The antiphospholipid/cofactor syndromes: A primary variant with antibodies to beta 2-glycoprotein-I but no antibodies detectable in standard antiphospholipid assays

BACKGROUND: Most systemic lupus erythematosus (SLE) patients with two or more clinical manifestations of the antiphospholipid syndrome (APS) and negative antiphospholipid antibodies (aPL) have antibodies to beta(2)-glycoprotein-I (a beta(2)GP-I). Herein we describe a similar set of circumstances, but in patients without evidence of SLE. PATIENTS AND METHODS: We studied 6 patients with recurrent venous and/or arterial thromboses without aPL as detected by routine assays nor clinical or serological evidence of other autoimmune disease. Immunogloublin (Ig) G and IgM antibodies to bovine and human phospholipid-free beta(2)GP-I were studied by Western blot test and by enzyme-linked immunosorbent assay (ELISA) utilizing radiated and nonirradiated plates. We also tested antibodies to cardiolipin, phosphatidylserine, and phosphatidylethanolamine by ELISA. As controls, 54 normal sera were studied. RESULTS: All 6 patients had recurrent arterial and/or venous thromboses. Three also had thrombocytopenia, 1 had livedo reticularis, and 2 had valvular heart disease. None of the patients had aPL, but all had serum IgG reactivity against human and bovine beta(2)GP-I (P <0.001 versus controls for both). Titers of antibovine beta(2)GP-I were higher when studied in irradiated plates but were also higher than normal in nonirradiated plates (P <0.001). These antibodies did not recognize human or bovine beta(2)GP-I bound to cardiolipin in solid phase. We confirmed by Western blot that these autoantibodies recognize human beta(2)GP-I. We found no IgM a beta(2)GP-I. CONCLUSIONS: We describe a primary condition akin to the antiphospholipid syndrome with negative aPL, but with serum IgG antibodies to human and bovine beta(2)GP-I. These antibodies recognize beta(2)GP-I epitopes that are not accessible when beta(2)GP-I is bound to cardiolipin. (C) 1996 by Excerpta Medica, Inc.