This work is supported by The Roche Organ Transplantation Research Foundation (ROTRF), grant CI78133816 and the European FP7 HEPACUTE Project, grant 260844.
Article first published online: 5 FEB 2013
Copyright © 2012 American Association for the Study of Liver Diseases
Volume 57, Issue 2, pages 854–855, February 2013
How to Cite
Harris, H. J., Wilson, G. K., Hübscher, S. G. and McKeating, J. A. (2013), Heterogeneous claudin-1 expression in human liver. Hepatology, 57: 854–855. doi: 10.1002/hep.25910
Potential conflict of interest: Nothing to report.
- Issue published online: 5 FEB 2013
- Article first published online: 5 FEB 2013
- Accepted manuscript online: 22 JUN 2012 03:59AM EST
- Manuscript Accepted: 25 MAY 2012
- Manuscript Received: 24 MAY 2012
To the Editor:
We congratulate Mensa et al.1 on their report studying the expression of hepatitis C virus (HCV) receptors claudin-1 and occludin after liver transplantation and their influence on early viral kinetics. The authors provide a unique insight into the potential role receptor expression levels play in modulating early phase viral kinetics. They observed an association between HCV recurrence and hepatocellular claudin-1 and occludin expression levels expression during the first week post liver transplant. The authors confirm the results of previous reports showing increased claudin-1 expression in HCV-infected liver.2, 3 However, Mensa et al. conclude that claudin-1 is solely located at the apical pole of hepatocytes, in contrast to reports by Reynolds et al. and Zadori et al.2, 3 We agree that claudin-1 is predominantly expressed at the apical membrane of hepatocytes in normal liver; however, a minor pool of claudin-1 is observed at the basolateral membrane (Fig. 1). Basolateral expressed claudin-1 is more easily discerned when the liver section is co-stained with a marker for the hepatocellular membrane such as cytokeratin 8 (Fig. 1B), enabling one to observe heterogeneous patterns of localization across the liver parenchyma. The discrepancies between these studies are most likely explained by the imaging technique and analytical software employed. Spectral imaging of liver sections enables the accurate quantification of bound fluorescent antibody irrespective of signal intensity. However, volumetric imaging of claudin-1 at areas of high (apical) and low (basolateral) expression requires multiple threshold values (Fig. 1). In contrast, Mensa et al. quantified volumetric images of claudin-1 using a single threshold value, leading to a potential bias in their protein quantification and an underrepresentation of basolateral claudin-1. In conclusion, Mensa et al. have highlighted a role for viral receptor expression in defining HCV kinetics posttransplant, warranting further investigation to study the role of host pathways and inflammatory responses that regulate viral receptor hepatocellular expression.
- 1Hepatitis C virus receptors claudin-1 and occludin after liver transplantation and influence on early viral kinetics. HEPATOLOGY 2011; 53: 1436–1445., , , , , , et al.
- 2Hepatitis C virus receptor expression in normal and diseased liver tissue. HEPATOLOGY 2008; 47: 418–427., , , , , , et al.
- 3Examination of claudin-1 expression in patients undergoing liver transplantation owing to hepatitis C virus cirrhosis. Transplant Proc 2011; 43: 1267–1271., , , , , , et al.
H.J. Harris XX*, G.K. Wilson XX*, S.G. Hübscher XX*, J.A. McKeating XX*, * Institute of Biomedical Research and NIHR Liver Biomedical Research Unit, University of Birmingham, Birmingham, UK.