Fiche publication
Date publication
septembre 2025
Journal
Haematologica
Auteurs
Membres identifiés du Cancéropôle Est :
Pr FORNECKER Luc-Matthieu
Tous les auteurs :
Couvidou A, Wald M, Angénieux C, Pires-Marafon J, Apithy MJ, Humbrecht C, Fornecker LM, Congy-Jolivet N, Dupuis A, Rollin J, Maître B
Lien Pubmed
Résumé
Patients requiring recurrent platelet transfusions are subject to platelet transfusion refractoriness (PTR), a therapeutic failure due to rapid clearance of transfused platelets from the circulation. One major cause of PTR is the presence in the recipient of multiple IgG directed against allogeneic HLA Class-I (HLA-I) molecules expressed by the donor platelets. Strikingly, the presence of anti-HLA-I IgG does not necessarily correlate with PTR, thus questioning the role of the antibody properties themselves. Using blood of HLA-I alloimmunized patients with or without PTR, we identified the subclasses of their anti-HLA-I IgG. We found the distribution of these subclasses to be different according to patients, with IgG1 being predominant in non-PTR patients while IgG1 in combination with IgG2 or IgG3 were detected in PTR patients. To understand the mechanisms associated with PTR, we used human chimeric pan-HLA-I IgG1, IgG2, or IgG3 antibodies and assessed the functional implications of these human IgG subclasses on platelet activation. We showed that each subclass led to platelet aggregation, P-selectin exposure and Annexin V binding. However, we found that the mechanisms of platelet activation differed between subclasses. Specifically, we discovered that pan-HLA-I hIgG2-induced platelet activation was CD32a dependent, while hIgG1- and hIgG3-induced platelet activation relied on complement recruitment. Hence, this study may have direct implications for hierarchizing pathogenic anti-HLA-I alloantibodies in highly polyimmunized patients and be a valuable aid in selecting suitable treatments, particularly by streamlining the search for functionally compatible platelet components.
Référence
Haematologica. 2025 09 18;:
