Some patients with antiphospholipid syndrome express hitherto undescribed antibodies to cardiolipin-binding proteins

Contrary to infective anticardiolpin (aCL) antibodies, autoimmune aCL antib odies react with phospholipids (PL) mainly via binding to the plasma glycop rotein cofactor beta (2)-Glycoprotein I (beta (2)GPI). While there is a wel l-documented link between the risk of thrombosis and the presence of beta ( 2)GPI-dependent anticardiolipin antibodies, the pathological impact of othe r antiphospholipid antibodies is less clear. By means of cardiolipin affini ty-chromatography, we isolated and identified 3 CL-binding proteins, comple ment component C4, complement factor H and a kallikrein-sensitive glycoprot ein, and tested for the presence of autoantibodies against these proteins i n patients with antiphospholipid syndrome (APS), systemic lupus erythematos us (SLE) and other autoimmune diseases. High titers of autoantibodies to C4 as compared to age- and sex-matched healthy controls were present in 3 of 26 patients with APS, and weak titers were found in 2 of 26 patients with S LE and in none of 26 patients with other autoimmune diseases. Autoantibodie s to complement factor H were found in 4 APS, 3 SLE and none of the other a utoimmune patients. Autoantibodies to kallikrein-sensitive glycoprotein wer e detected in 6 APS patients, 1 SLE patient, and 1 patient with another aut oimmune disease. A close relationship between these antibodies was found, s uggesting their origin from a common macromolecular complex. However, no re lationship with anti-P,GPI antibodies was found, with the three patients wi th higher levels of autoantibodies having a low titer of anti-P,GPI antibod ies. In conclusion, some patients with APS harbor circulating antibodies to other CL-binding proteins which might be useful to further characterize th ese patients.