Platelets from donors with consistently 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, Pieter F. van der Meer

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20 Citations (Scopus)

Abstract

Patients refractory to platelet transfusions because of 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 to 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% to 73.6%). For HLA-B8, but not for HLA-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 have platelets with consistently low expression of specific HLA class I antigens. These platelets may be used to treat refractory patients with antibodies directed against these particular antigens, despite HLA mismatches
Original languageEnglish
Pages (from-to)144-152
Number of pages9
JournalBlood
Volume131
Issue number1
Early online date2017
DOIs
Publication statusPublished - 4 Jan 2018

Keywords

  • Blood Platelets/immunology
  • HLA-B Antigens/immunology
  • HLA-B35 Antigen/immunology
  • HLA-B8 Antigen/immunology
  • Histocompatibility Testing
  • Humans
  • Isoantibodies/immunology
  • Macrophages/immunology
  • Patient Selection
  • Platelet Transfusion/standards
  • Tissue Donors

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