Altered Fc glycosylation of anti-HLA alloantibodies in hemato-oncological patients receiving platelet transfusions

Thijs L. J. van Osch, Tamas Pongracz, Dionne M. Geerdes, Juk Yee Mok, Wim J. E. van Esch, Jan Voorberg, Rick Kapur, Leendert Porcelijn, Jean-Louis H. Kerkhoffs, Pieter F. van der Meer, C. Ellen van der Schoot, Masja de Haas, Manfred Wuhrer, Gestur Vidarsson

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Background: The formation of alloantibodies directed against class I human leukocyte antigens (HLA) continues to be a clinically challenging complication after platelet transfusions, which can lead to platelet refractoriness (PR) and occurs in approximately 5%–15% of patients with chronic platelet support. Interestingly, anti-HLA IgG levels in alloimmunized patients do not seem to predict PR, suggesting functional or qualitative differences among anti-HLA IgG. The binding of these alloantibodies to donor platelets can result in rapid clearance after transfusion, presumably via FcγR-mediated phagocytosis and/or complement activation, which both are affected by the IgG-Fc glycosylation. Objectives: To characterize the Fc glycosylation profile of anti-HLA class I antibodies formed after platelet transfusion and to investigate its effect on clinical outcome. Patients/Methods: We screened and captured anti-HLA class I antibodies (anti-HLA A2, anti-HLA A24, and anti-HLA B7) developed after platelet transfusions in hemato-oncology patients, who were included in the PREPAReS Trial. Using liquid chromatography-mass spectrometry, we analyzed the glycosylation profiles of total and anti-HLA IgG1 developed over time. Subsequently, the glycosylation data was linked to the patients' clinical information and posttransfusion increments. Results: The glycosylation profile of anti-HLA antibodies was highly variable between patients. In general, Fc galactosylation and sialylation levels were elevated compared to total plasma IgG, which correlated negatively with the platelet count increment. Furthermore, high levels of afucosylation were observed for two patients. Conclusions: These differences in composition of anti-HLA Fc-glycosylation profiles could potentially explain the variation in clinical severity between patients.
Original languageEnglish
Pages (from-to)3011-3025
Number of pages15
JournalJournal of thrombosis and haemostasis
Issue number12
Early online date2022
Publication statusPublished - Dec 2022


  • HLA
  • alloimmunization
  • antibodies
  • glycosylation
  • platelet transfusion

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