Antiphospholipid antibody carriers and patients with quiescent antiphospholipid syndrome show persistent subclinical complement activation

Objectives Complement activation has been advocated as one mechanism by which aPLs can induce thrombosis. In patients with catastrophic APS or re-thrombosis, enhanced complement activation has been shown, even in the quiescent phase of the disease. We aimed to assess complement activation and to investigate its association with clinical variables in aPL-positive patients with a favourable disease course.Methods Subjects with at least two consecutive positive aPL results obtained >= 12 weeks apart were enrolled. They were subjects without a history of thrombosis or pregnancy morbidity (aPL carriers), patients with pregnancy morbidity alone, i.e. obstetric APS patients (OAPS patients), and/or patients with arterial, venous, or small-vessel thrombotic APS (TAPS patients); for enrolment, all patients were required to have been free of symptoms for >= 2 years. Patients affected with systemic autoimmune diseases were excluded. Healthy age- and sex-matched subjects were included as controls. Plasma C5a and C5b-9 levels were assessed by commercially available ELISA assays. The non-parametric Mann-Whitney test and Spearman's correlation were applied.Results Thirty-seven OAPS patients, 38 TAPS patients, 42 aPL carriers and 30 healthy subjects were enrolled. The median C5a and C5b-9 levels were significantly higher in quiescent aPL-positive patients (OAPS, TAPS, aPL carriers) compared with controls: C5a ng/ml 10.61 [interquartile range (IQR) 6.87-15.46] vs 4.06 (2.66-7.35), P < 0.001; C5b-9 ng/ml 283.95 (175.8-439.40) vs 165.90 (124.23-236.8), P < 0.001. Similar C5a and C5b-9 levels were observed in OAPS and TAPS patients and aPL carriers. A positive correlation between the median C5b-9 levels and the number of aPL-positive tests was found (P = 0.002).Conclusion The persistence of aPL antibodies is associated with a persistent subclinical activation of the complement cascade.