Metabolomic analysis for the unique profile and novel biomarkers of neuropsychiatric systemic lupus erythematosus

Abstract

Abstract Background: Neuropsychiatric systemic lupus erythematosus (NPSLE) is a common manifestation of systemic lupus erythematosus (SLE), with high mortality and disability rate. The lack of effective diagnostic methods, such as biomarkers, makes it difficult to diagnose and treat NPSLE. Metabolomics studies in autoimmune diseases shed new light on the identification of biomarkers beyond autoantibodies and cytokine profiling. This research aimed to explore the unique metabolomic profile, and discover novel molecular biomarkers and pathways for NPSLE. Methods: Cerebrospinal fluid samples from 26 NPSLE patients, 9 SLE controls, 7 connective tissue disease (CTD) controls and 9 nervous system disorder (NSD) controls were analysed to identify metabolomic signatures, significant pathways and biomarkers in the discovery cohort, using ultra performance liquid chromatography–tandem mass spectrometry (UPLC–MS). Next, the potential biomarkers were verified in an independent validation cohort including 22 NPSLE patients, 11 SLE controls and 4 NSD controls. Results: The metabolite profiles of cerebrospinal fluid (CSF) samples allowed significant differentiation of NPSLE patients from other disease controls. β-alanine metabolism and inositol phosphate metabolism pathways were significantly perturbed in NPSLE group. In the discovery cohort, 44 CSF metabolites with variable importance in projection (VIP) scores >1.5 and p < 0.05 were considered as the most differential metabolic biomarkers, including β-alanine amino acid and inositol. The diagnostic value of inositol was verified in the validation cohort, with the greatest specificity of 95.45% and the sensitivity of 60.00% for NPSLE. The CSF inositol level was higher in NPSLE patients with neuropsychiatric damage, cranial neuropathy and cerebrovascular disease. Conclusion: CSF metabolomic profile of NPSLE patients is unique from other disease controls. The pathway perturbations are involved in β-alanine metabolism and inositol phosphate metabolism. Inositol is a promising biomarker for the diagnosis and neuropsychiatric damage evaluation of NPSLE, and has potential relationships with specific NPSLE manifestations.