Rheumatology (Oxford). 2025 Apr 25:keaf158. doi: 10.1093/rheumatology/keaf158. Online ahead of print.
ABSTRACT
BACKGROUND: The aim was to investigate whether kynurenine pathway metabolites and neopterin increase probability for Sjögren’s disease (SjD) and their associations with clinical parameters and inflammatory biomarkers.
METHODS: In this case-control study, 97 SjD patients and 63 age- and sex-matched healthy volunteers were enrolled. Clinical and immunological characteristics, EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI) and the EULAR Sjögren’s Syndrome Patient-Report Index (ESSPRI) were evaluated. High-sensitivity C-reactive protein (hs-CRP); cysteine; leptin; resistin; adiponectin; interleukins, chemokines, and TNF receptors I and II were analyzed using a multiplex system. The concentrations of cystatin-C, neopterin, tryptophan, vitamin B6, and kynurenine metabolites were assessed using liquid chromatography-tandem mass spectrometry.
RESULTS: Tryptophan levels were lower in SjD (p= 0.012), and Kynurinine (p= 0.005), kynurenine/tryptophan ratio (KTR) (p= 0.001), and neopterin (p= 0.02) were higher. Kynurenine (OR 2.51, 95%CI 1.44-5.64), KTR (OR 3.45, 95% CI 1.76-6.74), neopterin (OR 4.28, 95% CI 1.95-9.42), and vitamin B6 metabolite (PAr) (OR 3.34, 95% CI 1.19-9.39) increased the chances for SjD. They were associated with disease activity, longer disease duration, depression, impaired salivary flow, hypergammaglobulinemia, neutropenia, hypocomplementemia, and positive anti-Ro/SSA and anti-La/SSB. Neopterin correlated with kynurenines, and both were also associated with PAr and pro-inflammatory cytokines, mainly TNF-α, IL-1β, and TNF receptors I and II.
CONCLUSION: Kynurenines and neopterin are interferon-gamma-inducible biomarkers associated with more chances for SjD and with disease activity, glandular dysfunction, autoantibodies, and immunological and inflammatory biomarkers.
PMID:40279290 | DOI:10.1093/rheumatology/keaf158
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