{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T10:38:52Z","timestamp":1790678332832,"version":"4.1.0"},"reference-count":29,"publisher":"BMJ","issue":"3","content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["Heart"],"accepted":{"date-parts":[[2015,11,23]]},"published-print":{"date-parts":[[2016,2,1]]},"abstract":"<jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>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).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>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\u2005months, and assessed them in relation to clinical parameters, frequencies of lymphocyte subsets, and outcome.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>The PAH group presented higher concentrations of tryptophan (52.9 (IQR 46.3\u201357.5) vs 40.3 (35.2\u201346.3) \u00b5mol\/L, p=0.00003), kynurenine 2.8 (2.4\u22123.4) vs 1.9 (1.5\u20132.3) \u00b5mol\/L, p=0.000007), kynurenine\/tryptophan ratio (0.051 (0.044\u20130.064) vs 0.043 (0.039\u20130.055), p=0.03), iTreg frequencies (10.5 (8.8\u201313.9)% vs 6.8 (5.2\u20139.5)%, p=0.002) and iTreg\/Th17 (1.73 (1.2\u20132.8) vs 0.93 (0.61\u20131.27), 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 kynurenic acid\/kynurenine and anthranilic acid\/kynurenine ratios correlated positively with Th17. Adverse outcomes occurred in 9 of 26 patients and they showed higher baseline concentrations of kynurenine (3.6 (2.8\u20134.3) vs 2.7 (2.1\u20133.2) \u00b5mol\/L, p=0.033). Median kynurenine values \u22653.4\u2005\u00b5mol\/L (67% sensitivity, 94% specificity) identified patients with a worse clinical course.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>PAH is characterised by upregulated tryptophan metabolism and enhanced biosynthesis of kynurenine. Elevated kynurenine concentration is associated with an adverse clinical course. Dysregulated immunity, delineated by Treg-Th17 imbalance, is directly related to diverse activation of the kynurenine pathway, indicating the potential interplay between kynurenines and the immune system in PAH.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/heartjnl-2015-308581","type":"journal-article","created":{"date-parts":[[2016,1,14]],"date-time":"2016-01-14T16:53:10Z","timestamp":1452790390000},"page":"230-237","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":42,"title":["Activity of the kynurenine pathway and its interplay with immunity in patients with pulmonary arterial hypertension"],"prefix":"10.1136","volume":"102","author":[{"given":"Malgorzata","family":"Jasiewicz","sequence":"first","affiliation":[{"name":"Department of Cardiology, Medical University of Bialystok, Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcin","family":"Moniuszko","sequence":"additional","affiliation":[{"name":"Department of Regenerative Medicine and Immune Regulation, Medical University of Bialystok, Bialystok, Poland"},{"name":"Department of Allergology and Internal Medicine, Medical University of Bialystok, Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dariusz","family":"Pawlak","sequence":"additional","affiliation":[{"name":"Department of Pharmacodynamics, Medical University of Bialystok, Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malgorzata","family":"Knapp","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Medical University of Bialystok, Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malgorzata","family":"Rusak","sequence":"additional","affiliation":[{"name":"Department of Haematological Diagnostics, Medical University of Bialystok, Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Remigiusz","family":"Kazimierczyk","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Medical University of Bialystok, Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wlodzimierz Jerzy","family":"Musial","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Medical University of Bialystok, Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milena","family":"Dabrowska","sequence":"additional","affiliation":[{"name":"Department of Haematological Diagnostics, Medical University of Bialystok, Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9465-2581","authenticated-orcid":false,"given":"Karol Adam","family":"Kaminski","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Medical 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