TY - JOUR
T1 - Increased type-I interferon level is associated with liver damage and fibrosis in primary sclerosing cholangitis
AU - Salzmann, Rebekka J.S.
AU - Krötz, Christina
AU - Mocan, Tudor
AU - Mocan, Lavinia P.
AU - Grapa, Cristiana
AU - Rottmann, Sophia
AU - Reichelt, Ramona
AU - Keller, Cindy M.
AU - Langhans, Bettina
AU - Schünemann, Frederik
AU - Pohl, Alexander
AU - Böhler, Thomas
AU - Bersiner, Käthe
AU - Krawczyk, Marcin
AU - Milkiewicz, Piotr
AU - Sparchez, Zeno
AU - Lammert, Frank
AU - Gehlert, Sebastian
AU - Gonzalez-Carmona, Maria A.
AU - Willms, Arnulf
AU - Strassburg, Christian P.
AU - Kornek, Miroslaw T.
AU - Dold, Leona
AU - Lukacs-Kornek, Veronika
N1 - Publisher Copyright:
Copyright © 2024 The Author(s).
PY - 2024/2/14
Y1 - 2024/2/14
N2 - Background: The level of type-I interferons (IFNs) in primary sclerosing cholangitis (PSC) was investigated to evaluate its association with disease activity and progression. Methods: Bioactive type-I IFNs were evaluated in a murine model of PSC and human patients’ sera using a cell-based reporter assay and ELISA techniques. In total, 57 healthy participants, 71 PSC, and 38 patients with primary biliary cholangitis were enrolled in this study. Results: Bioactive type-I IFNs were elevated in the liver and serum of multidrug resistance protein 2–deficient animals and showed a correlation with the presence of CD45+ immune cells and serum alanine transaminase levels. Concordantly, bioactive type-I IFNs were elevated in the sera of patients with PSC as compared to healthy controls (sensitivity of 84.51%, specificity of 63.16%, and AUROC value of 0.8267). Bioactive IFNs highly correlated with alkaline phosphatase (r = 0.4179, p < 0.001), alanine transaminase (r = 0.4704, p < 0.0001), and gamma-glutamyl transpeptidase activities (r = 0.6629, p < 0.0001) but not with serum bilirubin. In addition, patients with PSC with advanced fibrosis demonstrated significantly higher type-I IFN values. Among the type-I IFN subtypes IFNα, β and IFNω could be detected in patients with PSC with IFNω showing the highest concentration among the subtypes and being the most abundant among patients with PSC. Conclusions: The selectively elevated bioactive type-I IFNs specifically the dominating IFNω could suggest a novel inflammatory pathway that might also have a hitherto unrecognized role in the pathomechanism of PSC.
AB - Background: The level of type-I interferons (IFNs) in primary sclerosing cholangitis (PSC) was investigated to evaluate its association with disease activity and progression. Methods: Bioactive type-I IFNs were evaluated in a murine model of PSC and human patients’ sera using a cell-based reporter assay and ELISA techniques. In total, 57 healthy participants, 71 PSC, and 38 patients with primary biliary cholangitis were enrolled in this study. Results: Bioactive type-I IFNs were elevated in the liver and serum of multidrug resistance protein 2–deficient animals and showed a correlation with the presence of CD45+ immune cells and serum alanine transaminase levels. Concordantly, bioactive type-I IFNs were elevated in the sera of patients with PSC as compared to healthy controls (sensitivity of 84.51%, specificity of 63.16%, and AUROC value of 0.8267). Bioactive IFNs highly correlated with alkaline phosphatase (r = 0.4179, p < 0.001), alanine transaminase (r = 0.4704, p < 0.0001), and gamma-glutamyl transpeptidase activities (r = 0.6629, p < 0.0001) but not with serum bilirubin. In addition, patients with PSC with advanced fibrosis demonstrated significantly higher type-I IFN values. Among the type-I IFN subtypes IFNα, β and IFNω could be detected in patients with PSC with IFNω showing the highest concentration among the subtypes and being the most abundant among patients with PSC. Conclusions: The selectively elevated bioactive type-I IFNs specifically the dominating IFNω could suggest a novel inflammatory pathway that might also have a hitherto unrecognized role in the pathomechanism of PSC.
UR - http://www.scopus.com/inward/record.url?scp=85206936284&partnerID=8YFLogxK
U2 - 10.1097/HC9.0000000000000380
DO - 10.1097/HC9.0000000000000380
M3 - Article
C2 - 38358371
AN - SCOPUS:85206936284
SN - 2471-254X
VL - 8
JO - Hepatology Communications
JF - Hepatology Communications
IS - 3
M1 - e0380
ER -