Zhong-Yu Kang, Wei Liu, Chun Liu, Xue-Ya Han, Dai-Hong Li
{"title":"Clinical Significance of Post-Transplant HLA Class II Donor-Specific Antibodies in the Development of Rejection and Clinical Outcomes in Paediatric Liver Transplantation: A Retrospective Single-Centre Study","authors":"Zhong-Yu Kang, Wei Liu, Chun Liu, Xue-Ya Han, Dai-Hong Li","doi":"10.1111/tan.70211","DOIUrl":"https://doi.org/10.1111/tan.70211","url":null,"abstract":"<div>\u0000 \u0000 <p>To evaluate the clinical relevance of post-transplant anti-HLA class II donor-specific antibodies (DSA) in paediatric liver transplantation (LT) recipients. We performed a retrospective cohort study including 346 paediatric patients who underwent LT between January 2019 and December 2022 at our centre. Based on the HLA class II DSA status, we divided the patients into the class II DSA-positive (<i>n</i> = 74) and class II DSA-negative (<i>n</i> = 272) groups. Demographic data, biopsy-proven rejection, DSA characteristics, clinical outcomes, and post-transplantation complications data were compared between groups. Our study consisted of 346 eligible paediatric LT recipients. Of these patients, 74 (21.4%) patients were positive for class II DSA and 272 (78.6%) were negative for class II DSA. The median and interquartile range between LT and class II DSA assessment was 12 (3–24) months post-transplant. Compared with the class II DSA-negative patients, post-transplant class II DSA was associated with a significantly increased risk of T cell-mediated rejection (<i>p</i> = 0.033) and antibody-mediated rejection (<i>p</i> = 0.045). Postoperatively, the incidence of cytomegalovirus infection (<i>p</i> = 0.003) and fungal infection (<i>p</i> = 0.007) was higher in the class II DSA-positive group than in the class II DSA-negative group. The frequency of adverse events, including biliary complications (<i>p</i> < 0.001) and intestinal flora alteration (<i>p</i> = 0.007), occurred more frequently in the class II DSA-positive group. Multivariable analyses showed that post-transplant class II DSA was an independent risk factor for T cell-mediated rejection (OR 2.027, 95% CI: 1.109–3.706, <i>p</i> = 0.022). Within the class II DSA-positive group, 22 (30.6%) patients developed T cell-mediated rejection post-transplant, 5 (6.9%) for DSA against HLA-DR, 12 (16.2%) for DSA against HLA-DQ, and 5 (6.7%) for DSA against HLA-DR + HLA-DQ. The MFI value for class II DSA was not significantly higher for patients with T cell-mediated rejection than for those without it. In conclusion, we demonstrated that the incidence of AMR among patients who developed class II DSAs after transplantation was higher than that of those who were negative for class II DSAs. Moreover, post-transplant class II DSA was an independent risk factor for post-transplantation TCMR. These results suggest that monitoring of class II DSA was a useful tool for paediatric LT recipients. However, due to the relatively small sample size of our study, further research with a larger sample size is needed for verification.</p>\u0000 </div>","PeriodicalId":13172,"journal":{"name":"HLA","volume":"105 5","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143930368","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}
Mireia Altadill, Iñaki Álvarez, Michelle Ataya, Gemma Heredia, Elisenda Alari-Pahissa, Aura Muntasell, Manuel Llano, Jonas Fuchs, Carlos Vilches, Hartmut Hengel, Anne Halenius, Miguel López-Botet
{"title":"Human Cytomegalovirus Antigen Presentation by HLA-G in Infected Cells","authors":"Mireia Altadill, Iñaki Álvarez, Michelle Ataya, Gemma Heredia, Elisenda Alari-Pahissa, Aura Muntasell, Manuel Llano, Jonas Fuchs, Carlos Vilches, Hartmut Hengel, Anne Halenius, Miguel López-Botet","doi":"10.1111/tan.70089","DOIUrl":"https://doi.org/10.1111/tan.70089","url":null,"abstract":"<p>HLA-E and -G class Ib molecules were considered unrelated to viral antigen presentation. HLA-E binds nonamers from the leader sequences of other HLA-I molecules and the human cytomegalovirus (HCMV) UL40 protein, interacting with CD94/NKG2 NK cell receptors. Yet, evidence that HLA-E may present some