The Apolipoprotein-B to Apolipoprotein-A1 (ApoB:ApoA1) ratio may be an accurate biomarker capable of predicting increased cardiometabolic risk and worse clinical outcomes in patients with juvenile-onset systemic lupus erythematosus (JSLE), suggests a study published in EBioMedicine.
In this study, researchers collected peripheral blood samples from 31 patients with JSLE who comprised the discovery cohort and another 31 patients with JSLE who comprised the validation cohort. Researchers conducted serum metabolomic analysis with nuclear magnetic resonance spectroscopy on the samples. The analysis included greater than 200 lipoprotein measures.
The median age of each cohort was 19 years. Patients were stratified according to their disease activity, as measured by the SLE Disease Activity Index-2000 (SLEDAI-2000). Approximately 23% of patients in the discovery cohort and 3% of patients in the validation cohort had a SLEDAI-2000 greater than 4, indicating that these patients had higher disease activity at baseline. Comparatively, a SLEDAI-2000 score less than 4 is indicative of a milder disease compared.
Using the hierarchical clustering of the included lipoprotein measures, the investigators identified a group with an atherogenic metabolic profile and a group with an atheroprotective profile. The atherogenic group was characterized by reduced high-density lipoprotein (HDL), elevated very low-density lipoprotein (VLDL), intermediate density lipoprotein (IDL), and LDL particles. In contrast, the atheroprotective lipoprotein group was characterized by elevated HDL and reduced VLDL/IDL/LDL particles. A third group featured low serum HDL levels and low VLDL/LDL/IDL particles.
The ApoB:ApoA1 ratio differentiated the atherogenic and atheroprotective lipoprotein groups with 96.2% specificity and 96.7% sensitivity. Patients with JSLE who had a high ApoB:ApoA1 ratio had elevated CD8+ T-cell frequencies. Additionally, these patients featured a CD8+ T-cell transcriptomic profile that was enriched in genes correlated with atherogenic processes.
The ApoB:ApoA1 ratio at baseline was positively associated with the SLE disease activity index (r=0.43; P =.0009) and negatively associated with the Lupus Low Disease Activity State (r=-0.43; P =.0009) over a 5-year follow up. These findings suggest patients with JSLE and high ApoB:ApoA1 ratio may have a higher active disease trajectory over time.
A limitation of this study was the inclusion of patients with mostly low disease activity, which brings into question the generalizability of the findings across patients with greater active disease.
The investigators concluded that their findings propose a “high ApoB:ApoA1 ratio as a potential biomarker to stratify JSLE patients for a more personalized approach to lipid modification therapy.”
Robinson GA, Waddington KE, Coelewij L, et al. Increased apolipoprotein-B:A1 ratio predicts cardiometabolic risk in patients with juvenile onset SLE. EBioMedicine. 2021;65:103243. doi:10.1016/j.ebiom.2021.103243