AB0552 ELEVATED KYNURENINE LEVELS IN PATIENTS WITH PRIMARY SJÖGREN’S SYNDROME

Abstract

BackgroundSjögren’s syndrome (SS) is a chronic autoimmune systemic inflammatory disease of unknown origin that predominantly affects the exocrine glands (mainly salivary and lacrimal glands). Primary Sjögren’s syndrome (pSS) is a disease whose etiology is not yet fully understood, as in most autoimmune diseases, where genetic, epigenetic and environmental factors are hypothesized to play to the pathogenesis of the disease. Metabolism of tryptophan (Trp) via the kynurenine (Kyn) pathway has been proposed to act a substantial role in inflammatory processes.ObjectivesIn the present study, we investigated levels of Trp and its metabolites in the Kyn pathway in patients with pSS and in healthy controls. Also, the relationship between Trp metabolites and laboratory parameters, disease activity was evaluated in patients with pSS.MethodsThe study included 34 pSS patients and 42 healthy individuals, and serum Trp and Kyn concentrations were measured by liquid chromatography with tandem mass spectrometry (LC-MS/MS). Trp degradation was predicted using the ratio of Kyn and Trp concentrations (Kyn/Trp). The EULAR Sjögren’s syndrome disease activity index (ESSDAI) and the EULAR Sjögren’s Syndrome Patient Reported Index (ESSPRI) were used to evaluate pSS activity.ResultsIn our study, the mean serum Trp concentration was found to be considerably lower in the pSS group compared to the control group (p= 0.001). The levels of Kyn (p= 0.019) and Kyn/Trp ratio (p <0.001) were significantly higher in the pSS group compared to the control group (Table 1). Trp concentration was negatively correlated with physician global assessment (r=-0.568, p<0.001), positively correlated with albumin (r=0.384, p=0.025) and hemoglobin (p=0.396, r=0.020). The Kyn/Trp ratio was negatively correlated with CRP (r=-0.369, p=0.032). There was no correlation between the Trp pathway and disease activity parameters ESSDAI and ESRPI.Table 1.Comparison of the kynurenine pathway results of patients with Sjögren’s syndrome and the controlsSjögren’s syndrome (n=34) median (IQR)Control(n=42) median (IQR)pKynurenine (ng/ml)485 (378-601)386 (356-496)0.019Tryptophan (ng/ml)10660 (9160- 12282)12258 (11442-14711)0.001Kynurenine/tryptophan ratio (%)4 (3-6)3 (3-4)<0.001*Mann-Whitney U testConclusionIn conclusion, we found that kynurenine pathway metabolism was altered in patients with pSS. This suggests that tryptophan metabolism may be closely linked to the disease pathogenesis of pSS.References[1]Stefanski A-L, Tomiak C, Pleyer U, Dietrich T, Burmester GR, Dörner T. The diagnosis and treatment of Sjögren’s syndrome. Deutsches Ärzteblatt International. 2017;114(20):354.[2]Maldini C, Seror R, Fain O, Dhote R, Amoura Z, De Bandt M, et al. Epidemiology of primary Sjögren’s syndrome in a French multiracial/multiethnic area. Arthritis care & research. 2014;66(3):454-63.[3]Moffett JR, Namboodiri MA. Tryptophan and the immune response. Immunology and cell biology. 2003;81(4):247-65.[4]Schroecksnadel K, Winkler C, Duftner C, Wirleitner B, Schirmer M, Fuchs D. Tryptophan degradation increases with stage in patients with rheumatoid arthritis. Clinical rheumatology. 2006;25(3):334-7.Disclosure of InterestsNone declared