title: Anti-phosphatidylserine/prothrombin antibodies: an additional diagnostic marker for APS?
abstract: 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.
authors.affiliation: Immunology Research Laboratory, IRCCS Istituto Auxologico Italiano, Via Zucchi 18, 20095, Cusano Milanino, Milan, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Pregnolato
authors.forename: Cecilia B
authors.initials: CB
authors.lastname: Chighizola
authors.forename: Susan
authors.initials: S
authors.lastname: Encabo
authors.forename: Zakera
authors.initials: Z
authors.lastname: Shums
authors.forename: Gary L
authors.initials: GL
authors.lastname: Norman
authors.forename: Armando
authors.initials: A
authors.lastname: Tripodi
authors.forename: Veena
authors.initials: V
authors.lastname: Chantarangkul
authors.forename: Tiziana
authors.initials: T
authors.lastname: Bertero
authors.forename: Valeria
authors.initials: V
authors.lastname: De Micheli
authors.forename: Maria Orietta
authors.initials: MO
authors.lastname: Borghi
authors.forename: Pier Luigi
authors.initials: PL
authors.lastname: Meroni
mesh_terms: D000328:Adult; D000368:Aged; D016736:Antiphospholipid Syndrome / Q000175:diagnosis* / Q000276:immunology; D001324:Autoantigens / Q000276:immunology*; D015415:Biomarkers / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D016682:Lupus Coagulation Inhibitor / Q000097:blood; D008875:Middle Aged; D010718:Phosphatidylserines / Q000276:immunology; D011237:Predictive Value of Tests; D011379:Prognosis; D011516:Prothrombin / Q000276:immunology*; D012680:Sensitivity and Specificity; D012698:Serologic Tests / Q000379:methods*; D013927:Thrombosis / Q000175:diagnosis* / Q000276:immunology; D055815:Young Adult
chemical_list: D001324:Autoantigens; D015415:Biomarkers; D016682:Lupus Coagulation Inhibitor; D010718:Phosphatidylserines; D011516:Prothrombin