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

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.