Detection of Antiphosphatidylserine/Prothrombin Antibodies and Their Potential Diagnostic Value

Abstract

Antiprothrombin antibodies, measured with phosphatidylserine/prothrombin complex (aPS/PT) ELISA, have been reported to be associated with antiphospholipid syndrome (APS). They are currently being evaluated as a potential classification criterion for this autoimmune disease, characterized by thromboses and obstetric complications. Given the present lack of clinically useful tests for the accurate diagnosis of APS, we aimed to evaluate in-house and commercial assays for determination of aPS/PT as a potential serological marker for APS. We screened 156 patients with systemic autoimmune diseases for antibodies against PS/PT, β 2-glycoprotein I, cardiolipin and for lupus anticoagulant activity. We demonstrated a high degree of concordance between the concentrations of aPS/PT measured with the in-house and commercial assays. Both assays performed comparably relating to the clinical manifestations of APS, such as arterial and venous thromboses and obstetric complications. IgG aPS/PT represented the strongest independent risk factor for the presence of obstetric complications, among all tested aPL. Both IgG and IgM aPS/PT were associated with venous thrombosis, but not with arterial thrombosis. Most importantly, the association between the presence of IgG/IgM aPS/PT and lupus anticoagulant activity was highly significant. Taken together, aPS/PT antibodies detected with the in-house or commercial ELISA represent a promising serological marker for APS and its subsets.

Evaluation of phosphatidylserine-dependent antiprothrombin antibody testing for the diagnosis of antiphospholipid syndrome: results of an international multicentre study

“…22,23 Many reports have shown the clinical utility of aPS/PT in the diagnosis of APS. 5,[24][25][26][27] In a large cohort of Japanese patients with systemic autoimmune diseases, the presence of aPS/PT significantly correlated with LA and with the clinical manifestations of APS. 5 Furthermore, aPS/PT appeared as the strongest independent risk factor for obstetric complications.…”

The Prevalence and Clinical Significance of Iga Anti-Phosphatidylserine/ Prothrombin Antibodies in Systemic Autoimmune Diseases

“…In the last decade, antibodies against prothrombin, specifically aPS/PT were recognized to be importantly associated with clinical manifestations of APS [20][21][22][23]28]. In our previous study we have reported that aPS/PT of IgG and IgM isotype are strongly associated with adverse pregnancy outcome, irrespective of other antiphospholipid antibodies [22], and that their detection is particularly important for evaluation of obstetric APS.…”

“…Although antiprothrombin antibodies have not yet been included in the classification criteria of APS, they are emerging as an increasingly important supportive marker [1,[19][20][21]. We have previously reported of IgG and/or IgM antibodies against complex phosphatidylserine/prothrombin (aPS/PT) exhibiting the highest percentage of LA activity, as compared to aCL or anti-β2GPI [19] and their strong association to thrombosis and adverse pregnancy outcome, irrespective of other antiphospholipid antibodies [20,22].…”

“…We have previously reported of IgG and/or IgM antibodies against complex phosphatidylserine/prothrombin (aPS/PT) exhibiting the highest percentage of LA activity, as compared to aCL or anti-β2GPI [19] and their strong association to thrombosis and adverse pregnancy outcome, irrespective of other antiphospholipid antibodies [20,22]. The latest systematic review concluded that routine measurement of aPS/PT antibodies of IgG and/or IgM isotype in serum or plasma might be useful in establishing the thrombotic risk of patients with previous thrombosis and/or (SLE) [21]. In addition a very recent international multicenter study advised measurement of IgG aPS/PT which might contribute to a better and more complete identification of patients with APS [23].…”

New Tests to Detect Antiphospholipid Antibodies: Antiprothrombin (aPT) and Anti-Phosphatidylserine/Prothrombin (aPS/PT) Antibodies

“…Early data from Atsumi et al showed that the presence of aPS/PT conferred an odds ratio for APS of 3.6 in his large cohort of 265 Japanese patients with systemic autoimmune diseases [10]. Recently, Zigon et al showed aPS/PT as the strongest independent risk factor for the presence of obstetric complications in a cohort of 156 patients with systemic autoimmune diseases [37]. Interestingly, while some studies support the association of aPS/PT with arterial thrombosis, mainly in the setting of ischemic/thrombotic cerebrovascular events [38,39] When systematically reviewing the topic [33••], we found 7 studies that directly compared aPT and aPS/PT and their OR for thrombosis in 1196 patients [5,9,[41][42][43][44].…”