TY  - JOUR
Y1  - 2023/12/04/
AV  - public
TI  - Systemic lupus erythematosus patients have unique changes in serum metabolic profiles across age associated with cardiometabolic risk
N1  - This work is licensed under a Creative Commons Attribution 4.0 International License. The images
or other third-party material in this article are included in the Creative Commons license,
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license, visit http://creativecommons.org/licenses/by/4.0/
UR  - http://dx.doi.org/10.1093/rheumatology/kead646
PB  - Oxford University Press (OUP)
ID  - discovery10184482
N2  - OBJECTIVES: Cardiovascular disease through accelerated atherosclerosis is a leading cause of mortality for patients with systemic lupus erythematosus (SLE), likely due to increased chronic inflammation and cardiometabolic defects over age. We investigated age-associated changes in metabolomic profiles of SLE patients and healthy controls (HCs). METHODS: Serum NMR metabolomic profiles from female SLE patients (n?=?164, age?=?14-76) and HCs (n?=?123, age?=?13-72) were assessed across age by linear regression and by age group between patients/HCs (Group-1, age???25, n?=?62/46; Group-2, age?=?26-49, n?=?50/46; Group-3, age???50, n?=?52/31) using multiple t-tests. The impact of inflammation, disease activity and treatments were assessed, and UK Biobank disease-wide association analysis of metabolites was performed. RESULTS: Age-specific metabolomic profiles were identified in SLE patients vs HCs, including reduced amino acids (Group-1), increased very-low-density lipoproteins (Group-2), and increased low-density lipoproteins (Group-3). Twenty-five metabolites were significantly altered in all SLE age groups, dominated by decreased atheroprotective high-density lipoprotein (HDL) subsets, HDL-bound apolipoprotein(Apo)A1 and increased glycoprotein acetyls (GlycA). Furthermore, ApoA1 and GlycA were differentially associated with disease activity and serological measures, as well as atherosclerosis incidence and myocardial infarction mortality risk through disease-wide association. Separately, glycolysis pathway metabolites (acetone/citrate/creatinine/glycerol/lactate/pyruvate) uniquely increased with age in SLE, significantly influenced by prednisolone (increased pyruvate/lactate) and hydroxychloroquine (decreased citrate/creatinine) treatment and associated with type-1 and type-2 diabetes by disease-wide association. CONCLUSIONS: Increasing HDL (ApoA1) levels through therapeutic/nutritional intervention, whilst maintaining low disease activity, in SLE patients from a young age could improve cardiometabolic disease outcomes. Biomarkers from the glycolytic pathway could indicate adverse metabolic effects of current therapies.
KW  - SLE
KW  -  age
KW  -  atherosclerosis
KW  -  cardiometabolic
KW  -  cardiovascular disease
KW  -  comorbidities
KW  -  lipids
KW  -  metabolism
KW  -  metabolomics
A1  - Jury, Elizabeth C
A1  - Peng, Junjie
A1  - Van Vijfeijken, Alexandra
A1  - Martin Gutierrez, Lucia
A1  - Woodridge, Laurel
A1  - Wincup, Chris
A1  - Pineda-Torra, Ines
A1  - Ciurtin, Coziana
A1  - Robinson, George A
JF  - Rheumatology
ER  -