Autoantibody‐mediated complement activation on platelets is a common finding in patients with immune thrombocytopenic purpura (ITP)
- 10 October 2011
- journal article
- research article
- Published by Wiley in European Journal of Haematology
- Vol. 88 (2), 167-174
- https://doi.org/10.1111/j.1600-0609.2011.01718.x
Abstract
Background: It is commonly accepted that antibody-mediated removal of platelets represents a major mechanism of platelet destruction in immune thrombocytopenic purpura (ITP). Although complement activation may participate in platelet clearance, frequency and specificity of complement activation have not yet been studied systematically in ITP. Patients and methods: We examined blood samples from 240 patients with ITP. Samples were assessed for the presence of free and bound platelet autoantibodies by a standard glycoprotein-specific assay (monoclonal antibody-specific immobilization of platelet antigens). The ability of all sera to fix complement to a panel of human platelets was investigated in a complement fixation (CF) assay. Fixation of C1q to isolated GP IIb/IIIa was assessed by flow cytometry. Results: Glycoprotein-specific autoantibodies were detected as platelet-bound antibodies in 129 (54%) and as additional free antibodies in 26 (11%) and were undetectable in 111 (46%) patients. Assessing these subgroups for CF, 103 (65%), 21 (81%), and 33 (30%) sera gave positive results. If GP IIb/IIIa was absent from the test platelets, 81 (67%) lost their ability to fix complement; if GP Ib/IX was absent, 37 (30%) lost their ability to fix complement. C1q fixation to immunobeads coated with GP IIb/IIIa was observed in 50% of sera containing anti-GP IIb/IIIa antibodies. Conclusions: In a significant number of patients with chronic ITP, platelet autoantibodies are capable of activating the classical complement pathway. CF is even present in ITP sera without detectable autoantibodies, indicating that current techniques for autoantibody detection may be insufficient. The major targets for complement-fixing autoantibodies in ITP are GP IIb/IIIa and GP Ib/IX.Keywords
This publication has 33 references indexed in Scilit:
- Complement activation on platelets correlates with a decrease in circulating immature platelets in patients with immune thrombocytopenic purpuraBritish Journal of Haematology, 2010
- The ITP syndrome: pathogenic and clinical diversityBlood, 2009
- Expression of complement components and inhibitors on platelet microparticlesPlatelets, 2008
- Blood platelets activate the classical pathway of human complementJournal of Thrombosis and Haemostasis, 2006
- Platelet activation leads to activation and propagation of the complement systemThe Journal of Experimental Medicine, 2005
- T-cell-mediated cytotoxicity toward platelets in chronic idiopathic thrombocytopenic purpuraNature Medicine, 2003
- Guidelines for the investigation and management of idiopathic thrombocytopenic purpura in adults, children and in pregnancyBritish Journal of Haematology, 2003
- International study to compare antigen‐specific methods used for the measurement of antiplatelet autoantibodiesBritish Journal of Haematology, 1997
- Complement activation in vitro by antiplatelet antibodies in chronic immune thrombocytopenic purpuraBritish Journal of Haematology, 1986
- Post‐transfusion Purpura: a Serological and Immunochemical StudyBritish Journal of Haematology, 1981