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Войти в исследования Lupus science & medicine · 2025
Proteomic analysis reveals angiogenesis-related plasma proteins associated with pre-eclampsia in SLE.
СтатьяМногоцентровое исследованиеПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Torell Agnes, Andersson Kerstin, Gunnarsson Iva, Svenungsson Elisabet, Zickert Agneta, Majczuk Sennström Maria, Trysberg Estelle, Bengtsson Anders A, Jönsen Andreas, Strevens Helena, Sjöwall Christopher, Saleh Muna, Pihl Sofia, Leonard Dag, Ronnblom Lars, Akhter Tansim, Bylund Johan, Jacobsson Bo, Rudin Anna, Stockfelt Marit, Lundell Anna-Carin
Аннотация
OBJECTIVE: Delivery of a small for gestational age (SGA) infant is a common pregnancy complication among women with SLE. Although disease activity and autoantibodies such as anti-Smith and anti-ribonucleoprotein associate with SGA, underlying pathological mechanisms remain unclear and reliable predictors are lacking. To address this, we applied a proteomic approach to identify proteins associated with SGA in SLE.
METHODS: Plasma samples were collected repeatedly during pregnancy, at delivery and from placental intervillous blood in women with SLE (n=83) and healthy controls (n=67) enrolled in the prospective SLE-Placenta study. Postpartum samples (≥6 months) from a subset of women with SLE (n=19) served as non-pregnant controls. Mass spectrometry was performed on a discovery cohort comprising six healthy uncomplicated pregnancies, eight uncomplicated SLE pregnancies and eight SLE pregnancies complicated by SGA (SLE-SGA). Differential protein abundance analysis was performed in R. Candidate proteins were quantified by ELISA in the full cohort.
RESULTS: Discovery proteomics identified four proteins with increased abundance in SLE-SGA compared with uncomplicated SLE pregnancies: endostatin (P adj =0.0003), angiogenin (P adj =0.03), insulin-like growth factor-binding protein 5 (P adj =0.03) and complement factor H-related protein 5 (P adj =0.004). In the full cohort, ELISA quantification did not confirm increased levels of these proteins in SLE-SGA but suggested elevated levels of the angiogenesis-related proteins endostatin and angiogenin in women with SLE who later developed pre-eclampsia. Endostatin levels were consistently higher in SLE compared with controls across all trimesters (p≤0.0001). Endostatin, but not angiogenin, was enriched in placental blood.
CONCLUSION: Our study did not validate the differentially abundant proteins as markers for SLE-SGA but suggested a link between the antiangiogenic and proangiogenic proteins, endostatin and angiogenin, respectively, and pre-eclampsia in SLE. Given the consistent elevation of endostatin throughout pregnancy in SLE compared with controls, its potential effects on placental development in SLE warrant further investigation.
METHODS: Plasma samples were collected repeatedly during pregnancy, at delivery and from placental intervillous blood in women with SLE (n=83) and healthy controls (n=67) enrolled in the prospective SLE-Placenta study. Postpartum samples (≥6 months) from a subset of women with SLE (n=19) served as non-pregnant controls. Mass spectrometry was performed on a discovery cohort comprising six healthy uncomplicated pregnancies, eight uncomplicated SLE pregnancies and eight SLE pregnancies complicated by SGA (SLE-SGA). Differential protein abundance analysis was performed in R. Candidate proteins were quantified by ELISA in the full cohort.
RESULTS: Discovery proteomics identified four proteins with increased abundance in SLE-SGA compared with uncomplicated SLE pregnancies: endostatin (P adj =0.0003), angiogenin (P adj =0.03), insulin-like growth factor-binding protein 5 (P adj =0.03) and complement factor H-related protein 5 (P adj =0.004). In the full cohort, ELISA quantification did not confirm increased levels of these proteins in SLE-SGA but suggested elevated levels of the angiogenesis-related proteins endostatin and angiogenin in women with SLE who later developed pre-eclampsia. Endostatin levels were consistently higher in SLE compared with controls across all trimesters (p≤0.0001). Endostatin, but not angiogenin, was enriched in placental blood.
CONCLUSION: Our study did not validate the differentially abundant proteins as markers for SLE-SGA but suggested a link between the antiangiogenic and proangiogenic proteins, endostatin and angiogenin, respectively, and pre-eclampsia in SLE. Given the consistent elevation of endostatin throughout pregnancy in SLE compared with controls, its potential effects on placental development in SLE warrant further investigation.