Kynurenines and neopterin are interferon-gamma-inducible biomarkers for Sjögren's disease

Abstract

Objectives: 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.

Keywords: PAr index; Sjögren’s disease; biomarkers; interferon-gamma; kynurenine pathway; neopterine.