On the correlation of tryptophan and its kynurenine pathway metabolites level in blood, saliva and urine in systemic sclerosis patients.

Abstract

Systemic sclerosis (SSc) is a progressive autoimmune connective tissue disease, leading to disability and often to a shorter life expectancy. Numerous reports indicate that the kynurenine pathway (KP) is dysregulated in systemic sclerosis (SSc). Therefore, this exploratory pilot study aimed to assess whether levels of tryptophan (TRP) and its selected metabolites within the KP correlate across different body fluids. Forty-one patients with SSc participated in the study. Blood, saliva, and morning urine samples were collected. The concentrations of TRP, kynurenine (KYN), 3-hydroxykynurenine (3-HK), quinolinic acid (QUIN), and kynurenic acid (KYNA) were measured. In addition, precursor/product ratios reflecting the activity of KP enzymes were calculated. In the cohort of patients comprising both men and women the significant correlations were observed between blood plasma and urine levels of KYN (ρ = 0.531, P < 0.001), as well as between the KYN/TRP (ρ = 0.774, P < 0.001), 3-HK/TRP (ρ = 0.549, P = 0.001), QUIN/TRP (ρ = 0.467, P = 0.002), and KYNA/TRP (ρ = 0.412, P < 0.008) ratios in patients with SSc. Correlation between plasma and saliva was limited to KYNA in female SSc (ρ = 0.526, P < 0.007) which suggests that saliva has limited diagnostic value for assessing KP activity in patients with SSc. In contrast, urine-based measurements were promising and support further development of diagnostic approaches based on urinary KP metabolites.