Positivity of antiphosphatidylserine/prothrombin antibodies identifies a subgroup of more severe antiphospholipid syndrome patients.

Abstract

Objectives: Antiphospholipid syndrome (APS) is an autoimmune disease combining the occurrence of thrombotic and/or obstetric events with the persistent presence of antiphospholipid antibodies (i.e. lupus anticoagulant (LA), anti-cardiolipin (aCL) and anti-beta-2-glycoprotein I (aβ2GPI) antibodies). Among the autoantibodies regularly found in patients with APS, antiphosphatidylserine/prothrombin (anti-PS/PT) antibodies seem promising because of their high correlation with LA positivity. The main objective of this study was to characterise the population of anti-PS/PT and/or anti-PT-antibody-positive patients in terms of APS severity and organ damage.

Methods: We performed a prospective, monocentric, descriptive study of patients who had a dosage of IgG and IgG anti-PS/PT between March 2019 and May 2020. Clinical and biological data were collected from 148 patients, 128 had thrombosis including 64 with known APS according to the Sydney criteria, and 20 patients with antiphospholipid-antibody positivity (mainly LA positivity) without clinical manifestation of APS. Cases with active neoplasia including myeloproliferative disorders at the time of inclusion were excluded.

Results: Anti-PS/PT positive patients did not display any particular thrombotic phenotype but had significantly more renal impairment (renal failure p=0.01 and proteinuria p=0.04), migraine (p=0.03), and thrombocytopenia (p=0.001) than negative patients, notably in the associated-APS patient group. Moreover, tetra-positivity (LA+, aCL+, a2βGPI+, and anti-PS/PT+) was associated with more severe APS (thrombotic recurrences, thrombosis under anticoagulant treatment, and a trend of more frequent catastrophic antiphospholipid syndrome). To a lesser extent, a similar phenotype was observed with anti-PT antibody positivity, but the 58.7% agreement with anti-PS/PT antibodies, suggests the presence of common but also specific PS/PT epitopes.

Conclusions: The increased thrombotic risk associated with the aPS/PT antibodies would justify their testing in all APS patients in complementarity with the conventional anti-phospholipid antibodies to propose the best-adjusted treatment.