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In this pilot study, cerebrospinal fluid (CSF) was prospectively collected from 26 NMOSD patients in relapse and 16 controls with noninflammatory diseases and 6 neurometabolites in the tryptophan metabolic pathway, including 5\u2010hydroxytryptamine (5\u2010HT), kynurenine (KYN), melatonin (MLT), 5\u2010hydroxyindoleacetic acid (5HIAA), 3\u2010hydroxy\u2010o\u2010aminobenzoic acid (3\u2010HAA), and kynurenic acid (KYA), were measured by ultrahigh\u2010performance liquid chromatography\u2013tandem mass spectrometry (UHPLC\u2013MS\/MS). The association of Trp metabolites with NMOSD and its clinical parameters was evaluated. The role of KYN, which is a Trp metabolite involved in the binding of NMOSD\u2010IgG antibody to aquaporin 4 (AQP4), was also evaluated in vitro. CSF KYN was significantly decreased in patients with relapsing NMOSD compared to controls, and CSF KYN was associated with CSF white blood cells in NMOSD. In vitro experiments showed that NMOSD\u2010IgG specifically recognized KYN, which reversed the NMOSD\u2010IgG\u2010induced downregulation of AQP4 expression. Our results show that abnormal Trp metabolism occurs in NMOSD and that KYN might be a potential target for the treatment of AQP4\u2010IgG\u2010positive NMOSD patients.<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc15772-fig-0005-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p>","DOI":"10.1111\/jnc.15772","type":"journal-article","created":{"date-parts":[[2023,1,31]],"date-time":"2023-01-31T07:09:28Z","timestamp":1675148968000},"page":"259-267","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Decreased kynurenine in cerebrospinal fluid and potential role in neuromyelitis optica spectrum 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