Biomarcadores metabolômicos associados ao risco cardiovascular aumentado em pacientes com lúpus eritematoso sistêmico

Abstract

INTRODUCTION: Systemic Lupus Erythematosus (SLE) is a chronic, immune-mediated inflammatory disease in which altered immune regulation and the presence of autoantibodies result in the involvement of multiple organs. Furthermore, patients with SLE are at increased cardiovascular risk (CVR) and existing methods of screening for CVR are not sufficient. Metabolomics allows the detection and quantification of low molecular weight manifestations that occur in biological systems, which can become biomarkers of diseases. OBJECTIVES: To assess the metabolic profile that may be associated with increased RCV in this population. METHODS: Cross-sectional study of individuals with SLE aged 20 years or older at the Rheumatology service of the Professor Alberto Antunes University Hospital (Hupaa) – Federal University of Alagoas (Ufal). Controls were age-matched and had no autoimmune disease. the RCV by the modified Framingham score (x2). Metabolomic analysis of blood plasma was performed in patients and controls. The distinction of metabolites between groups was made by OPLS-DA (orthogonal least squares plot), and various permutations were defined as 2000 to evaluate the model. Important metabolites were selected by VIP threshold based on VIP plot (Importance plot variable) ≥ 1.5. The Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and the Systemic Lupus International Collaboration Clinics (SLICC) damage index were applied. RESULTS: The sample consisted of 79 SLE patients and 45 controls, where 21 SLE patients were classified as intermediate/high RCV. OPLS showed that SLE was discriminated from controls, with Q 2 0.778, R2Y 0.901 and p < 0.05, however OPLS does not discriminate patients with SLE and level/high CVR from patients with low CVR, with Q 2 - 0.00648 and p = 0.073, R2Y 0.266 and p = 0.055. Variable A VIP (important projection variable) found the metabolites glutathione, tyrosine, phenylalanine, alanine, methylhistidine, glutamine and histidine different between patients with SLE and controls, who demonstrated VIP ≥ 1.5. CONCLUSION: We found a discriminating metabolomic profile between SLE and control, however, we did not find it among patients with intermediate/high RCV and low RCV, probably due to the sample size. Metabolites may become biomarkers in the future, but more studies are needed to validate these findings due to multiple factors that may influence. Prospective studies would also be relevant to analyze the cardiovascular outcome.