Summary
This study was undertaken to analyze antibodies to protein S (PS) in patients with
an acquired PS deficiency. Plasma from symptomatic patients with acquired (n = 14)
or congenital (n = 10) PS deficiency and 10 healthy donors was screened for PS antibodies
by immunoblotting and for anti-phospholipid antibodies. PS antibodies (IgG) were detected
in five of the patients with acquired PS deficiency. These antibodies belonged to
the G1 and G4 immunoglobulin subclasses. IgG fractions from the same 5 patients were
shown to inhibit PS activity. The inhibition of PS activity by the 5 IgG fractions
was shown to be time-and dose-dependent and was abolished following incubation with
purified PS, while no effect was found after absorption with cardiolipin micelles.
In addition, anticardiolipin monoclonal or human purified antibodies, failed to exert
significant PS inhibition. These findings demonstrate that anti-PS antibodies are
able to inhibit PS activity and that this is independent of anti-phospholipid antibodies.
Given the clinical features of the patients, these antibodies should be regarded as
an expression of the broad autoimmune syndrome involving the phospholipid-binding
plasma proteins.