pathogen-derived peptides to CD8+ T lymphocytes has been reported. By contrast, HLA-G binds a broad spectrum of endogenous sequences but its role in antigen presentation is unknown. An experimental approach was set up to search for HCMV antigens displayed by HLA-G in infected cells. Among the analysed peptidome, 22 sequences corresponding to 16 HCMV molecules were identified; 17 peptides were confirmed to interact in vitro with HLA-G of which 10 displayed characteristic anchor residues. As compared to the response in short-term (6 h) assays to immunodominant IE-1 and pp65 antigens, none of the HLA-G-binding peptides stimulated cytokine production by CD8+ T cells from HCMV-seropositive blood donors (<i>n</i> = 15). Following a 14-day peptide stimulation of PBMC and expansion with IL-2, CD8+ T cells specifically responding to a subset of these viral antigens were detected in some individuals, yet were not restricted by HLA-G in functional assays. A subset of viral peptides did bind to both HLA-G and -E but were not recognised by CD94/NKG2 NK cell receptors. Our results provide the first evidence that HLA-G may display potentially immunogenic viral peptides in HCMV-infected cells, yet do not support their ability to promote HLA-G-restricted CD8+ T cell responses nor to modulate NK cell functions.</p>","PeriodicalId":13172,"journal":{"name":"HLA","volume":"105 5","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/tan.70089","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143930369","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}
Zhipan Wu, Ji He, Wei Zhang, Yanmin He, Faming Zhu
{"title":"Identification of the Novel HLA-C*03:641 Allele in a Chinese Cord Blood Donor","authors":"Zhipan Wu, Ji He, Wei Zhang, Yanmin He, Faming Zhu","doi":"10.1111/tan.70207","DOIUrl":"https://doi.org/10.1111/tan.70207","url":null,"abstract":"<div>\u0000 \u0000 <p>HLA-C*03:641 shows one nucleotide substitution when compared to HLA-C*03:02:02:01.</p>\u0000 </div>","PeriodicalId":13172,"journal":{"name":"HLA","volume":"105 5","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143930370","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":"Detection of the HLA-B*54:21 Allele, a Variant of B*54:01:01:01, in a Taiwanese Individual","authors":"Kuo-Liang Yang, Py-Yu Lin","doi":"10.1111/tan.70243","DOIUrl":"https://doi.org/10.1111/tan.70243","url":null,"abstract":"<div>\u0000 \u0000 <p>One nucleotide mutation in exon 2 of <i>HLA-B*54:01:01:01</i> results in the novel allele, <i>HLA-B*54:21</i>.</p>\u0000 </div>","PeriodicalId":13172,"journal":{"name":"HLA","volume":"105 5","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143925886","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}
Samir Agarwal, Shikha Kumari, Neha Bairagi, Manu Bamal, Umesh Kapoor
{"title":"Novel HLA-DQB1*06:525 Allele Identified Through Next-Generation Sequencing in a North Indian Individual","authors":"Samir Agarwal, Shikha Kumari, Neha Bairagi, Manu Bamal, Umesh Kapoor","doi":"10.1111/tan.70242","DOIUrl":"https://doi.org/10.1111/tan.70242","url":null,"abstract":"<div>\u0000 \u0000 <p>HLA-DQB1*06:525 differs from HLA-DQB1*06:03:01:01 by a single nucleotide in exon 3, resulting in a codon change from ATC→TTC.</p>\u0000 </div>","PeriodicalId":13172,"journal":{"name":"HLA","volume":"105 5","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143925962","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}
Frank Grünebach, Tobias B. Haack, Michaela Döring, Britta Merz, Antje Petz, Christine Bauer, Martina Storz, Peter Lang, Reinhild Klein
