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Platelet‐associated antibodies, cellular immunity and FCGR3a genotype influence the response to rituximab in immune thrombocytopenia
Author(s) -
Cooper Nichola,
Stasi Roberto,
CunninghamRundles Susanna,
Cesarman Ethel,
McFarland Janice G.,
Bussel James B.
Publication year - 2012
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 - 10.1111/j.1365-2141.2012.09184.x
Subject(s) - rituximab , immunology , medicine , autoantibody , antibody , clone (java method) , cd8 , immune system , platelet , hematology , megakaryocyte , b cell activating factor , b cell , biology , gene , biochemistry , genetics , stem cell , haematopoiesis
Summary Rituximab is widely used in autoimmune diseases including immune thrombocytopenia ( ITP ), although the mechanism of effect remains unclear. This study describes the effects of rituximab on platelet‐associated antibodies ( PA ‐ APA s), B and T cell counts and clonality ( IGHV and TRG@ gene rearrangements), FCGR3A ( F cγ RIII a) and FCGR2A ( F cγ RII a) polymorphisms and correlation to anti‐ CD 40 ligand (CD40L) response. PA ‐ APA levels fell more frequently in responders (6/8) than in non‐responders (2/10: P = 0·08–0·15). Two responders had no PA ‐ APA s. Two non‐responders with a fall in PA ‐ APA s had very high CD 8 levels. One non‐responder had a B cell clone, one responder and one non‐responder had a T cell clone. 15/16 patients had the same responses to rituximab and anti CD 40 L . Patients with FCGR3A V / V polymorphisms were more likely to respond to rituximab ( P = 0·03). In summary, the fall in PA ‐ APA s in responders confirms the humoural effect of rituximab. Failure to respond in patients with very high CD 8 levels, despite PA ‐ APA fall indicates a role for T cell‐mediated platelet/megakaryocyte destruction. Concordance of response to anti‐ CD 40 L suggests autoantibody‐producing cells are under T cell control. Finally, the effect of FCGR polymorphisms on response confirms the importance of FCGR ‐mediated depletion of B cells in autoimmunity. This has implications on the pathology of ITP as well as the immunological effect of B cell depletion.