Complement activation in the plasma and placentas of women with different subsets of antiphospholipid syndrome

Abstract

ProblemAs antiphospholipid antibody‐positive women with adverse pregnancy outcomes have higher plasma complement activation product levels, and the placentas of women with antiphospholipid syndrome (APS) exhibit C4d complement component deposition, complement activation involvement has been hypothesized in APS pregnancy complications.Method of studyPlasma levels of C5a and C5b‐9 complement components of 43 APS non‐pregnant patients and 17 pregnant APS women were measured using enzyme‐linked immunosorbent assay. The results were compared with those of 16 healthy non‐pregnant women and eight healthy pregnant women, respectively. Placenta samples of five APS patients at high risk of pregnancy complications and of five healthy controls were subjected to immunoblotting analysis with specific antibodies to C5b‐9 and CD46, CD55, CD59 complement regulators.ResultsThe mean plasma C5a and C5b‐9 levels were significantly higher in the non‐pregnant APS patients with previous thrombosis ± pregnancy morbidity (P = .0001 and P = .0034, respectively) and in the pregnant APS women with adverse outcomes (P = .0093 for both). Similarly, C5b‐9 amounts were significantly higher in the adverse pregnancy outcome placenta (P = .0115) than in those associated to a favorable outcome. The mean CD46, CD55 and CD59 amounts were, instead, lower, although not always significantly, in the placentas of all the high‐risk APS women with respect to the control placentas.ConclusionData analysis demonstrated that there was significant complement activation in the more severe subset of APS patients and in only the adverse pregnancy outcome APS women. Further studies will clarify whether the lower CD46, CD55, and CD59 expressions in the APS placentas are limited to only high‐risk APS patients.

Clinical characteristics, inflammation and coagulation status in patients with immunological disease-related chronic cerebrospinal venous insufficiency

“…Apart from having elevated autoimmune antibodies, they were also correlated with decreased C3 or C4 and increased ESR or IgG. These results were consistent with former clinical studies (19)(20)(21). Moreover, groups with APS and IgG4-RD presented in a relatively younger population than that with SS and had a higher CRP level than that with decreased C3.…”

The Complement System in the Pathophysiology of Pregnancy and in Systemic Autoimmune Rheumatic Diseases During Pregnancy

“…Blood samples from 161 aPL positive women including 60 with SLE were analyzed for the presence of Bb and SC5b-9 and increased levels of both activation products were found in all patients with adverse obstetric outcome (53). This finding has been confirmed by a more recent study, reporting higher C5a and C5b-9 levels in APS pregnant patients with pregnancy complications compared to healthy pregnant women (54). More convincing evidence supporting the role of C in inducing aPLdependent placental damage and pregnancy failure has been obtained from the immunohistochemical analysis of placental tissue for C deposits.…”

“…Two groups have documented deposits of C5b-9 mainly localized on extravillous trophoblasts of placentae from aPL-positive women and observed no difference in the staining intensity between APS and control groups (56,57). These findings are in contrast with the data obtained by Scambi et al who reported higher levels of C5b-9 solubilized from APS placentae compared to controls, in particular in APS patients who experienced a pregnancy complication (54). Our group has conducted a prospective study on 13 APS patients with medium to high titers of anti-β2GPI antibodies and positive LA who had pregnancies that resulted in one abortion, four fetal losses, and eight preterm deliveries (58).…”

Anti‐phospholipid antibodies and reproductive failures

“…Reggia et al did not find evident correlation with pregnancy outcomes, despite the fact pregnant APS women presented significantly lower C3 and C4 compared to healthy pregnant controls 65 . When complement products were assessed, plasma levels of C5b‐9 and Bb were associated with adverse pregnancy outcomes in APS pregnancies 66,67 . C5‐blocking monoclonal antibody, eculizumab, was effective in treating severe forms of thrombotic APS 68 .…”