Kynurenine pathway can be a potential biomarker of fatigue in primary Sjögren’s syndrome

Objective Primary Sjögren’s syndrome (pSS) is a chronic autoimmune disease with low quality of life caused by various constitutional symptoms and glandular dysfunction. Although fatigue is one of the most frequent symptoms in pSS, its aetiology or biomarkers are poorly elucidated. We investigated potential relationship between severity of fatigue and the kynurenine pathway in pSS. Methods Clinical data and blood samples of 81 patients were obtained from a prospective cohort for pSS and compared with age- and sex-matched healthy controls (HC). Severity of fatigue was defined according to the fatigue domain scores in the ESSPRI. Potential biomarkers related to the kynurenine pathway were determined using ELISA. Results Of the total, 44 patients were defined as the “severe fatigue (ESSPRI fatigue ≥ 5)” group, whereas 37 as the “less fatigue (ESSPRI fatigue <5)”. Serum tryptophan levels in the severe fatigue group were significantly lower while those of kynurenine were higher than in the others. Serum interferon gamma, IDO1, and quinolinic acid levels were mostly higher in the less fatigue group. Kynurenine/tryptophan ratios were distinctly higher in the severe fatigue group than both HC and the less fatigue group (p<0.001). This ratio showed a strong degree of positive correlation (r=0.624, p <0.001) with severity of fatigue in pSS while the other markers showed fair degrees of correlation. Conclusion Serum markers related to the kynurenine pathway, especially the kynurenine/tryptophan ratio, may be associated with severity of fatigue in pSS. These results can provide guidance for further investigations on fatigue in pSS.