The Role of Anti‐Phosphatidylserine/Prothrombin Antibodies and the Lectin Complement Pathway in Anti‐Phospholipid Antibody‐Associated Preterm Delivery

OBJECTIVE: Antiphospholipid antibodies (aPL) may directly affect placentation and trigger local complement-mediated inflammation/thrombosis. Obstetric complications in the antiphospholipid syndrome (APS) are still frequent despite therapy/close monitoring, and the identification of new risk biomarkers is an unmet need. We aimed to prospectively investigate the prognostic value of classification/non-classification laboratory APS criteria and markers of complement activation for pregnancy complications, in particular preterm delivery (PTD). METHODS: We followed 60 women prospectively during pregnancy and postpartum: 33 aPL-positive (20 APS and 13 aPL-carriers) and 27 aPL-negative [5 systemic lupus erythematosus (SLE), 11 rheumatoid arthritis (RA) and 11 undifferentiated connective tissue diseases (UCTD)]. aPL criteria tests, anti-phosphatidylserine/prothrombin (anti-PS/PT) IgG/IgM and anti-β2glycoprotein I-Domain I (anti-β2GPI-DI) IgG, complement products (C3, C4, C3a, C5a, sC5b-9, MBL) and complement pathway activity [Classical (CP), Alternative (AP), and Lectin (LP)] were measured in 231 available specimens. RESULTS: PTD was experienced in 21% of aPL-positive and 15% of aPL-negative women. Anti-PS/PT IgG/IgM titers were significantly higher in PTD vs. non-PTD women (p<0.05) at almost all time-points. At variance with CP and AP, LP activity in aPL-positive PTD was lower than in non-PTD, reaching a statistically significant difference compared with aPL-negative PTD patients (p<0.05). Moreover, LP activity significantly correlated with anti-PS/PT IgG/IgM titers, both measured in the first trimester (p<0.05), and all of them significantly correlated with the week of gestation at delivery (p<0.05). CONCLUSIONS: The reduced LP activity and the higher anti-PS/PT IgG/IgM titers in PTD aPL-positive women during the first trimester suggest their use as early prognostic tools for PTD in aPL-positive pregnant women.