Associations of neopterin and kynurenine-tryptophan ratio with survival in primary sclerosing cholangitis.

Biomarkers Cholangitis, Sclerosing Chromatography, Liquid Cross-Sectional Studies Humans Kynurenine Neopterin Tandem Mass Spectrometry Tryptophan
Biliary disease inflammation kynurenine neopterin sclerosis cholangitis tryptophan

Journal

Scandinavian journal of gastroenterology
ISSN: 1502-7708
Titre abrégé: Scand J Gastroenterol
Pays: England
ID NLM: 0060105

Informations de publication

Date de publication:
Apr 2021
Historique:
pubmed: 16 2 2021
medline: 19 8 2021
entrez: 15 2 2021
Statut: ppublish

Résumé

Biomarkers of inflammation may be of clinical utility in primary sclerosing cholangitis (PSC). We aimed to investigate the interferon gamma-related biomarkers neopterin and kynurenine-tryptophanratio (KT-ratio) in PSC. Circulating neopterin, tryptophan and kynurenine were measured with LC-MS/MS in multiple cross-sectional cohorts comprising in total of 524 PSC patients and 100 healthy controls from Norway, Germany and Sweden. Neopterin and KT-ratio were significantly increased in PSC patients compared with controls in both a discovery and a validation cohort from Norway. Furthermore, high neopterin and KT-ratio levels were associated with a shorter transplantation-free survival in the PSC patients in the Norwegian discovery cohort and the German validation cohort. However, in the validation PSC cohort from Sweden, no relationship between neopterin and KT-ratio and liver transplantation-free survival was observed. The correlations between neopterin and KT-ratio were moderate to strong and similar in all cohorts (rho 0.50-0.67). Neopterin and KT-ratio also correlated with C-reactive protein (rho 0.17-0.63) and revised Mayo risk score (rho 0.23-0.42) in all cohorts. Neopterin and KT-ratio were elevated in PSC and associated with liver transplantation-free survival in two independent PSC cohorts, highlighting a possible role of interferon gamma-driven inflammation in the pathogenesis. However, the lack of association with survival in one of the cohorts reduces the potential clinical value of neopterin and KT-ratioas biomarkers and highlights the need to validate new biomarkers in PSC in multiple cohorts.

Sections du résumé

BACKGROUND AND AIMS OBJECTIVE
Biomarkers of inflammation may be of clinical utility in primary sclerosing cholangitis (PSC). We aimed to investigate the interferon gamma-related biomarkers neopterin and kynurenine-tryptophanratio (KT-ratio) in PSC.
METHODS METHODS
Circulating neopterin, tryptophan and kynurenine were measured with LC-MS/MS in multiple cross-sectional cohorts comprising in total of 524 PSC patients and 100 healthy controls from Norway, Germany and Sweden.
RESULTS RESULTS
Neopterin and KT-ratio were significantly increased in PSC patients compared with controls in both a discovery and a validation cohort from Norway. Furthermore, high neopterin and KT-ratio levels were associated with a shorter transplantation-free survival in the PSC patients in the Norwegian discovery cohort and the German validation cohort. However, in the validation PSC cohort from Sweden, no relationship between neopterin and KT-ratio and liver transplantation-free survival was observed. The correlations between neopterin and KT-ratio were moderate to strong and similar in all cohorts (rho 0.50-0.67). Neopterin and KT-ratio also correlated with C-reactive protein (rho 0.17-0.63) and revised Mayo risk score (rho 0.23-0.42) in all cohorts.
CONCLUSIONS CONCLUSIONS
Neopterin and KT-ratio were elevated in PSC and associated with liver transplantation-free survival in two independent PSC cohorts, highlighting a possible role of interferon gamma-driven inflammation in the pathogenesis. However, the lack of association with survival in one of the cohorts reduces the potential clinical value of neopterin and KT-ratioas biomarkers and highlights the need to validate new biomarkers in PSC in multiple cohorts.

Identifiants

DOI: 10.1080/00365521.2021.1880627 PMID: 33583308
pubmed: 33583308
doi: 10.1080/00365521.2021.1880627
doi:

Substances chimiques

Biomarkers 0
Kynurenine 343-65-7
Neopterin 670-65-5
Tryptophan 8DUH1N11BX

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

443-452

Auteurs

Amandeep Kaur Dhillon (AK)

Norwegian PSC Research Center, Department of Transplantation Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway.
Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
Research Institute of Internal Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital Rikshospitalet, Oslo, Norway.

Christian Rupp (C)

Department of Internal Medicine IV, University Hospital of Heidelberg, Heidelberg, Germany.

Annika Bergquist (A)

Unit of Gastroenterology and Rheumatology, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.

Robert Voitl (R)

Department of Internal Medicine IV, University Hospital of Heidelberg, Heidelberg, Germany.

Trine Folseraas (T)

Norwegian PSC Research Center, Department of Transplantation Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway.
Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
Research Institute of Internal Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital Rikshospitalet, Oslo, Norway.
Section of Gastroenterology, Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway.

Marius Trøseid (M)

Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
Research Institute of Internal Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital Rikshospitalet, Oslo, Norway.
Section of Clinical Immunology and Infectious diseases, Oslo University Hospital Rikshospitalet, Oslo, Norway.

Øivind Midttun (Ø)

Bevital AS, Bergen, Norway.

Per M Ueland (PM)

Bevital AS, Bergen, Norway.
Laboratory of Clinical Chemistry, Haukeland University Hospital, Bergen, Norway.

Tom H Karlsen (TH)

Norwegian PSC Research Center, Department of Transplantation Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway.
Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
Research Institute of Internal Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital Rikshospitalet, Oslo, Norway.
Section of Gastroenterology, Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway.

Mette Vesterhus (M)

Norwegian PSC Research Center, Department of Transplantation Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway.
Department of Medicine, Haraldsplass Deaconess Hospital, Bergen, Norway.
Department of Clinical Science, University of Bergen, Bergen, Norway.

Martin Kummen (M)

Norwegian PSC Research Center, Department of Transplantation Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway.
Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
Research Institute of Internal Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital Rikshospitalet, Oslo, Norway.

Johannes R Hov (JR)

Norwegian PSC Research Center, Department of Transplantation Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway.
Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
Research Institute of Internal Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital Rikshospitalet, Oslo, Norway.
Section of Gastroenterology, Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway.
ORCID: 0000-0002-5900-8096

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Classifications MeSH

questionsmedicales.fr › Facteurs biologiques › Marqueurs biologiques › Associations of neopterin and...
questionsmedicales.fr › Maladies de l'appareil digestif › Maladie des voies biliaires › Maladies des canaux biliaires › Angiocholite › Angiocholite sclérosante › Associations of neopterin and...
questionsmedicales.fr › Techniques d'investigation › Techniques de chimie analytique › Chromatographie › Chromatographie en phase liquide › Associations of neopterin and...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études épidémiologiques › Études transversales › Associations of neopterin and...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Associations of neopterin and...
questionsmedicales.fr › Acides aminés, peptides et protéines › Acides aminés › Cynurénine › Associations of neopterin and...
questionsmedicales.fr › Enzymes et coenzymes › Coenzymes › Bioptérine › Néoptérine › Associations of neopterin and...
questionsmedicales.fr › Techniques d'investigation › Techniques de chimie analytique › Spectrométrie de masse › Spectrométrie de masse en tandem › Associations of neopterin and...
questionsmedicales.fr › Acides aminés, peptides et protéines › Acides aminés › Acides aminés essentiels › Tryptophane › Associations of neopterin and...