Serum metabolite differences detected by HILIC UHPLC-Q-TOF MS in systemic sclerosis

Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by extensive fibrosis and vascular damage. Vasculopathy, activation of the immune system, and diffuse fibrosis are all involved in the fatal pathogenesis of SSc. However, little metabolomic research has been conducted in SSc.This study included 30 SSc patients and 30 healthy individuals. The metabolite differences in serum samples were analyzed using ultra-high-pressure liquid chromatography and quadrupole-time-of-flight mass spectrometry. Meanwhile, serum metabolites were analyzed in patients with systemic involvement (lung or skin fibrosis).A total of 2360 ion peaks were detected, all of which were attributable to 38 metabolites. These metabolites primarily consisted of fatty acids, amino acids, and glycerophospholipids, which were the major metabolic pathways altered in SSc patients. Glutamine metabolism was the main pathway altered in SSc patients with lung involvement, whereas amino acid metabolism and steroid hormone biosynthesis were the main pathways altered in SSc patients with skin involvement.These findings suggested that metabolic profiles and pathways differed between SSc patients and healthy people, potentially providing new targets for SSc-directed therapeutics and diagnostics. Key Points • Metabolic profiles and pathways differed between SSc patients and healthy people. • The levels of trans-dehydroandrosterone are substantially lower in lcSSc than in dcSSc, potentially providing new targets for SSc patients with skin involvement. • L-glutamine could be used as a serum metabolic marker and a therapeutic target for SSc patients with lung involvement.