Highlights from

EULAR 2019

European Congress of Rheumatology

Madrid 12-15 June 2019

New biomarkers for cardiovascular risk in juvenile-onset systemic lupus erythematosus

"Our study identifies ApoB:A1 ratio and metabolomic lipoprotein signatures as potential biomarkers to predict cardiovascular risk in patients with juvenile-onset systemic lupus erythematosus (JSLE)," said Dr George Robinson (University College London, United Kingdom). "Patient stratification using these biomarkers could provide an opportunity for tailored disease treatments using lipid modification therapy and lifestyle interventions."

JSLE is an autoimmune disorder, featured by immune dysregulation, chronic inflammation and increased cardiovascular risk. Cardiovascular disease is the leading cause of mortality in JSLE. The findings of Robinson et al. in adult-onset SLE link immune cell dysregulation with dyslipidaemia. However, little is known about the immune profile or whether abnormal lipid metabolism contributes to disease pathogenesis in JSLE.

In-depth metabolomics was used to investigate dyslipidaemia and cardiovascular risk in JSLE patients. The goal was to relate this to clinical and immune cell profiles and to identify biomarkers to predict cardiovascular risk in these patients. The study included a discovery cohort of 35 JSLE patients and 39 age/sex-matched healthy donors. Metabolic biomarker analysis using NMR and in-depth immune cell phenotyping by flow cytometry were performed on the serum and peripheral blood mononuclear cells taken from the subjects. Data were analysed using cluster and correlation-correlation and ROC analysis. The metabolomic patient stratification was validated in the second cohort of 31 JSLE patients.

Patient stratification by metabolomic profile revealed 3 groups with a unique lipoprotein profile, immune cell phenotype, and clinical presentation. The patients in Group 1 were identified as high cardiovascular risk due to their lipoprotein profile (decreased high- density lipoproteins (HDL) and increased very low and low-density lipoproteins (VLDL/LDL)). Group 1 had a significant increase in plasmablasts and activated T cells compared to matched healthy controls and had clinical features linked to increased disease activity. These immunopathogenic properties were not seen in the low cardiovascular risk Group 2, which also had the opposite lipoprotein profile (increased HDL and decreased VLDL/LDL). Group 3 had an intermediate cardiovascular risk but a pro-inflammatory immune cell profile.

A highly predictive biomarker to distinguish between JSLE patients in Group 1 and 2, indicating high and low cardiovascular risk respectively, was the ApoB:A1 ratio (ROC area under the curve>0.99). Longitudinal analysis revealed that the ApoB:A1 ratio remained stable over time.

  1. Robinson G, et al. Abstract OP0148. EULAR 2019

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