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

Abstract

BACKGROUND AND AIMS:

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:

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:

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:

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.

• Authors: Amandeep Kaur Dhillon, Christian Rupp, Annika Bergquist, Robert Voitl, Trine Folseraas, Marius Trøseid, Øivind Midttun, Per M Ueland, Tom H Karlsen, Mette Vesterhus, Martin Kummen, Johannes R Hov
• Journal: Scandinavian journal of gastroenterology (Scand J Gastroenterol) Vol. 56 Issue 4 Pg. 443-452 (Apr 2021) ISSN: 1502-7708 [Electronic] England
• PMID: 33583308 (Publication Type: Journal Article)

Chemical References

• Biomarkers
• Kynurenine
• Neopterin
• Tryptophan

Topics

• Biomarkers
• Cholangitis, Sclerosing
• Chromatography, Liquid
• Cross-Sectional Studies
• Humans
• Kynurenine
• Neopterin
• Tandem Mass Spectrometry
• Tryptophan