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Platelets from donors with consistent low HLA-B8, B12 or B35 expression do not undergo antibody-mediated internalization

Anno Saris, Bert Tomson, Anneke Brand, Arend Mulder, Frans H. Claas, Jos Lorinser, John Scharenberg, S. Marieke van Ham, Anja ten Brinke, Jaap Jan Zwaginga and Pieter F. van der Meer

Key points

  • HLA-B8, B12 or B35 expression on PLTs varies significantly between individuals and is consistently low or undetectable in certain donors.

  • Opsonization and antigen expression correlates with ab-mediated internalization of PLTs which is absent in PLTs with low antigen expression.

Abstract

Patients refractory to platelet transfusions due to alloimmunization require HLA-matched platelets, which is only possible if a large HLA-typed donor pool is available. However, even then patients with broad immunization or rare haplotypes may not have suitable donors. In these patients, transfusions with platelets showing low HLA class I expression may be an alternative for fully HLA matched transfusions. In this study, we quantified the proportion of donors with consistently low HLA-B8, B12, and B35 expression on platelets using human monoclonal antibodies specific for these antigens. Furthermore, as model for in vivo clearance, antibody-mediated internalization of these platelets by macrophages was investigated. The expression of HLA-B8, B12 or B35 on platelets was extremely variable between individuals (coefficients of variation: 41.4-73.6%). For HLA-B8, but not for B12 or B35, this variation was in part explained by zygosity. The variation was most pronounced in, but not exclusive to platelets. Expression within one donor was consistent over time. Remarkably, 32% of 113 HLA-B8, 34% of 98 HLA-B12 and 9% of 66 HLA-B35 donors showed platelet antigen expression that was not or only minimally above background. Antibody-mediated internalization of platelets by macrophages correlated with antibody opsonization and antigen expression, and was absent in platelets with low or minimal HLA expression. In conclusion, our findings indicate that a substantial proportion of donors show consistent low expression of specific HLA class I antigens on their platelets. These platelets may be used to treat refractory patients with antibodies directed against these particular antigens, despite HLA mismatches.

  • Submitted July 28, 2017.
  • Accepted October 20, 2017.