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Published on: October 12, 2017
Increased apolipoprotein-B:A1 ratio predicts cardiometabolic risk in patients with juvenile onset SLE
George A Robinson1, Kirsty E Waddington2, Leda Coelewij2
1Centre for Rheumatology Research, Department of Medicine, University College London, Rayne Building, London W1CE 6JF, UK; Centre for Adolescent Rheumatology Versus Arthritis, Department of Medicine, University College London, Rayne Building, London W1CE 6JF, UK.
Insights
High ApolipoproteinB:ApolipoproteinA1 ratio identifies juvenile-onset systemic lupus erythematosus (JSLE) patients at high cardiometabolic risk. This biomarker aids in stratifying JSLE patients for targeted interventions and improved outcomes.
Area of Science:
- Cardiovascular research
- Immunology
- Metabolomics
Background:
- Cardiovascular disease is a major cause of mortality in juvenile-onset systemic lupus erythematosus (JSLE).
- Traditional cardiovascular risk factors are less effective in predicting risk in younger patients.
- There is a need for reliable biomarkers to stratify JSLE patients and guide therapeutic strategies.
Purpose of the Study:
- To identify novel biomarkers for cardiovascular risk prediction in JSLE.
- To stratify JSLE patients based on their cardiometabolic risk profile.
- To explore the relationship between metabolic profiles, immune signatures, and clinical outcomes in JSLE.
Main Methods:
- Serum metabolomic analysis of over 200 lipoprotein measures in two JSLE cohorts.
- Analysis using hierarchical clustering, receiver operating characteristic analysis, and logistic regression.
- RNA-sequencing to assess gene expression in matched patient samples.
Main Results:
- Two distinct JSLE groups identified: one with an atherogenic and one with an atheroprotective lipoprotein profile.
- High ApolipoproteinB:ApolipoproteinA1 (ApoB:ApoA1) ratio distinguished these groups with high accuracy (96.2% specificity, 96.7% sensitivity).
- Elevated ApoB:ApoA1 ratio correlated with increased CD8+ T-cell frequencies, atherogenic gene expression, and worse clinical outcomes (SLE disease activity index).
Conclusions:
- High ApoB:ApoA1 ratio serves as a potential biomarker for increased cardiometabolic risk and adverse clinical outcomes in JSLE.
- This biomarker can assist in identifying JSLE patients needing intensified monitoring, lipid management, or lifestyle interventions.
- Multi-omic analysis provides a comprehensive understanding of cardiometabolic risk in JSLE.
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.
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