@article{177525cf67ec4336a3a1079bf48f17c4,
title = "Complement activation predicts adverse pregnancy outcome in patients with systemic lupus erythematosus and/or antiphospholipid antibodies",
abstract = "Objective Studies 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. Methods The 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. Results APO 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 (OR adj =1.41 per SD increase; 95% CI 1.06 to 1.89; P=0.019 and OR adj =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 (OR adj =2.01 per SD increase; 95% CI 1.16 to 3.49; P=0.013). Conclusion In 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.",
keywords = "antiphospholipid syndrome, complement, inflammation, pregnancy, systemic lupus erythematosus",
author = "Kim, {Mimi Y.} and Guerra, {Marta M.} and Elianna Kaplowitz and Laskin, {Carl A.} and Michelle Petri and Branch, {D. Ware} and Lockshin, {Michael D.} and Sammaritano, {Lisa R.} and Merrill, {Joan T.} and Porter, {T. Flint} and Allen Sawitzke and Lynch, {Anne M.} and Buyon, {Jill P.} and Salmon, {Jane E.}",
note = "Funding Information: 1Epidemiology and population Health, Albert Einstein College of Medicine, Bronx, new York, USA 2Medicine, Hospital for Special Surgery, new York, new York, USA 3Medicine, Mount Sinai Hospital and the University of toronto, toronto, ontario, Canada 4Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA 5obstetrics and Gynecology, University of Utah Health Sciences Center and Intermountain Healthcare, Salt Lake City, Utah, USA 6Medicine, Weill Cornell Medicine, new York, new York, USA 7Arthritis and Clinical Immunology program, oklahoma Medical research Foundation and the University of oklahoma Health Sciences Center, oklahoma City, oklahoma, USA 8Medicine, University of Utah Health Sciences Center, Salt Lake City, Utah, USA 9ophthalmology, University of Colorado School of Medicine, Aurora, Colorado, USA 10Medicine, new York University School of Medicine, new York, new York, USA Acknowledgements We are grateful to Mary S Stephenson, Alan peaceman and Munther Khamashta for contributing patients to the study. We thank Quidel Corporation for their guidance with the complement split product measurements and S Ananth Karumanchi for thoughtful discussions about angiogenic factors. Funding Information: Funding research reported in this publication was supported by the national Institute of Arthritis and Musculoskeletal and Skin diseases of the national Institutes of Health under Award number ro1 Ar49772 (proMISSE Study, MYK, MMG, EK, CAL, Mp, dWB, MdL, LrS, JtM, tFp, AS, JpB, JES), Mary Kirkland Center for Lupus research (JES, MdL) and nIH Ar43727, Ar69572 (Mp). Publisher Copyright: {\textcopyright} Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved.",
year = "2018",
month = apr,
doi = "10.1136/annrheumdis-2017-212224",
language = "English (US)",
volume = "77",
pages = "549--555",
journal = "Annals of the Rheumatic Diseases",
issn = "0003-4967",
publisher = "BMJ Publishing Group",
number = "4",
}