eprintid: 10184482
rev_number: 6
eprint_status: archive
userid: 699
dir: disk0/10/18/44/82
datestamp: 2024-01-02 12:26:53
lastmod: 2024-01-02 12:26:53
status_changed: 2024-01-02 12:26:53
type: article
metadata_visibility: show
sword_depositor: 699
creators_name: Jury, Elizabeth C
creators_name: Peng, Junjie
creators_name: Van Vijfeijken, Alexandra
creators_name: Martin Gutierrez, Lucia
creators_name: Woodridge, Laurel
creators_name: Wincup, Chris
creators_name: Pineda-Torra, Ines
creators_name: Ciurtin, Coziana
creators_name: Robinson, George A
title: Systemic lupus erythematosus patients have unique changes in serum metabolic profiles across age associated with cardiometabolic risk
ispublished: pub
divisions: UCL
divisions: B02
divisions: C10
divisions: D17
divisions: G90
keywords: SLE, age, atherosclerosis, cardiometabolic, cardiovascular disease, comorbidities, lipids, metabolism, metabolomics
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abstract: 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.
date: 2023-12-04
date_type: published
publisher: Oxford University Press (OUP)
official_url: http://dx.doi.org/10.1093/rheumatology/kead646
oa_status: green
full_text_type: pub
language: eng
primo: open
primo_central: open_green
verified: verified_manual
elements_id: 2114870
doi: 10.1093/rheumatology/kead646
medium: Print-Electronic
pii: 7458458
lyricists_name: Robinson, George
lyricists_name: Jury, Elizabeth
lyricists_name: Ciurtin, Coziana
lyricists_name: Wincup, Christopher
lyricists_name: Peng, Junjie
lyricists_id: GROBI58
lyricists_id: EJURY42
lyricists_id: CCIUR23
lyricists_id: CWINC43
lyricists_id: JPENG40
actors_name: Flynn, Bernadette
actors_id: BFFLY94
actors_role: owner
full_text_status: public
publication: Rheumatology
article_number: kead646
event_location: England
citation:        Jury, Elizabeth C;    Peng, Junjie;    Van Vijfeijken, Alexandra;    Martin Gutierrez, Lucia;    Woodridge, Laurel;    Wincup, Chris;    Pineda-Torra, Ines;         ... Robinson, George A; + view all <#>        Jury, Elizabeth C;  Peng, Junjie;  Van Vijfeijken, Alexandra;  Martin Gutierrez, Lucia;  Woodridge, Laurel;  Wincup, Chris;  Pineda-Torra, Ines;  Ciurtin, Coziana;  Robinson, George A;   - view fewer <#>    (2023)    Systemic lupus erythematosus patients have unique changes in serum metabolic profiles across age associated with cardiometabolic risk.                   Rheumatology      , Article kead646.  10.1093/rheumatology/kead646 <https://doi.org/10.1093/rheumatology%2Fkead646>.       Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/10184482/1/kead646.pdf