Autoantibodies and autoantigens in chronic immune thrombocytopenic purpura.
Chronic immune thrombocytopenic purpura (ITP) is an autoimmune disorder in which antiplatelet autoantibodies bind to antigens on the surface of platelets, resulting in their destruction. The newer antigen-specific (phase III) assays can detect platelet-associated and plasma autoantibodies in approximately 75% and 50% of patients, respectively. Antiplatelet autoantibodies bind to both platelets and megakaryocytes and preliminary evidence suggests that they not only cause platelet destruction but can also decrease platelet production either by interfering with megakaryocyte proliferation/maturation or by causing intramedullary platelet destruction. Autoantibodies are capable of activating complement and causing platelet phagocytosis both in vitro and in vivo. Many platelet-associated and plasma autoantibodies from ITP patients are light chain-restricted, which suggests a clonal origin. Approximately 75% of platelet autoantigens are localized to either the platelet glycoprotein (GP) IIb/IIIa or Ib/IX complex. Inhibition of the binding of autoantibodies from several ITP patients by either another ITP autoantibody or by a monoclonal anti-GPIIb/IIIa antibody suggests that the antigenic repertoire in chronic ITP may be limited. Most autoantigens on GPIIb/IIIa appear to be conformational since they are dependent on the presence of divalent cations. A variety of new investigative techniques have localized a few autoantigens to specific regions of the cytoplasmic or extracellular regions of both GPIIb/IIIa and GPIb/IX.
McMillan
R
R
Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.
D016824:Antigens, Human Platelet / Q000276:immunology; D001323:Autoantibodies / Q000097:blood / Q000276:immunology* / Q000378:metabolism; D001324:Autoantigens / Q000097:blood / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D002908:Chronic Disease; D000939:Epitopes / Q000276:immunology; D006801:Humans; D010980:Platelet Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000276:immunology*
D016824:Antigens, Human Platelet; D001323:Autoantibodies; D001324:Autoantigens; D000939:Epitopes; D010980:Platelet Membrane Glycoproteins