Proteomic analysis reveals angiogenesis-related plasma proteins associated with pre-eclampsia in SLE
(2025) In Lupus Science and Medicine 12(2).- Abstract
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... (More)
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.
(Less)
- author
- organization
- publishing date
- 2025-12-07
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Autoimmune Diseases, Lupus Erythematosus, Systemic, Risk Factors
- in
- Lupus Science and Medicine
- volume
- 12
- issue
- 2
- article number
- e001819
- publisher
- BMJ Publishing Group
- external identifiers
-
- pmid:41360610
- scopus:105024672036
- ISSN
- 2053-8790
- DOI
- 10.1136/lupus-2025-001819
- language
- English
- LU publication?
- yes
- additional info
- Publisher Copyright: © Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.
- id
- 6feff91c-dafb-4ceb-84ba-cc3d4988eea1
- date added to LUP
- 2026-02-11 16:53:56
- date last changed
- 2026-07-03 16:38:18
@article{6feff91c-dafb-4ceb-84ba-cc3d4988eea1,
abstract = {{<p>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 <sub>adj</sub>=0.0003), angiogenin (P <sub>adj</sub>=0.03), insulin-like growth factor-binding protein 5 (P <sub>adj</sub>=0.03) and complement factor H-related protein 5 (P <sub>adj</sub>=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.</p>}},
author = {{Torell, Agnes and Andersson, Kerstin and Gunnarsson, Iva and Svenungsson, Elisabet and Zickert, Agneta and Majczuk Sennström, Maria and Trysberg, Estelle and Bengtsson, Anders A. and Jönsen, Andreas and Strevens, Helena and Sjöwall, Christopher and Saleh, Muna and Pihl, Sofia and Leonard, Dag and Ronnblom, Lars and Akhter, Tansim and Bylund, Johan and Jacobsson, Bo and Rudin, Anna and Stockfelt, Marit and Lundell, Anna Carin}},
issn = {{2053-8790}},
keywords = {{Autoimmune Diseases; Lupus Erythematosus, Systemic; Risk Factors}},
language = {{eng}},
month = {{12}},
number = {{2}},
publisher = {{BMJ Publishing Group}},
series = {{Lupus Science and Medicine}},
title = {{Proteomic analysis reveals angiogenesis-related plasma proteins associated with pre-eclampsia in SLE}},
url = {{http://dx.doi.org/10.1136/lupus-2025-001819}},
doi = {{10.1136/lupus-2025-001819}},
volume = {{12}},
year = {{2025}},
}