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Antiphospholipid Antibodies Differ in aPL Cofactor Requirement

Hospital for Special Surgery, Cornell University Medical Center, 535 East 70th Street, New York, NY 10021, USA

Michael D. Lockshin

Hospital for Special Surgery, Cornell University Medical Center, 535 East 70th Street, New York, NY 10021, USA

Azzudin E. Gharavi

Hospital for Special Surgery, Cornell University Medical Center, 535 East 70th Street, New York, NY 10021, USA

Although autoimmune antiphospholipid antibodies (aPL) may require a serum cofactor, beta₂-glycoprotein I (ß₂GPI), for maximal binding in aPL ELISA, it is not known whether cofactor is absolutely required or is merely an enhancing factor for binding, nor is it clear whether aPL bind to cofactor itself, a cofactor-lipid complex, or a phospholipid modified in some way by cofactor. We therefore isolated and purified ß₂GPI and evaluated its relationship to both IgG and IgM aPL binding. aPL derived from different sera appear to have differing requirements for cofactor; the proportion of total binding attributable to cofactor varies from 46% to 95%. aPL do not bind to ß ₂GPI in the absence of phospholipid. Enhanced binding to phospholipid is seen if ß₂GPI is provided either before or with the test antibody. Autoimmune aPL bind phospholipid better with human rather than bovine cofactor. The requirement for cofactor is greater for low-avidity aPL as measured in an IgG-human cofactor system. Cofactor requirement alone does not predict the presence or absence of associated clinical complications.

Key Words: Antiphospholipid antibody • Lupus cofactor • aPL cofactor • ß2-glycoprotein I • Apolipoprotein H

Lupus, Vol. 1, No. 2, 83-90 (1992)
DOI: 10.1177/096120339200100205


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