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

Mimi Kim, Marta M. Guerra, Elianna Kaplowitz, Carl A. Laskin, Michelle Petri, D. Ware Branch, Michael D. Lockshin, Lisa R. Sammaritano, Joan T. Merrill, T. Flint Porter, Allen Sawitzke, Anne M. Lynch, Jill P. Buyon, Jane E. Salmon

Research output: Contribution to journalArticle

22 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)549-555
Number of pages7
JournalAnnals of the Rheumatic Diseases
Volume77
Issue number4
DOIs
StatePublished - Apr 1 2018

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Antiphospholipid Antibodies
Complement Activation
Pregnancy Outcome
Systemic Lupus Erythematosus
Chemical activation
Pregnancy
Logistics
Blood
Placental Insufficiency
Alternative Complement Pathway
Fetal Death
Pre-Eclampsia
Pregnant Women
Logistic Models
Regression Analysis
Demography

Keywords

  • antiphospholipid syndrome
  • complement
  • inflammation
  • pregnancy
  • systemic lupus erythematosus

ASJC Scopus subject areas

  • Rheumatology
  • Immunology and Allergy
  • Immunology
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Complement activation predicts adverse pregnancy outcome in patients with systemic lupus erythematosus and/or antiphospholipid antibodies. / Kim, Mimi; 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.

In: Annals of the Rheumatic Diseases, Vol. 77, No. 4, 01.04.2018, p. 549-555.

Research output: Contribution to journalArticle

Kim, M, Guerra, MM, Kaplowitz, E, Laskin, CA, Petri, M, Branch, DW, Lockshin, MD, Sammaritano, LR, Merrill, JT, Porter, TF, Sawitzke, A, Lynch, AM, Buyon, JP & Salmon, JE 2018, 'Complement activation predicts adverse pregnancy outcome in patients with systemic lupus erythematosus and/or antiphospholipid antibodies', Annals of the Rheumatic Diseases, vol. 77, no. 4, pp. 549-555. https://doi.org/10.1136/annrheumdis-2017-212224
Kim, Mimi ; 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. / Complement activation predicts adverse pregnancy outcome in patients with systemic lupus erythematosus and/or antiphospholipid antibodies. In: Annals of the Rheumatic Diseases. 2018 ; Vol. 77, No. 4. pp. 549-555.
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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.",
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T1 - Complement activation predicts adverse pregnancy outcome in patients with systemic lupus erythematosus and/or antiphospholipid antibodies

AU - Kim, Mimi

AU - Guerra, Marta M.

AU - Kaplowitz, Elianna

AU - Laskin, Carl A.

AU - Petri, Michelle

AU - Branch, D. Ware

AU - Lockshin, Michael D.

AU - Sammaritano, Lisa R.

AU - Merrill, Joan T.

AU - Porter, T. Flint

AU - Sawitzke, Allen

AU - Lynch, Anne M.

AU - Buyon, Jill P.

AU - Salmon, Jane E.

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N2 - 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.

AB - 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.

KW - antiphospholipid syndrome

KW - complement

KW - inflammation

KW - pregnancy

KW - systemic lupus erythematosus

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