Clinical manifestations of the antiphospholipid syndrome in patients with systemic lupus erythematosus associate more strongly with anti-beta 2-glycoprotein-I than with antiphospholipid antibodies

Abstract

Objective: To investigate antibodies to phospholipid-free beta 2-glycoprotein-I (a beta 2 GP-I) in the serum of patients with systemic lupus erythematosus (SLE).

Methods: We studied alpha beta 2 GP-I by Western blot, dot blot, and ELISA in 94 patients with SLE. Twenty-one had antiphospholipid syndrome (APS) by clinical and serological criteria, 33 had neither of these features, 18 had the clinical criteria for APS but no serum antiphospholipid antibodies (aPL). and 22 had positive aPL but no related clinical manifestations. As controls, we also studied 76 normal sera. Sera were also inhibited with cardiolipin micelles and tested for anticardiolipin antibodies (aCL) or a beta GP-I activities.

Results: Thirty-five of 39 patients with SLE with clinical manifestations of APS has serum a beta 2 GP-I, while only 2 of 55 patients with SLE without such clinical manifestations had them (p = 0.000000001). Sixteen patients with SLE with clinical APS but aPL negative were a beta GP-I positive. All 35 patients with SLE who were a beta 2 GP-I positive had vascular manifestations, but these antibodies were present in only 4 of 55 patients with SLE without vascular manifestations (p = 0.00000001). No patient having either aPL or a beta 2 GP-I had clinical manifestations of APS, whereas all 19 patients positive for both antibodies had clinical APS. The a beta 2 GP-I positive, aPL negative patients with SLE had clinical APS more frequently (16/18) than did a beta GP-I negative, aPL positive patients with SLE (2/24) (p = 0.000000001). The association of clinical manifestations of APS with a beta 2 GP-I was stronger than with aPL. Inhibition studies also indicate that aPL and a beta 2 GP-I are 2 different antigen/antibody systems.

Conclusions: Our findings indicate that the so called APS associates strongly with antibodies recognizing phospholipid-free beta 2 GP-I. There are patients' sera that also recognize cardiolipin and/or its cofactor beta 2 GP-I, the latter perhaps by reacting with a neoepitope on this protein that appears after its interaction with cardiolipin. These would be the previously considered (beta 2 GP-I dependent) aCL.