The findings were discussed in an oral presentation titled, “Metabolomics in juvenile-onset SLE: identifying new biomarkers to predict cardiovascular risk,” (abstract #OP0148) at the 2019 Annual European Congress of Rheumatology (EULAR), recently held in Madrid.
SLE, the most prevalent form of lupus, is a chronic autoimmune disease characterized by tissue inflammation, rash, pain, fatigue, depression, and impaired cognition. JSLE is more severe than the adult-onset form of the disorder. Patients with JSLE have an increased risk of developing heart disease, among the major causes of death in these patients.
In patients with adult-onset SLE, alterations in the immune system have been linked to perturbations in lipid (fat molecules) metabolism. However, in patients with JSLE, little is known about the impact of lipid metabolism on the development and progression of the disease.
In this study, a group of researchers from the University College of London (UCL) set out to determine whether abnormalities in lipid metabolism could be linked to a higher risk of heart disease among patients with JSLE using in-depth metabolomics (the study of metabolism and all its key players).
The study involved two groups of JSLE patients — an initial discovery group of 35 patients and a second confirmatory group of 31 patients — as well as one group of 39 age- and sex-matched healthy individuals (controls).
Using unbiased hierarchical clustering, investigators divided patients with a similar lipoprotein profile, immune cell characteristics, and clinical features into three groups:
- Group 1: Decreased high-density lipoproteins (HDL) and increased very low and low-density lipoproteins (VLDL/LDL); high immune system overactivation; high disease activity;
- Group 2: High HDL and low VLDL/LDL; low immune system overactivation; low disease activity;
- Group 3: Intermediate levels of HDL, VLDL, and LDL; high immune system overactivation.
Based on these observations, they hypothesized that patients from group 1 would be at higher risk of developing heart disease, followed by those from group 3, and finally those from group 2.
To confirm their hypothesis, they used a series of classical heart disease biomarkers, including the atherogenic index of plasma and the apolipoprotein B/apolipoprotein A1 (ApoB:A1) ratio, and found their initial assumptions were correct.
Moreover, they discovered that ApoB:A1 was the best biomarker to distinguish patients at high risk of heart disease (group 1), from those at low risk (group 2). In addition, they found this ApoB:A1 ratio biomarker remained stable over long periods of time.
“Our study identifies ApoB:A1 ratio and metabolomic lipoprotein signatures as potential new biomarkers to predict [heart disease] risk in patients with juvenile-onset SLE,” George Robinson, senior research associate at the Centre for Adolescent Rheumatology Versus Arthritis, UCL, said in a news release.
“Patient stratification using these biomarkers could provide an opportunity for tailored disease treatments using lipid modification therapy and lifestyle interventions,” he said.
Remarkably, they found the same pattern of metabolic stratification in the second group of 31 JSLE patients, further validating this form of risk assessment.
“Regular assessment for traditional and disease-related risk factors for cardiovascular disease is very important in patients with SLE,” said Tanita Wilhelmer, chair of Europe’s Young PARE group, which advocates for patients ages 18–35 with rheumatic diseases. “We welcome these data to support the identification of those at greatest risk.”