Abstract
Objectives Complement activation has been advocated as one of the possible mechanisms by which antiphospholipid antibodies (aPLs) can induce thrombosis. Our aim was to assess complement activation in patients with antiphospholipid antibody syndrome with pregnancy morbidity alone (OAPS) at the time of pregnancy and in a quiescent phase of the disease, and to compare it with healthy controls.
Methods Consecutive patients fulfilling the Sydney criteria for OAPS, and healthy non-pregnant age- and sex-matched subjects were enrolled. Patients with other systemic autoimmune diseases were excluded. Two samples in OAPS patients, one during the first trimester of pregnancy and one at least 2 years after delivery, were collected. Plasma C5a and C5b-9 levels were assessed by commercially available ELISA assays. Non-parametric Mann-Whitney test and Spearman’s rank coefficient were applied.
Results Thirty-seven OAPS patients and 23 healthy subjects were enrolled. Median C5a and C5b-9 levels were significantly higher in OAPS patients than in controls, both during pregnancy and in the subsequent phase of quiescent disease (figure 1): pregnant samples (available in 17 patients) vs. healthy controls C5a ng/ml 10.84 (IQR 4.59–14.12) vs. 3.93 (3.04–5.85), p=0.003; C5b-9 ng/ml 216.9 (137.0–367.7) vs. 165.4 (117.5–197.3), p=0.05; non-pregnant samples C5a ng/ml 11.4 (IQR 7.6–14.3), p<0.001; C5b-9 ng/ml 243.4 (175.7–391.6), p=0.001. Similar C5a and C5b-9 serum levels were observed in pregnant vs. quiescent OAPS (C5a p=0.47, and C5b-9 p=0.61, respectively).
Conclusions A persistent activation of the complement cascade characterized patients with APS with pregnancy comorbidity. In this predisposing milieu, pregnancy represent the ‘second hit’ that can trigger aPL-mediated thrombosis and placental inflammation.
C5a and C5b-9 plasma levels in healthy subjects and patients with obstetric APS in pregnancy and in a quiescent phase of the disease
