández Viňa
{"title":"Replacements at Structural or Functional Dimorphisms 103, 109 and 167 Distinguish HLA Class I Serologically Defined Antigens","authors":"Kazutoyo Osoegawa, Jellina Son, Kenneth Yim, Steven G. E. Marsh, Marcelo A. Fernández Viňa","doi":"10.1111/tan.70387","DOIUrl":"https://doi.org/10.1111/tan.70387","url":null,"abstract":"<p>Amino acid variations in the HLA molecule may serve as part of serologic epitopes (residues determining epitopes: DEP) detected by allo-antibodies. In current clinical histocompatibility practices, the presence of anti-HLA donor-specific antibodies (DSA) is assessed by solid phase (SP) tests with single antigen bead (SAB) panels. The antigenic risk is assessed based on the mean fluorescence intensity (MFI) values corresponding to each SAB via virtual crossmatch (VXM). To improve the accuracy of the VXM, new Associated Antigens were proposed based on DEPs; however, the antigenicity of some DEPs remained uncertain. In the current study, highly complex reactive sera were selected, and the complexity was reduced by adsorption with magnetic beads or lymphocytes followed by acid/neutralisation processes. As a proof of concept, a patient's serum was enriched with SAB coated with HLA-A*01:01. The eluate was tested using SP-SAB and showed reactivity with the antigens HLA-A1, -A9 (excluding A2403), -A80, -B12 and -B76. This allowed for validation of the antibody enrichment process and identification of the serological equivalency of DEPs 167G and 167S shared by these antigens. We identified broadly reactive sera being positive with the SAB HLA-B*35:12 (103V) and negative with the other SAB HLA-B35 (103L). Allo-antibodies were enriched by the adsorption/elution procedure with lymphocytes expressing HLA-B*35:12 and with SABs coated with HLA-B*57:01. The SAB assay using one of the eluates showed an almost identical cross-reactivity pattern: positive with all HLA-B SABs bearing 103V and no reactivity with SABs bearing 103L, suggesting that the enriched antibodies reacted with epitope(s) shared by HLA-B*35:12 and HLA-B*57:01. Additional reactivity was detected with the SABs HLA-A32, -A74 and -Cw3. This allowed for identification of putative epitope(s) containing residues 103V and 109L. Another serum with positive reactivity to the SAB HLA-B*35:02 showed reactivity to almost all HLA-A SABs including -A*02:10 and was negative with other -A*02 and -A*69:01 SABs, suggesting that the involvement of 107G and 109F may define novel epitopes. These studies allowed us to propose 13 novel HLA-B Associated Antigens; DEPs 103 and 109 in HLA class I were fully included in HLA Allele To Serotype (HATS) software update that allowed for a more detailed serologic characterisation of all common HLA alleles in the world.</p>","PeriodicalId":13172,"journal":{"name":"HLA","volume":"106 3","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/tan.70387","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145038122","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":"De Novo HLA Antibodies Are Associated With an Increased Risk of Severe Acute Graft-Versus-Host Disease Following Unrelated Donor Haematopoietic Stem Cell Transplantation","authors":"Beatrice Valatkaite-Rakstiene, Rita Kviliute, Arturas Jakubauskas","doi":"10.1111/tan.70392","DOIUrl":"https://doi.org/10.1111/tan.70392","url":null,"abstract":"<div>\u0000 \u0000 <p>The clinical relevance of de novo HLA antibodies in haematopoietic stem cell transplantation (HSCT) is yet incompletely defined. This prospective, single-centre study recruited adult patients with malignant haematological diseases receiving their first unrelated donor HSCT. Serum samples from 124 patients were screened for HLA antibodies before and after HSCT. It was found that 29 out of 61 females (47.5%) and 8 out of 63 males (12.7%) had HLA antibodies prior to HSCT. After HSCT, 31 out of 37 patients retained HLA antibody positivity, whereas 72 out of 87 maintained HLA antibody negativity. The 21 remaining patients changed their status: six turned HLA antibody-negative, while 15 became HLA antibody-positive. No donor-specific HLA antibodies (DSA) were identified prior to HSCT. One patient generated a single DSA together with the batch of non-donor-specific HLA antibodies (NDSA) after HSCT. The remaining 14 patients developed only de novo NDSA. Univariable Cox regression analysis revealed that the presence of all de novo HLA antibodies was associated with an elevated risk of Grade III–IV aGVHD (<i>p</i> = 0.012; HR 3.286) at 180 days after HSCT and neared statistical significance for delayed neutrophil engraftment (<i>p</i> = 0.056; HR 3.836). Multivariate Cox regression analysis indicated that only de novo HLA antibodies are an independent prognostic factor for the increased incidence of Grade III–IV aGVHD. The limited size of our cohort and the varied range of haematological malignancies have limited confidence in our findings. Thus, additional data obtained from larger patient cohorts is essential for the correct evaluation of the clinical relevance of de novo DSA and NDSA on HSCT outcomes.</p>\u0000 </div>","PeriodicalId":13172,"journal":{"name":"HLA","volume":"106 3","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145038059","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}
