Complement Pathway Activation Linked to Adverse Pregnancy Outcomes in Women With SLE

In women with systemic lupus erythematosus (SLE) or antiphospholipid (aPL) antibodies, complement pathway activation detectable early in pregnancy is associated with adverse pregnancy outcomes, according to the results of the PROMISSE study, published in the Annals of the Rheumatic Diseases.

A total of 487 pregnant women with SLE or aPL antibodies and 204 pregnant healthy control participants were enrolled in the PROMMISE (Predictors of pRegnancy Outcome: bioMarkers In antiphospholipid antibody Syndrome and Systemic Lupus Erythematosus) study. 

All participants entered the study at 12 weeks’ gestation and were assessed on a monthly basis. The adverse pregnancy outcomes were fetal death after 12 weeks’ gestation not explained by anatomic malformation, chromosomal abnormality, or congenital infection; neonatal death prior to hospital discharge because of complications associated with prematurity or placental insufficiency; preterm delivery at <36 weeks because of preeclampsia, placental insufficiency, or gestational diabetes; and small-for-gestational age neonate. 

Blood samples were obtained at each monthly visit to measure complement activation products, including Bb and sC5b-9.

Adverse pregnancy outcomes were reported in 20.5% of pregnancies in women with SLE or aPL antibodies. As early as 12 to 15 weeks’ gestation, levels of the complement activation products Bb and sC5b-9 were significantly higher among women with adverse pregnancy outcomes compared with women without an adverse pregnancy outcome, and these differences increased through 31 weeks. 

Additionally, Bb and sC5b-9 were significantly higher among women with SLE or aPL antibodies with no adverse pregnancy outcomes compared with pregnant control participants (P <.001).

Logistic regression analyses demonstrated that Bb and sC5b-9 at 12 to 15 weeks’ gestation remained significantly associated with adverse pregnancy outcomes (adjusted odds ratio [OR], 1.41 per standard deviation [SD] increase; 95% CI, 1.06-1.89; P =.019 and OR, 1.37 per SD increase; 95% CI, 1.05-1.80; P =.022, respectively) after controlling for demographic and clinical risk factors for adverse pregnancy outcomes. 

When the analyses were limited to patients with aPL antibodies only (n=161), the association between Bb and adverse pregnancy outcomes at 12 to 15 weeks was stronger (OR, 2.01 per SD increase; 95% CI, 1.16-3.49; P =.013).

The investigators concluded that increased Bb and sC5b-9 detected early in pregnancy are highly predictive of adverse pregnancy outcomes. These results support activation of complement, particularly the alternative pathway, as a contributor to adverse pregnancy outcomes among pregnant women with SLE or aPL antibodies.

Reference

Kim MY, Guerra MM, Kaplowitz E, et al.  Complement activation predicts adverse pregnancy outcome in patients with systemic lupus erythematosus and/or antiphospholipid antibodies [published online January 25, 2018]. Ann Rheum Dis. doi: 10.1136/annrheumdis-2017-212224