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.
Scand J Gastroenterol. 2021 Apr;56(4):443-452. doi: 10.1080/00365521.2021.1880627. Epub 2021 Feb 14.
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.
炎症生物标志物在原发性硬化性胆管炎（PSC）中可能具有临床应用价值。我们旨在研究干扰素γ相关生物标志物新蝶呤和犬尿氨酸-色氨酸比值（KT-比值）在 PSC 中的作用。
使用 LC-MS/MS 在来自挪威、德国和瑞典的多个横断面队列中测量了循环新蝶呤、色氨酸和犬尿氨酸，该队列共包含 524 名 PSC 患者和 100 名健康对照者。
与对照组相比，PSC 患者的新蝶呤和 KT-比值在挪威的发现队列和验证队列中均显著升高。此外，在挪威发现队列和德国验证队列的 PSC 患者中，高水平的新蝶呤和 KT-比值与无肝移植生存相关。然而，在瑞典的验证 PSC 队列中，未观察到新蝶呤和 KT-比值与无肝移植生存之间的关系。在所有队列中，新蝶呤和 KT-比值之间的相关性为中度至强（rho 0.50-0.67）。新蝶呤和 KT-比值与 C 反应蛋白（rho 0.17-0.63）和改良 Mayo 风险评分（rho 0.23-0.42）在所有队列中均相关。
新蝶呤和 KT-比值在 PSC 中升高，并与两个独立的 PSC 队列的无肝移植生存相关，这突显了干扰素γ驱动的炎症在发病机制中的可能作用。然而，在一个队列中与生存无关联降低了新蝶呤和 KT-比值作为生物标志物的潜在临床价值，并强调了在多个队列中验证 PSC 新生物标志物的必要性。
