A HUMAN MONOCLONAL IGA AUTOANTIBODY-185 12 BEHAVES LIKE AN AUTOIMMUNEANTIPHOSPHOLIPID ANTIBODY/

A human monoclonal anticardiolipin autoantibody (ACA) of the IgA-k iso type, designated 185/ 12, is described. The antibody was prepared from peripheral B cells, obtained from a patient with a history of habitua l abortion, by immortalization with Epstein-Barr virus (EBV). The anti body displays a strong binding activity to cardiolipin and phosphatidy l L-serine, but not to phosphatidylcholine, phosphatidylinositol, ssDN A and dsDNA. It binds to cardiolipin in a concentration-related and sa turable manner (K-d = 3.0X10(-8) M). This reaction is dependent upon t he presence of bovine serum, and is fully inhibited by cardiolipin ves icles. The 185/12 antibody exhibits different binding patterns to the solid-phase bound cardiolipin-serum complex and to its individual comp onents (cardiolipin and bovine serum). The B-max of 185/12 binding to the complex (0.968 OD units) is higher than the sum of the B-max value s calculated for each one of the complex components (0.352 + 0.179 = 0 .531 OD units). Bovine serum as well as purified beta(2)-glycoprotein I (beta(2)-GPI) in suspension inhibit the binding of 185/12 to the com plex. 185/12 binding capacity increases in direct relation to the risi ng concentration of beta(2)-GPI, Collectively, these data may be inter preted to suggest that 185/12 antibody, which is an IgA isotype, exhib its characteristics usually attributed only to antiphospholipid autoan tibodies (APA) of the IgG isotype, that are associated with the clinic al spectrum of APA syndrome (APA-S). It is, therefore, possible that a utoantibodies of the IgA isotype could play a pathogenic role, which m ay be different from that of the IgG isotype, in the development of au toimmune phenomena.