Kynurenine pathway activation and deviation to anthranilic and kynurenic acid in fibrosing chronic graft-versus-host disease.
Adolescent
Adult
Aged
Chemokine CXCL9
/ blood
Female
Fibrosis
Gene Expression Regulation
Graft vs Host Disease
/ blood
Humans
Indoleamine-Pyrrole 2,3,-Dioxygenase
/ blood
Interleukin-18
/ blood
Kynurenic Acid
/ blood
Kynurenine
/ blood
Kynurenine 3-Monooxygenase
/ blood
Leukemia
/ genetics
Lymphoma
/ genetics
Male
Metabolic Networks and Pathways
/ genetics
Middle Aged
Retrospective Studies
Riboflavin
/ blood
Severity of Illness Index
Signal Transduction
Stem Cell Transplantation
Transplantation, Homologous
Tryptophan
/ blood
Vitamin B 6
/ blood
ortho-Aminobenzoates
/ blood
CXCL9
IL-18
anthranilic acid
fibrosing chronic graft-versus-host disease
indoleamine-2,3-dioxygenase
kynurenic acid
kynurenine
tryptophan
vitamin B2
vitamin B6
Journal
Cell reports. Medicine
ISSN: 2666-3791
Titre abrégé: Cell Rep Med
Pays: United States
ID NLM: 101766894
Informations de publication
Date de publication:
19 10 2021
19 10 2021
Historique:
received:
23
06
2020
revised:
27
10
2020
accepted:
20
09
2021
entrez:
10
11
2021
pubmed:
11
11
2021
medline:
11
11
2021
Statut:
epublish
Résumé
Fibrosing chronic graft-versus-host disease (cGVHD) is a debilitating complication of allogeneic stem cell transplantation (alloSCT). A driver of fibrosis is the kynurenine (Kyn) pathway, and Kyn metabolism patterns and cytokines may influence cGVHD severity and manifestation (fibrosing versus gastrointestinal [GI] cGVHD). Using a liquid chromatography-tandem mass spectrometry approach on sera obtained from 425 patients with allografts, we identified high CXCL9, high indoleamine-2,3-dioxygenase (IDO) activity, and an activated Kyn pathway as common characteristics in all cGVHD subtypes. Specific Kyn metabolism patterns could be identified for non-severe cGVHD, severe GI cGVHD, and fibrosing cGVHD, respectively. Specifically, fibrosing cGVHD was associated with a distinct pathway shift toward anthranilic and kynurenic acid, correlating with reduced activity of the vitamin-B2-dependent kynurenine monooxygenase, low vitamin B6, and increased interleukin-18. The Kyn metabolite signature is a candidate biomarker for severe fibrosing cGVHD and provides a rationale for translational trials on prophylactic vitamin B2/B6 supplementation for cGVHD prevention.
Identifiants
pubmed: 34755129
doi: 10.1016/j.xcrm.2021.100409
pii: S2666-3791(21)00267-6
pmc: PMC8561165
doi:
Substances chimiques
CXCL9 protein, human
0
Chemokine CXCL9
0
IDO1 protein, human
0
IL18 protein, human
0
Indoleamine-Pyrrole 2,3,-Dioxygenase
0
Interleukin-18
0
ortho-Aminobenzoates
0
anthranilic acid
0YS975XI6W
Kynurenine
343-65-7
Vitamin B 6
8059-24-3
Tryptophan
8DUH1N11BX
Kynurenine 3-Monooxygenase
EC 1.14.13.9
Kynurenic Acid
H030S2S85J
Riboflavin
TLM2976OFR
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Pagination
100409Informations de copyright
© 2021 The Authors.
Déclaration de conflit d'intérêts
The authors declare no competing interests.
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