According to a recent study, complement activation is associated with an increased risk of pregnancy complications in patients with systemic lupus erythematosus (SLE) and antiphospholipid antibodies (APL) syndrome.
The study is part of PROMISSE (Predicators of pRegnacy Outcome: BioMarkers in antiphospholipid antibody Syndrome and System lupus Erythematosus) — a research effort to identify those lupus patients most at risk for pregnancy complications due to their disease and, by extension, those women who aren’t. It was presented during the 2015 American College of Rheumatology Annual Meeting, San Francisco.
Pregnancy in women with APL syndrome and/or SLE can present complications such as recurrent miscarriage, preeclampsia, placental insufficiency, and intrauterine growth restriction. Often, women with these conditions are advised not to get pregnant due to risk of poor pregnancy outcomes. However, only 20% of women who become pregnant when SLE is inactive indeed have poor pregnancy outcomes. Here, PROMISSE study researchers, led by Jane E. Salmon, MD, Director of the Lupus and APS Center of Excellence at Hospital for Special Surgery, set out to discover and identify biomarkers that could predict the probability of a successful or unsuccessful pregnancy.
The study has already yield results and identified some factors that point to future pregnancy complications, such as lupus anticoagulant and circulating anti-angiogenic factors. Recently, scientists identified that activation of complement, proteins that are part of the innate immune system with a series of biological functions that help body defenses, as a predictor of adverse pregnancies. In a study involving 497 SLE and/or APL patients and 207 controls, researchers observed that elevated levels of Bb and sC5b-9, two products of complement activation, were correlated with a 50% increase in the risk of pregnancy complications. In particular, levels of Bb were elevated at weeks 12 to 15 into pregnancy and until week 31 in women that eventually developed problems.
Identifying biomarkers that predict poor pregnancy outcomes allows clinicians to accurately counsel women who desire pregnancies. Furthermore, it allows for a risk-stratification of patients, leading to a more diligent monitorization of those at high risk of complicated pregnancies, along with the effective management of medical evaluation and costs.
In a press release, Dr. Salmon said of the positive outcomes that may result from this study: “In addition to recognizing those destined for adverse outcomes, our findings provide a rationale for blockade of complement, or its downstream mediators, to prevent pregnancy complications. We are in the final stages of embarking on a trial with an agent that blocks TNF-α, a mediator of placental injury produced as a consequence of complement activation. This will be the first trial of a biologic therapy to protect pregnancies at risk.”