Journal Article

Complement activation predicts adverse pregnancy outcome in patients with systemic lupus erythematosus and/or antiphospholipid antibodies

Guerra, Marta M, Sawitzke, Allen, Petri, Michelle, Lockshin, Michael D, Buyon, Jill P, Porter, T Flint, Kim, Mimi Y, Sammaritano, Lisa R, Merrill, Joan T, Branch, D Ware, Lynch, Anne M, Kaplowitz, Elianna, Laskin, Carl A, Salmon, Jane E

2018

Overview

ObjectiveStudies in mouse models implicate complement activation as a causative factor in adverse pregnancy outcomes (APOs). We investigated whether activation of complement early in pregnancy predicts APOs in women with systemic lupus erythematosus (SLE) and/or antiphospholipid (aPL) antibodies.MethodsThe PROMISSE Study enrolled pregnant women with SLE and/or aPL antibodies (n=487) and pregnant healthy controls (n=204) at <12 weeks gestation and evaluated them monthly. APOs were: fetal/neonatal death, preterm delivery <36 weeks because of placental insufficiency or preeclampsia and/or growth restriction <5th percentile. Complement activation products were measured on serial blood samples obtained at each monthly visit.ResultsAPO occurred in 20.5% of SLE and/or aPL pregnancies. As early as 12–15 weeks, levels of Bb and sC5b-9 were significantly higher in patients with APOs and remained elevated through 31 weeks compared with those with normal outcomes. Moreover, Bb and sC5b-9 were significantly higher in patients with SLE and/or aPL without APOs compared with healthy controls. In logistic regression analyses, Bb and sC5b-9 at 12–15 weeks remained significantly associated with APO (ORadj=1.41 per SD increase; 95% CI 1.06 to 1.89; P=0.019 and ORadj=1.37 per SD increase; 95% CI 1.05 to 1.80; P=0.022, respectively) after controlling for demographic and clinical risk factors for APOs in PROMISSE. When analyses were restricted to patients with aPL (n=161), associations between Bb at 12–15 weeks and APOs became stronger (ORadj=2.01 per SD increase; 95% CI 1.16 to 3.49; P=0.013).ConclusionIn pregnant patients with SLE and/or aPL, increased Bb and sC5b-9 detectable early in pregnancy are strongly predictive of APOs and support activation of complement, particularly the alternative pathway, as a contributor to APOs.

• Publisher: Elsevier Limited
• Subject: Adult / Alternative pathway / Animal models / Antibodies, Antiphospholipid - immunology / Antiphospholipid antibodies / Arthritis / Autoimmune diseases / Case-Control Studies / Complement activation / Complement Activation - immunology / Complement Factor B - analysis / Complement Factor B - immunology / Complement Membrane Attack Complex - analysis / Complement Membrane Attack Complex - immunology / Ethnicity / Female / Fetuses / Gestation / Humans / Immunoglobulins / Kinases / Laboratories / Lupus / Lupus Erythematosus, Systemic - immunology / Neonates / Placenta / Pre-eclampsia / Preeclampsia / Pregnancy / Pregnancy complications / Pregnancy Complications - immunology / Pregnancy Outcome / Risk factors / Studies / Systemic lupus erythematosus / Thrombosis / Womens health