Nuclear magnetic resonance-based metabolomics reveals similar metabolomics profiles in undifferentiated peripheral spondyloarthritis and reactive arthritis.

INTRODUCTION: After exclusion of reactive, psoriatic and enteritis-associated arthritis, a group of "undifferentiated" peripheral spondyloarthritis (pSpA) remains. This group shares genetics, T-cell repertoire, and cytokines with reactive arthritis (ReA). ReA is preceded by gut or urogenital infection. Otherwise the two may be similar. We know little of the metabolic pathways driving undifferentiated pSpA or ReA. Nuclear magnetic resonance (NMR)-based metabolomics presents a hypothesis-free approach to study and compare metabolic pathways driving undifferentiated pSpA and ReA.

METHODS: Serum and synovial fluid metabolomes of 19 ReA and 13 undifferentiated pSpA, and serum metabolome of 18 controls were profiled using 1 H-based NMR. Partial least square-discriminant analysis (PLS-DA) identified metabolites different in patients as compared to controls. Multivariate analysis confirmed these. Altered metabolic pathways were identified using metabolites set enrichment analysis (MSEA). The serum and synovial fluid metabolomes of ReA and undifferentiated pSpA were compared.

RESULTS: Ten serum metabolites of ReA/undifferentiated pSpA were different from those of controls. Six metabolites were different between serum and synovial fluid of these patients. MSEA identified five pathways different between patients and controls, and five pathways different between serum and synovial fluid of patients. PLS-DA showed no difference between the metabolomes of serum or of synovial fluid between ReA and undifferentiated pSpA.

DISCUSSION: Identified metabolic pathways may be explored further to understand the pathogenesis and to target therapeutics. The similar immuno-metabolic pathways suggest similar pathogenesis of ReA and undifferentiated pSpA. Thus, they should be studied as a single disease entity.