Kynurenine pathway activation and deviation to anthranilic and kynurenic acid in fibrosing chronic graft-versus-host disease.
Cell Rep Med
; 2(10): 100409, 2021 10 19.
Article
em En
| MEDLINE
| ID: mdl-34755129
ABSTRACT
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.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Riboflavina
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Vitamina B 6
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Transplante de Células-Tronco
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Doença Enxerto-Hospedeiro
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Ácido Cinurênico
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Cinurenina
Tipo de estudo:
Observational_studies
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Prognostic_studies
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Risk_factors_studies
Idioma:
En
Revista:
Cell Rep Med
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Itália