title: Autoantibody-mediated complement activation on platelets is a common finding in patients with immune thrombocytopenic purpura (ITP).
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.
  
  
  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.
authors: Institute for Clinical Immunology and Transfusion Medicine, Justus Liebig University, Giessen, Germany.
authors: Abderrahim
authors: A
authors: Najaoui
authors: Tamam
authors: T
authors: Bakchoul
authors: Johanna
authors: J
authors: Stoy
authors: Gregor
authors: G
authors: Bein
authors: Mathias J
authors: MJ
authors: Rummel
authors: Sentot
authors: S
authors: Santoso
authors: Ulrich J
authors: UJ
authors: Sachs
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000918:Antibody Specificity; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D001792:Blood Platelets / Q000276:immunology / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D003167:Complement Activation / Q000276:immunology*; D015922:Complement C1q / Q000276:immunology / Q000378:metabolism; D005260:Female; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000276:immunology / Q000378:metabolism; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000175:diagnosis / Q000276:immunology*; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D006680:HLA Antigens; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D015922:Complement C1q