Antibodies to phospholipid-free beta 2-glycoprotein-I in patients with primary antiphospholipid syndrome

To investigate serum anti-beta 2-glycoprotein-I antibodies (a beta 2 GP-I) in patients with primary antiphospholipid syndrome (APS).

We studied a beta 2 GP-I by Western blot, dot blot, and ELISA in the sera of 15 patients with primary APS with high titers of immunoglobulin G (IgG) and/or immunoglobulin M (IgM) anticardiolipin antibodies (aCL) at the time of study and compared findings with the sera of 13 aCL positive patients with syphilis and 76 healthy controls. Sera were also inhibited with cardiolipin micelles and tested for aCL and a beta 2 GP-I activities.

Twelve patients with primary APS but no syphilis patient or control subject had IgG to phospholipid-free beta 2 GP-I (p < 0.0001) for both comparisons). The aCL activity was inhibited with cardiolipin micelles but this treatment had less effect on a beta 2 GP-I activity. We found no IgM a beta 2 GP-I in any serum. Nine of 14 patients had had lupus anticoagulant activity; 8 of these had a beta 2 GP-I.

Patients with primary APS frequently have IgG a beta 2 GP-I that appear to differ from aCL. If aCL present in patients with primary APS actually react with a phospholipid induced neoepitope on beta 2 GP-I, as recently proposed, patients with primary APS have autoantibodies against 2 epitopes on beta 2 GP-I. Lack of a beta 2 GP-I in patients with syphilis might also contribute to protection from developing the APS.