{"title":"Deletion of the HLA-B Gene in One of the Inherited Haplotypes in a Northern European Family","authors":"Frank Grünebach, Tobias B. Haack, Michaela Döring, Britta Merz, Antje Petz, Christine Bauer, Martina Storz, Peter Lang, Reinhild Klein","doi":"10.1111/tan.70234","DOIUrl":"https://doi.org/10.1111/tan.70234","url":null,"abstract":"<p>Targeted next generation sequencing-based <i>HLA</i> typing of a 17-year-old female transplant patient showed homozygosity for the <i>HLA-B</i> allele. The segregation analysis of HLA haplotypes of family members only allowed the conclusion that the B-allele was deleted in the haplotype inherited from the father and accordingly paternal grandfather, resulting in false homozygous genotyping. The subsequent whole-genome sequencing of the patient and her father confirmed an approximately 85 kb deletion at 6p21.33 from the 5′ end of the <i>HLA-B</i> to the 3′ end of the <i>HLA-C</i> gene extending telomeric to <i>HLA-C</i>.</p>","PeriodicalId":13172,"journal":{"name":"HLA","volume":"105 5","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/tan.70234","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143925888","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}
Viviane Albrecht, Madlen Pahlke, Jürgen Sauter, Christin Paech, Kathrin Putke, Alexander H. Schmidt, Vinzenz Lange, Anja Klussmeier
{"title":"Extensive Analysis of Genetic Diversity in HLA-DMA, HLA-DMB, HLA-DOA and HLA-DOB: Characterisation of 236 Novel Alleles","authors":"Viviane Albrecht, Madlen Pahlke, Jürgen Sauter, Christin Paech, Kathrin Putke, Alexander H. Schmidt, Vinzenz Lange, Anja Klussmeier","doi":"10.1111/tan.70231","DOIUrl":"https://doi.org/10.1111/tan.70231","url":null,"abstract":"<p><i>HLA-DMA</i>, <i>-DMB</i>, <i>-DOA</i> and <i>-DOB</i> are non-classical HLA Class II genes that play a crucial role in the selection of highly stable HLA Class II/peptide complexes on antigen-presenting cells. Although the genes were initially thought to have a limited diversity with less than 13 alleles per gene documented in the IPD-IMGT/HLA Database in 2022, recent studies suggest a potential impact of certain alleles on the outcome of hematopoietic cell transplantation. To gain a deeper understanding of allelic diversity, we sequenced <i>HLA-DMA</i>, <i>-DMB</i>, <i>-DOA</i> and <i>-DOB</i> of 1880 potential stem cell donors from Germany, Poland, Great Britain and Chile, achieving full-gene resolution. Remarkably, we identified 3968 previously undescribed sequences, including 28 distinct novel proteins. The observed allele frequencies were consistent across all studied populations with one dominating protein for each gene: <i>HLA-DMA*01:01</i> (> 77%), <i>HLA-DMB*01:01</i> (> 63%), <i>HLA-DOA*01:01</i> (> 97%) and <i>HLA-DOB*01:01</i> (> 77%). Notably, a much higher diversity was observed in full-genomic resolution. Finally, we submitted 51 distinct novel sequences for <i>HLA-DMA</i>, 58 for <i>HLA-DMB</i>, 80 for <i>HLA-DOA</i> and 47 for <i>HLA-DOB</i> to the IPD-IMGT/HLA Database. This comprehensive reference database update will not only simplify future genotyping of <i>HLA-DMA</i>, <i>-DMB</i>, <i>-DOA</i> and <i>-DOB</i> but will hopefully also enhance our understanding of the complex process of peptide selection and loading to the HLA Class II proteins.</p>","PeriodicalId":13172,"journal":{"name":"HLA","volume":"105 5","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/tan.70231","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143925890","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}
Jianing Yuan, Bin Xi, Zechang Shi, Xin Li, Mingrui Huo
{"title":"The Novel HLA-B Allele, HLA-B*35:629N Was Identified in a Chinese Individual","authors":"Jianing Yuan, Bin Xi, Zechang Shi, Xin Li, Mingrui Huo","doi":"10.1111/tan.70233","DOIUrl":"https://doi.org/10.1111/tan.70233","url":null,"abstract":"<div>\u0000 \u0000 <p>The HLA-B*35:629N allele differs from HLA-B*35:01:01:02 by one nucleotide substitution in codon 74 in exon 2.</p>\u0000 </div>","PeriodicalId":13172,"journal":{"name":"HLA","volume":"105 5","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143925887","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-C*05:37 Allele in a Taiwanese Individual","authors":"Kuo-Liang Yang, Py-Yu Lin","doi":"10.1111/tan.70232","DOIUrl":"https://doi.org/10.1111/tan.70232","url":null,"abstract":"<div>\u0000 \u0000 <p>One nucleotide substitution in codon 186 of <i>HLA-C*05:01:01:01</i> results in a novel allele, <i>HLA-C*05:37</i>.</p>\u0000 </div>","PeriodicalId":13172,"journal":{"name":"HLA","volume":"105 5","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143925889","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}