TY - JOUR
T1 - Platelets from donors with consistently low HLA-B8,-B12, or-B35 expression do not undergo antibody-mediated internalization
AU - Saris, Anno
AU - Tomson, Bert
AU - Brand, Anneke
AU - Mulder, Arend
AU - Claas, Frans H.
AU - Lorinser, Jos
AU - Scharenberg, John
AU - van Ham, S. Marieke
AU - ten Brinke, Anja
AU - Zwaginga, Jaap Jan
AU - van der Meer, Pieter F.
N1 - © 2018 by The American Society of Hematology.
PY - 2018/1/4
Y1 - 2018/1/4
N2 - 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
AB - 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
KW - Blood Platelets/immunology
KW - HLA-B Antigens/immunology
KW - HLA-B35 Antigen/immunology
KW - HLA-B8 Antigen/immunology
KW - Histocompatibility Testing
KW - Humans
KW - Isoantibodies/immunology
KW - Macrophages/immunology
KW - Patient Selection
KW - Platelet Transfusion/standards
KW - Tissue Donors
U2 - https://doi.org/10.1182/blood-2017-07-799270
DO - https://doi.org/10.1182/blood-2017-07-799270
M3 - Article
C2 - 29092829
SN - 0006-4971
VL - 131
SP - 144
EP - 152
JO - Blood
JF - Blood
IS - 1
ER -