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

• Published in: Annals of the rheumatic diseases Vol. 77; no. 4; pp. 549 - 555
• Main Authors: Kim, Mimi Y, Guerra, Marta M, Kaplowitz, Elianna, Laskin, Carl A, Petri, Michelle, Branch, D Ware, Lockshin, Michael D, Sammaritano, Lisa R, Merrill, Joan T, Porter, T Flint, Sawitzke, Allen, Lynch, Anne M, Buyon, Jill P, Salmon, Jane E
• Format: Journal Article
• Language: English
• Published: England Elsevier Limited 01.04.2018
• Subjects: 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; antiphospholipid syndrome; systemic lupus erythematosus; complement; inflammation; pregnancy
• ISSN: 0003-4967; 1468-2060; 1468-2060
• DOI: 10.1136/annrheumdis-2017-212224

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.