Lectin pathway proteins of the complement system in normotensive pregnancy and pre‐eclampsia

Abstract

Problem:The lectin pathway of the complement system may be involved in the pathogenesis of pre-eclampsia. We aimed to investigate changes in serum concentrations of a broad range of lectin pathway proteins during normal pregnancy and their association with pre-eclampsia, placental infarctions and intrauterine growth restriction (IUGR). Method of study:We included 51 women with normotensive pregnancies and 54 women with pregnancies complicated by pre-eclampsia. Blood samples were obtained at gestational weeks 16, 33, 37, and after delivery for the normotensive pregnant women and before and after delivery for women with pre-eclampsia. Mannose-binding lectin (MBL), H-and M-ficolin, collectin liver-1 (CL-L1), MBL-associated serine protease (MASP)-1, MASP-2 and MASP-3 and MBL-associated proteins of 19 (MAp19) and 44 (MAp44) kDa were analysed. Clinical information was obtained from medical records. The placentae were examined by two experienced perinatal pathologists.Results: Lectin pathway protein concentrations generally increased during normal pregnancy and decreased after delivery in both normotensive pregnant women and women with pre-eclampsia. Exceptions were MASP-3 which increased after delivery in both groups (P < 0.0001) and H-ficolin which increased after delivery in pre-eclampsia (P < 0.0001). H-ficolin (P < 0.0001), M-ficolin (P = 0.005) and MASP-3 (P = 0.03) concentrations were lower in women with pre-eclampsia than in normotensive pregnant women. Low MASP-3 concentrations were associated with placental infarction (P = 0.03) and IUGR (P = 0.04). Low H-ficolin concentrations were associated with IUGR (P < 0.01). Conclusion:In general, lectin pathway protein serum concentrations increased during normal pregnancy. H-ficolin and MASP-3 may be involved in the pathophysiology of pre-eclampsia and IUGR and could be potential future pre-eclampsia biomarkers. K E Y W O R D Scomplement pathway, ficolin, intrauterine growth restriction, mannose-binding lectin, mannose-binding protein-associated serine proteases, pre-eclampsia

Understanding and Preventing Placenta-Mediated Pregnancy Complications

“…[69][70][71] Recent evidence also suggests the role of complement dysregulation in the development of preeclampsia and fetal growth restriction through lectin pathway proteins. 72 Evidence from mouse models and human studies supports the role of complement activation in the pathogenesis of obstetrical APS. Mice deficient in the complement components (factor C3, C4, C5, and factor B) and mice treated with inhibitors of complement activation (anti-C5 antibody, C5a receptor antagonist peptide, and antifactor B antibody) are resistant to fetal loss induced by APLAs.…”

Remote ischemic preconditioning does not influence lectin pathway protein levels in head and neck cancer patients undergoing surgery

“…The concentrations of the LP proteins H-ficolin, M-ficolin, mannan-binding lectin (MBL), MBL-associated serine protease (MASP)-1, MASP-2, MASP-3, collectin liver-1, MBL-associated protein of 44 kilodalton (MAp44) and MAp19 were measured in EDTA plasma with time-resolved immunofluorometric assay (TRIFMA) at the Department of Biomedicine, Aarhus University, Denmark. Laboratory analyses were performed as described previously [33][34][35][36][37][38] with the exception of MASP-1 [39] and H-ficolin [40]. In brief, microtiter wells (FluoroNunc, Thermo Scientific™, Hvidovre, Denmark) were coated with specific antibodies or mannan for MBL and acetylated bovine serum albumin for H-ficolin assays.…”

“…Finally, an enhancement solution (Ampliqon, Odense, Denmark) was added and subsequently the plates were read by a fluorometer (Victor X5 1 , PerkinElmer). H-ficolin was analyzed using acetylated bovine serum albumin as the capturing agent as described in [40]. MASP-1 analysis was conducted as previously described [39] except that plates were coated with mouse anti-MASP-1 antibodies (clone 1H1G6, lot no A218033050, Genscript, Piscataway, NJ, USA) at 4 μg/ml final concentration in phosphate-buffered saline as described in [40].…”

Association of LEPTIN and other inflammatory markers with preeclampsia: A systematic review

“… Beneventi et al, 2020 investigated maternal and fetal plasma levels of leptin in pregnancies complicated by obesity and preeclampsia. The authors found that pregnant women with obesity had higher serum leptin levels than normal-weight subjects with and without hypertension or normotensive subjects with obesity ( Larsen et al, 2019 ; Beneventi et al, 2020 ; Abraham and Romani, 2022 ).…”

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Background: Preeclampsia is a serious pregnancy complication that affects 5%-10% of the obstetric population.Objective: To study inflammatory markers associated with preeclampsia.Search Strategy: Searches of articles on the topic published over a 10-year period (2009)(2010)(2011)(2012)(2013)(2014)(2015)(2016)(2017)(2018)(2019) were performed in three databases (PubMed, Cochrane, and Embase) using the keywords preeclampsia and inflammatory markers. The PubMed search using 10 years and humans as filters retrieved 124 articles.

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