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Monoclonal antibody‐mediated inhibition of the human HLA alloimmune response to platelet transfusion is antigen specific and independent of Fcγ receptor‐mediated immune suppression
Author(s) -
Crow Andrew R.,
Freedman John,
Hannach Barbara,
Lazarus Alan H.
Publication year - 2000
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.2000.02179.x
Subject(s) - immunology , monoclonal antibody , human leukocyte antigen , antigen , immune system , platelet , antibody , isoantibodies , receptor , medicine
Presensitization of donor platelets with allo‐specific immunoglobulin (Ig)G results in a diminished immune response against subsequent transfusions of platelets. To understand better the mechanism of how alloantibody presensitization results in a decreased alloimmune response, we have used murine monoclonal antibodies directed to polymorphic and non‐polymorphic regions of human leucocyte antigen (HLA) as well as platelet‐specific molecules. Here, we demonstrated that presensitization with anti‐human HLA class I antibodies, as well as β 2 ‐microglobulin‐specific antibody, protected against alloantibody production to five subsequent untreated platelet challenges. Use of complement fixing, non‐fixing or F(ab′) 2 fragments of HLA‐specific antibody also resulted in complete inhibition of alloantibody production. This protection was not seen when the platelets were presensitized with monoclonal antibodies to CD42a (GPIX), CD32 (low‐affinity IgG/Fcγ receptor) or murine IgG and was thus independent of B‐cell FcγRII‐mediated immune suppression. The inhibition observed was independent of HLA alloantigenic specificity as antibodies directed at the β 2 ‐microglobulin portion of HLA class I were as effective as antibodies against any of the HLA‐α regions (either polymorphic or non‐polymorphic) of class I. This work demonstrates that monoclonal antibody‐mediated suppression of the human HLA alloimmune response to platelet transfusion is antigen specific and is independent of FcγRII‐mediated immune regulation, complement fixing or HLA alloantigenic specificity.