Activity of the kynurenine pathway and its interplay with immunity in patients with pulmonary arterial hypertension

Heart
Malgorzata JasiewiczKarol Adam Kaminski

Abstract

We evaluated blood concentrations of kynurenine pathway metabolites, natural and induced regulatory T cells (nTreg, iTreg), and Th17 cells in order to examine the activity of the kynurenine pathway and its relation to immune status in patients with pulmonary arterial hypertension (PAH). Plasma concentrations of tryptophan, kynurenine, kynurenic acid, anthranilic acid, and 3-hydroxykynurenine were quantified in 26 patients with PAH (vs 30 healthy controls) at baseline and after 6 months, and assessed them in relation to clinical parameters, frequencies of lymphocyte subsets, and outcome. The PAH group presented higher concentrations of tryptophan (52.9 (IQR 46.3-57.5) vs 40.3 (35.2-46.3) µmol/L, p=0.00003), kynurenine 2.8 (2.4-3.4) vs 1.9 (1.5-2.3) µmol/L, p=0.000007), kynurenine/tryptophan ratio (0.051 (0.044-0.064) vs 0.043 (0.039-0.055), p=0.03), iTreg frequencies (10.5 (8.8-13.9)% vs 6.8 (5.2-9.5)%, p=0.002) and iTreg/Th17 (1.73 (1.2-2.8) vs 0.93 (0.61-1.27), p=0.003) together with lower ratios of kynurenic acid/kynurenine, 3-hydroxykynurenine/kynurenine, and anthranilic acid/kynurenine. Kynurenine concentrations and kynurenine/tryptophan ratio correlated positively with iTreg/Th17, and inversely with Th17 subsets, whereas k...Continue Reading

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Citations

Feb 7, 2017·Experimental Biology and Medicine·Jacek BartosiewiczDariusz Pawlak
Dec 28, 2017·The Journal of Biological Chemistry·Seung-Hyeon SeokYongna Xing
Mar 17, 2018·Circulation Research·Rasa TamosiunieneMark R Nicolls
Dec 4, 2019·British Journal of Pharmacology·Chunhua FuAndrew J Bryant
Aug 8, 2018·International Journal of Molecular Sciences·Andrew J BryantLyle L Moldawer
Jul 15, 2017·American Journal of Physiology. Lung Cellular and Molecular Physiology·Bence M NagyAndrea Olschewski

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