The antiphospholipid/cofactor syndromes. II. A variant in patients with systemic lupus erythematosus with antibodies to beta 2-glycoprotein I but no antibodies detectable in standard antiphospholipid assays.

OBJECTIVE: After the initial description of the anticardiolipin syndrome inpatients with systemic lupus erythematosus (SLE), it became clear that phospholipids other than cardiolipin could also be involved, that there could also be a primary syndrome, and that protein cofactors participate in in vitro reactivity of the autoantibodies. We describe 5 patients with SLE with clinical manifestations of antiphospholipid syndrome (APS) but persistently negative antiphospholipid antibodies (aPL). In all their tested sera we found antibodies to phospholipid-free beta 2-glycoprotein I (a beta 2-GPI).

METHODS: We studied 5 patients with SLE with at least 2 clinical manifestations of APS with no serum aPL detected in routine assays. IgG and IgM a beta 2-GPI were studied by ELISA and by Western blot. We also tested for antibodies to phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine by ELISA. We studied 54 normal sera as controls.

RESULTS: Four patients had livedo reticularis, 2 had thrombocytopenia, 2 had hemolytic anemia, and one each had recurrent venous thromboses, repeated fetal loss, pulmonary arterial hypertension, and transverse myelitis. No patient had serum aPL, but all had high titers of IgG a beta 2-GPI (p < 0.001 vs controls). Reactivity found in ELISA was confirmed by Western blot.

CONCLUSION: We describe a variant of APS in patients with SLE with negative aPL but serum antibodies to beta 2-GPI.