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Increased apolipoprotein-B:A1 ratio predicts cardiometabolic risk in patients with juvenile onset SLE

Robinson, GA; Waddington, KE; Coelewij, L; Peng, J; Naja, M; Wincup, C; Radziszewska, A; ... Jury, EC; + view all (2021) Increased apolipoprotein-B:A1 ratio predicts cardiometabolic risk in patients with juvenile onset SLE. EBioMedicine , Article 103243. 10.1016/j.ebiom.2021.103243. (In press). Green open access

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Abstract

Background: Cardiovascular disease is a leading cause of mortality in patients with juvenile-onset systemic lupus erythematosus (JSLE). Traditional factors for cardiovascular risk (CVR) prediction are less robust in younger patients. More reliable CVR biomarkers are needed for JSLE patient stratification and to identify therapeutic approaches to reduce cardiovascular morbidity and mortality in JSLE. Methods: Serum metabolomic analysis (including >200 lipoprotein measures) was performed on a discovery (n=31, median age 19) and validation (n=31, median age 19) cohort of JSLE patients. Data was analysed using cluster, receiver operating characteristic analysis and logistic regression. RNA-sequencing assessed gene expression in matched patient samples. Findings: Hierarchical clustering of lipoprotein measures identified and validated two unique JSLE groups. Group-1 had an atherogenic and Group-2 had an atheroprotective lipoprotien profile. Apolipoprotein(Apo)B:ApoA1 distinguished the two groups with high specificity (96.2%) and sensitivity (96.7%). JSLE patients with high ApoB:ApoA1 ratio had increased CD8+ T-cell frequencies and a CD8+ T-cell transcriptomic profile enriched in genes associated with atherogenic processes including interferon signaling. These metabolic and immune signatures overlapped statistically significantly with lipid biomarkers associated with sub-clinical atherosclerosis in adult SLE patients and with genes overexpressed in T-cells from human atherosclerotic plaque respectively. Finally, baseline ApoB:ApoA1 ratio correlated positively with SLE disease activity index (r=0.43, p=0.0009) and negatively with Lupus Low Disease Activity State (r=-0.43, p=0.0009) over 5-year follow-up. Interpretation: Multi-omic analysis identified high ApoB:ApoA1 as a potential biomarker of increased cardiometabolic risk and worse clinical outcomes in JSLE. ApoB:ApoA1 could help identify patients that require increased disease monitoring, lipid modification or lifestyle changes. Funding: Lupus UK, The Rosetrees Trust, British Heart Foundation, UCL & Birkbeck MRC Doctoral Training Programme and Versus Arthritis.

Type: Article
Title: Increased apolipoprotein-B:A1 ratio predicts cardiometabolic risk in patients with juvenile onset SLE
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.ebiom.2021.103243
Publisher version: http://dx.doi.org/10.1016/j.ebiom.2021.103243
Language: English
Additional information: © 2021 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)
Keywords: Juvenile-onset systemic lupus erythematosus, Cardiovascular disease, Lipids, CD8+ T cells, Interferon
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Experimental and Translational Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inflammation
URI: https://discovery.ucl.ac.uk/id/eprint/10122923
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