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Multicenter Study
. 2018 Apr;77(4):549-555.
doi: 10.1136/annrheumdis-2017-212224. Epub 2018 Jan 25.

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

Mimi Y Kim  1 , Marta M Guerra  2 , Elianna Kaplowitz  2 , Carl A Laskin  3 , Michelle Petri  4 , D Ware Branch  5 , Michael D Lockshin  2   6 , Lisa R Sammaritano  2   6 , Joan T Merrill  7 , T Flint Porter  5 , Allen Sawitzke  8 , Anne M Lynch  9 , Jill P Buyon  10 , Jane E Salmon  2   6
Affiliations
Multicenter Study

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

Mimi Y Kim et al. Ann Rheum Dis. 2018 Apr.

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 (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).

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.

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Conflict of interest statement

Competing interests: DWB reports serving on the UCB Pharmaceuticals Advisory Board; JES has received an investigator-initiated grant from UCB Pharmaceuticals and consulting fees from Alnylam and Alexion.

Figures

Figure 1
Figure 1
(A) Levels of Bb and (B) levels of sC5b-9 during pregnancy for patients with SLE and/or aPL with and without APO and healthy control women (no SLE, no APL) without APO. Values represent means and standard errors. Sample size is the number of specimens available from individual patients from each group at each time point. P-values by two sample t-tests: SLE and/or aPL with APO vs. SLE and/or aPL with no APO: * = <0.05, **= <0.01, *** = <0.0001; SLE and/or aPL with no APO vs Healthy Control: § = <0.0001
Figure 1
Figure 1
(A) Levels of Bb and (B) levels of sC5b-9 during pregnancy for patients with SLE and/or aPL with and without APO and healthy control women (no SLE, no APL) without APO. Values represent means and standard errors. Sample size is the number of specimens available from individual patients from each group at each time point. P-values by two sample t-tests: SLE and/or aPL with APO vs. SLE and/or aPL with no APO: * = <0.05, **= <0.01, *** = <0.0001; SLE and/or aPL with no APO vs Healthy Control: § = <0.0001
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