Magali Devriese, Diego Amaya-Ramirez, Tina Meng, Hiroko Miyadera, Lisa Giraldo, Laurie Toullec, Cedric Usureau, Olivier Toutirais, Malika Smaïl-Tabbone, Dave Lowe, Jean Luc Taupin
{"title":"The Hunt for HLA-DQ Allogeneic Eplets Is Not Over: Four New Ones, Including a Cross-Chain Eplet","authors":"Magali Devriese, Diego Amaya-Ramirez, Tina Meng, Hiroko Miyadera, Lisa Giraldo, Laurie Toullec, Cedric Usureau, Olivier Toutirais, Malika Smaïl-Tabbone, Dave Lowe, Jean Luc Taupin","doi":"10.1111/tan.70386","DOIUrl":"https://doi.org/10.1111/tan.70386","url":null,"abstract":"<p>The target of an anti-HLA antibody is an epitope on the surface of the antigen, and in particular the polymorphic eplet of its core, which contains one or a few polymorphic residues accessible to the molecule surface. The HLA Eplet Registry database references more than 550 HLA eplets thus deduced from AA sequence alignments. However, not all eplets have yet been verified and this list is not exhaustive. We performed a systematic analysis of sequence alignment of DQ antigens, to identify polymorphic amino acids so far not proposed as candidate eplets. From this, we describe and validate 3 DQB1 eplets targeted by sera of organ-transplanted patients and explore a new eplet overlapping the DQA1*03 and DQB1*03 chains. Serum antibody profiles using LABScreen, Lifecodes and a complementary DQ Luminex single antigen bead panel all showed a concordant pattern incriminating these residues. Moreover, antibodies were adsorbed and eluted using human splenic mononuclear cells and HLA-DQ transfected murine cell clones, thereby validating these four eplets. Their localisation by 3D modelling revealed uncertain accessibility of some residues implicated. The protrusion and accessibility of an eplet on the HLA surface may ultimately not always be sufficient to predict antibody binding, since the dynamic flexibility of the molecule can modify these parameters. Our strategy, combining Luminex single antigen assays, cell adsorption/elution and in silico prediction of surface exposure, altogether concur to ascertaining the realness of candidate eplets in the highly complex HLA system.</p>","PeriodicalId":13172,"journal":{"name":"HLA","volume":"106 3","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/tan.70386","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145038060","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}
Laurent Abi-Rached, Pierre Faux, Julien Paganini, Jacques Chiaroni, Pierre Pontarotti, Julie Di Cristofaro
{"title":"HLA Class Ib and MICA/MICB Expression in Human Tissues and Cell Types: Reshuffling Immune Players","authors":"Laurent Abi-Rached, Pierre Faux, Julien Paganini, Jacques Chiaroni, Pierre Pontarotti, Julie Di Cristofaro","doi":"10.1111/tan.70390","DOIUrl":"https://doi.org/10.1111/tan.70390","url":null,"abstract":"<p>Abnormal expression of HLA class Ib, MICA and MICB molecules is associated with the evolution of pathological conditions and clinical settings. Here, we use RNA-sequencing data from two publicly-available projects, from different human organs and tissues and at single-cell level, to present their transcriptional expression throughout the human body, in comparison to that of <i>HLA class Ia, HLA class II,</i> their costimulatory molecules, and the main <i>HLA</i> transcription factors. Our analyses for 21 target genes reveal that median gene expression differs by orders of magnitude and that the classical/non-classical HLA distinction is not absolute for overall expression. Sixteen of the 21 target genes show correlated expressions, although careful analyses of individual expression patterns in tissues and organs highlight specificities. Tissue and organ expression patterns reveal that the lymphoid organs, lungs, and gastrointestinal tract organs display the highest expression of the <i>HLA</i> and <i>HLA-related</i> genes. At single-cell level, adipocytes, endothelial cells, and immune cells all have unexpectedly close expression patterns. The expression pattern of the 21 target genes in non-immune organs, such as the lung or colon, and in non-immune cells like adipocytes, questions the role of these organs and cell types in immune homeostasis and suggests additional, non-immune functions of these molecules. The lack of impact of the <i>HLA</i> transcription factors studied here on <i>HLA</i> regulation in non-immune tissues also supports a role for additional <i>HLA</i> transcription factors in these tissues. Finally, classical/non-classical HLA classification based on molecule structure and genetic polymorphism does not seem to extend to their expression.</p>","PeriodicalId":13172,"journal":{"name":"HLA","volume":"106 3","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/tan.70390","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145022079","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-DQA1*05:121 Allele by Next-Generation Sequencing","authors":"Chiara Sindici, Donatella Londero","doi":"10.1111/tan.70389","DOIUrl":"https://doi.org/10.1111/tan.70389","url":null,"abstract":"<div>\u0000 \u0000 <p>The <i>HLA-DQA1*05:121</i> allele differs from the <i>HLA-DQA1*05:05:01:01</i> allele by a single nucleotide in exon 3.</p>\u0000 </div>","PeriodicalId":13172,"journal":{"name":"HLA","volume":"106 3","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144929802","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}