Anti-phosphatidylserine/prothrombin antibodies: an additional diagnostic marker for APS?

• DOI: 10.1007/s12026-013-8421-z
• Publication Date: 2013-04-09T12:02:26Z
• Authors: Francesca Pregnolato; Cecilia B. Chighi...; Susan Encabo; Zakera Shums; Gary L. Norman; Armando Tripodi; Veena Chantarangkul; Tiziana Bertero; Valeria De Micheli; Maria Orietta Borghi; Pier Luigi Meroni
• Keywords: Adult; Enzyme-Linked Immunosorbent Assay; Thrombosis; Phosphatidylserines; Middle Aged; Antiphospholipid Syndrome; Prognosis; Autoantigens; Sensitivity and Specificity; 3. Good health; Young Adult; 03 medical and health sciences; 0302 clinical medicine; Predictive Value of Tests; Lupus Coagulation Inhibitor; Humans; Prothrombin; Serologic Tests; Biomarkers; Aged

Among the diagnostic assays for anti-phospholipid syndrome (APS), lupus anticoagulant (LA) is the strongest predictor of thrombosis; however, it presents several limitations as interference with anticoagulant therapy and poor inter-laboratory agreement. Two-thirds of LA activity is apparently due to antibodies against prothrombin (PT), usually detectable by ELISA. Binding of PT to phosphatidylserine (PS) has been shown to enhance solid-phase anti-PT assay sensitivity. To determine the prevalence of antibodies against PS/PT (aPS/PT) in APS, we tested the semiquantitative QUANTA Lite(®) aPS/PT ELISA in a cohort of 80 APS patients. The prevalence of aPS/PT was 81.3%, rising to 87.6% when considering LA-positive subjects only. We observed a strong correlation between aPS/PT and LA (p = 0.006). To note, APS patients with thrombotic manifestations displayed significantly higher IgG aPS/PT titers compared to 20 aPL asymptomatic carriers (p = 0.012). To rule out a possible cross-reactivity of anti-β2 glycoprotein I antibodies (aβ2GPI) with PS/PT complex, we tested two monoclonal aβ2GPI antibodies and an affinity-purified (AP) polyclonal aβ2GPI IgG obtained from the serum of a patient reacting against both β2GPI and PS/PT. The two monoclonal antibodies did not show any reactivity against PS/PT complex, similarly the AP IgGs did not react toward PS/PT antigen while preserved their aβ2GPI activity. Our findings suggest that aPS/PT are a definite antibody population in APS. Moreover, the good correlation between aPS/PT ELISA and LA may support its use as a surrogate test for LA, particularly useful to overcome the technical limitations of the functional assay.