Significance of antiprothrombin antibodies in patients with systemic lupus erythematosus: clinical evaluation of the antiprothrombin assay and the antiphosphatidylserine/prothrombin assay, and comparison with other antiphospholipid antibody assays

Abstract

Antibodies against prothrombin are detected by enzyme immunoassays (EIA) in sera of patients with antiphospholipid syndrome (APS). However, there are two methods for antiprothrombin EIA; one that uses high binding plates (aPT-A), and another that utilizes phosphatidylserine bound plates (aPS/PT). We aimed to evaluate and compare aPT-A and aPS/PT in a clinical setting. We performed EIA for anti-PT, anti-PS/PT, IgG, and IgM anticardiolipin antibodies (aCL), and IgG beta2-glycoprotein I-dependent aCL (abeta2GPI/CL) with serum samples from 139 systemic lupus erythematosus (SLE) patients (16 with history of at least one thrombotic episode) and 148 controls. We observed that: (1) although titers of anti-PT and anti-PS/PT were significantly related with each other (P < 0.0001, rho = 0.548), titer of anti-PT and anti-PS/PT differed greatly in some samples; (2) odds ratio and 95% confidence interval for each assay was 3.556 (1.221-10.355) for aPT-A, 4.591 (1.555-15.560) for aPS/PT, 4.204 (1.250-14.148) for IgG aCL, 1.809 (0.354-9.232) for IgM aCL, and 7.246 (2.391-21.966) for abeta2GPI/CL. We conclude that, while all EIA performed in this study except IgM aCL are of potential value in assessing the risk of thrombosis, aPS/PT and abeta2GPI/CL seemed to be highly valuable in clinical practice, and that autoantibodies detected by anti-PT and anti-PS/PT are not completely identical.

Fig. 1

Values of antiphospholipid antibodies as measured by enzyme immunoassays in patients with systemic lupus erythematosus. One hundred and thirty-nine patients with systemic lupus erythematosus were divided into two groups (patients with or without history of thrombosis) and were applied to various antiphospholipid antibody enzyme immunoassays. Values are in arbitrary units determined independently for each enzyme immunoassay. Numbers above indicate P values calculated by Mann-Whitney U-test aPT-A, antiprothrombin antibody measured using high binding plates; aPS/PT, antiphosphatidylserine/prothrombin antibody; aCL, anticardiolipin antibody; aβ2GPI/CL, β2 glycoprotein I-dependent anticardiolipin antibody

Fig. 2a,b

Relationship between values of antiprothrombin antibody and antiphosphatidylserine/prothrombin antibody in sera of patients with systemic lupus erythematosus. The values of antiprothrombin antibody and antiphosphatidylserine/prothrombin antibody in patients with systemic lupus erythematosus were compared. For comparison, the values of antiprothrombin antibody and β2-glycoprotein I-dependent anticardiolipin antibody were also compared. a Antiprothrombin antibody and antiphosphatidylserine/prothrombin antibody. ρ = 0.514, P < 0.0001 by Spearman’s rank correlation. b Antiprothrombin antibody and β2 glycoprotein I-dependent anticardiolipin antibody. ρ = 0.086, P = 0.3103 by Spearman’s rank correlation. aPT-A, antiprothrombin antibody measured using high binding plates; aPS/PT, antiphosphatidylserine/prothrombin antibody; aβ2GPI/CL, β2 glycoprotein I-dependent anticardiolipin antibody