Antibody-mediated pathogenesis of chronic GVHD through DBY/HLA class II complexes and induction of a GVL effect
Rattachement africain : jp. Niveau de preuve : code pays fourni par la source.
Le résumé fourni par la source
Chronic graft-versus-host disease (cGVHD) is a multiorgan syndrome with clinical features resembling those of autoimmune diseases. Thus, understanding commonalities in the pathophysiology of cGVHD and autoimmune diseases, such as the presence of disease-risk HLA alleles, is imperative for developing novel therapies against cGVHD. Alloantibodies against H-Y antigens encoded on the Y-chromosome are well-described risk factors for cGVHD in female-to-male transplantation. However, because H-Y antigens generally localize intracellularly in the male reproductive organs, how they emerge at affected organ levels remains elusive. Here, by analyzing nationwide registry data stratified per donor-recipient sex, we identified specific HLA class II alleles that contributed to susceptibility to male cGVHD after transplantation from HLA-identical female siblings (HLA-DRB1∗15:02: hazard ratio, 1.28; 95% confidence interval, 1.03-1.58; P = .025). Coexpression of HLA-DRB1∗15:02 efficiently transported full-length H-Y antigens, especially DBY, to the surface. The presence of alloantibodies against DBY/HLA class II complexes significantly predicted the occurrence of cGVHD (68.8% vs 31.7% at 1 year; P = .002). Notably, the ability of HLA class II molecules to transport and present DBY to alloantibodies was closely associated with the susceptibility of HLA class II alleles to cGVHD. DBY specifically colocalized with HLA class II molecules on the dermal vascular endothelium in cGVHD and provoked complement-dependent cytotoxicity. Moreover, these complexes were observed in some male leukemic cells. Altogether, these findings suggest that vascular endothelial cells facilitate alloantibody-mediated cGVHD and highlight that alloantibodies against DBY/HLA class II complexes could be common targets for cGVHD and a graft-versus-leukemia effect.
Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.
Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Antibody-mediated pathogenesis of chronic GVHD through DBY/HLA class II complexes and induction of a GVL effect
- Date Crossref
- 14/09/2023
- Éditeur
- American Society of Hematology
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Jichi Medical University Department of Medicine pays non établi dans la noticeUniversité ou école supérieure
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Jichi Medical University Saitama Medical Center pays non établi dans la noticeÉtablissement de santé
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Tokyo Metropolitan Komagome Hospital Tokyo Metropolitan Cancer and Infectious Diseases Center pays non établi dans la noticeÉtablissement de santé
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Japanese Red Cross Nagoya Daiichi Hospital pays non établi dans la noticeÉtablissement de santé
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Kyushu University Hospital Oncology & Cardiovascular Medicine pays non établi dans la noticeÉtablissement de santé
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Hamanomachi Hospital pays non établi dans la noticeÉtablissement de santé
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Kobe City Medical Center General Hospital pays non établi dans la noticeÉtablissement de santé
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Osaka Metropolitan University pays non établi dans la noticeUniversité ou école supérieure
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Kyoto University pays non établi dans la noticeUniversité ou école supérieure
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Hiroshima University Research Institute for Radiation Biology and Medicine pays non établi dans la noticeUniversité ou école supérieure
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Aichi Medical University pays non établi dans la noticeUniversité ou école supérieure
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The Japanese Data Center for Hematopoietic Cell Transplantation pays non établi dans la noticeStructure de recherche
Department of Medicine — Jichi Medical University, Jichi Medical University Saitama Medical Center et Tokyo Metropolitan Cancer and Infectious Diseases Center — Tokyo Metropolitan Komagome Hospital, avec 9 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.