[Untargeted metabolomics reveals differential serum metabolites and metabolic pathways in patients with primary Sjögren syndrome and thrombocytopenia].

OBJECTIVE: To systematically compare serum metabolome differences between patients with thrombocytopenia in primary Sjögren syndrome (pSS) and those with normal platelet count using non- targeted metabolomics technology, so as to identify differential metabolites, analyze the relationship between the relative quantification of these metabolites and platelet counts, and screen metabolic pathways associated with platelet counts in pSS patients with thrombocytopenia.

METHODS: The patients with pSS were selected and grouped according to the presence or absence of thrombocytopenia. Serum samples were collected from the study subjects and analyzed by liquid chromatography-mass spectrometry (LC-MS). The samples were analysed by human metabolome database (HMDB), lipid metabolites and pathways strategy (LIPID MAPS) and other databases for classification and annotation. The samples were analyzed by principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) for multi-variate statistical analysis to screen the differential metabolites between the groups, and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was made to study the functions and metabolic pathways of the metabolites. Correlation analysis was performed between the abundance of serum differential metabolites and platelet counts of pSS patients with thrombocytopenia.

RESULTS: This study included 62 patients with pSS, of whom 32 had thrombocytopenia and 30 had normal platelet counts. A total of 137 differentially expressed metabolites, enriched in 54 metabolic pathways, were found in the serum of patients with thrombocytopenia compared with those without thrombocytopenia. Among them, the expression of desoxycorticosterone, hydrocortisone, and taurine was positively correlated with platelet count, and the expression of neopterin was negatively correlated with platelet count. Enrichment analysis showed that desoxycorticosterone and hydrocortisone were enriched in the steroid hormone biosynthesis pathway, taurine was enriched in the metabolic pathway of taurine and taurine, and neopterin was enriched in the folate metabolic pathway.

CONCLUSION: Thrombocytopenia in pSS patients may be related to the reduced activity of steroid hormone biosynthesis pathway and the metabolic pathway of taurine and taurine, and the increased activity of the pathway of folate metabolism.