ANTI-ß2GPI AUTOANTIBODIES RECOGNIZE AN EPITOE ON THE FIRST DOMAIN OF ß2GPI.

G. Michae Iverson, Edward J. Victoria and David M. Marquis

La Jolla Pharmaceutical Company, San Diego, California.

Anticardiolipin (aCL) autoantibodies are associated with thrombosis, recurrent fetal loss and thrombocytopenia. Only aCL found in autoimmune disease require the participation of the phospholipid binding plasma protein ß2-glycoprotein I (ß2GPI) for antibody binding and are now called anti-ß2GPI. The antigenic specificity of aCL affinity purified from 11 patients with high titers was evaluated in an effort to better understand the pathophysiology associated with aCL. Seven different recombinant domain-deleted mutants (DM) of human ß2GPI, and full length human ß2GPI (WT), were used in competition assays to inhibit the autoantibodies from binding to immobilized WT ß2GPI. Only those DMs that contained domain 1 inhibited the binding to immobilized WT ß2GPI from all the patients. The DMs that contained domain 1 inhibited all aCL in a similar, but not identical pattern, suggesting that these aCL recognize a similar, but distinguishable, epitope(s) present on domain 1.

Published in, Proc. Natl. Acad. Sci. USA, December, 1998, 95:15542-15546.