GENERATION AND ANALYSIS OF AN IGG ANTIPLATETLET AUTOANTIBODY REVEALS UNUSUAL MOLECULAR-FEATURES

Although serum transfer studies implicate IgG anti-platelet autoantibo dies in the premature platelet destruction of idiopathic thrombocytope nic purpura (ITP), many characteristics of these putative pathogenic a utoantibodies remain unclear. The inability to obtain relevant monoclo nal autoantibodies from patients has prevented their molecular, geneti c and functional studies as a homogenous population. We have generated a monoclonal IgG anti-platelet alpha(IIb)beta(3) autoantibody (termed G1) from an ITP patient. G1 binds human platelets (both resting and a ctivated) and purified alpha(IIb)beta(3) with a K-d of 1.57 x 10(-8) M . G1 utilizes VH4 and V lambda 2 genes. The G1 VH region apparently ha s a 30 nucleotide insertion in its second complementarity determining region (CDR). Notably, somatic CDR insertion in the VH region has been observed only in one IgG rheumatoid factor, and not in any characteri zed polyreactive human autoantibodies reported in the literature. Comb ined, these data suggest G1 may be a disease-relevant autoantibody, Fu rther generation and study of monoclonal IgG anti-platelet antibodies are warranted to determine the significance of such unusual autoantibo dies in the immunopathogenesis of chronic ITP.