Some authors have found a strong statistical association of antibodies to prothrombin (aPT) with thrombosis in patients with antiphospholipid syndrome (APS); others have not confirmed this finding. It is unknown if the detection of aPT, in addition to anticardiolipin (aCL) and anti-β2-glycoprotein-I (aβ2GP-I) antibodies, provides additional information in the clinical study of these patients. We studied 38 patients with primary antiphospholipid syndrome and 466 patients with systemic lupus erythematosus (SLE; 24 had a history of thrombosis and 69 had secondary APS). All were tested by ELISA for serum aPT (IgG and IgM) using irradiated and plain plates. We also detected aCL and anti-β2GP-I by ELISA. One hundred sera from clinically healthy individuals were used as controls.
Twenty-six percent and 11% primary APS sera were positive for IgG and IgM aPT, respectively, compared with 3% and 5% of controls (p < 0.001, both comparisons). We found no difference in the frequency of aPT in SLE patients and controls, but aPT were positive in 46% of lupus patients with a history of thrombosis (20% IgG, 33% IgM) and in 9% of those without thrombosis (6% IgG, 5% IgM;p < 0.001, both comparisons). Likewise, there was a significant difference in the frequency of aPT in SLE patients with (22%) or without (9%) secondary APS (p < 0.001). aPT titers decreased two- to sixfold when tested in plain plates. Thirty-five of 38 primary APS sera (92%) had IgG anti-β2GP-I and 12 (31%) had aCL. No patient had aPT as the only antibody. The higher binding of aPT on irradiated plates suggests that aPT recognize a hidden epitope exposed by negative surfaces. The higher frequency of aPT found in patients with primary APS, SLE with thrombosis, or with secondary APS may suggest concerted pathogenic actions with other autoantibodies, but the detection of aPT does not seem to be of clinical value.