Factor VII/VIIa: a new antigen in the anti-phospholipid antibody syndrome

We investigated antibodies to factor VII/VIIa (FVII/VIIa) and five other common target antigens in 33 patients with a history of anti-phospholipid syndrome (APS) and 50 healthy controls using an enzyme-linked immunosorbent assay (ELISA) technique. We found that antibody to FVII/VIIa, a previously unrecognized and common antigen in APS, was present in 67% of patients. Frequencies of antibodies to other target antigens were: anti-beta-2 glycoprotein 1 (anti-beta 2GP1), 88%; anti-cardiolipin (anti-CL), 76%; anti-phosphatidylethanolamine (anti-PE), 67%; anti-phosphatidylserine (anti-PS), 64%; and anti-phosphatidylcholine (anti-PC), 59%. Most patients had antibodies against multiple antigens, but a few were positive for only anti-beta 2GP1 (12%) or anti-CL (3%). Positivity for anti-FVII/VIIa was significantly associated with positivity for anti-PE, anti-PS and/or anti-PC (P < 0.05) but not anti-beta 2GP1. When frequencies of immunoglobulin G (IgG) versus immunoglobulin M (IgM) antibodies were compared, anti-beta 2GP1 IgG correlated with the lupus anticoagulant (P < 0.05) and was significantly more prevalent than IgM, but the reverse was seen for all other antigens. In arterial thrombosis, IgM was more prevalent for all antigens, and was significantly associated with FVII/VIIa, PE and PS, whereas in venous thrombosis, IgG was frequently prevalent, especially in association with FVII/VIIa, beta 2GP1 and CL. In summary, FVII/VIIa is a new and common antigen in APS. Anti-FVII/VIIa is often associated with anti-PE, anti-PS and anti-PC. The IgM class is more frequently associated with arterial thrombosis and the IgG class with venous thrombosis.