ORIGINAL ARTICLE Mucosal Addressin Cell Adhesion Molecule (MAdCAM-1) Expression Is Upregulated in the Cirrhotic Liver and Immunolocalises to the Peribiliary Plexus and Lymphoid Aggregates Aftab Ala • David Brown • Korsa Khan • Richard Standish • Joseph A. Odin • M. Isabel Fiel • Thomas D. Schiano • Kenneth J. Hillan • Syed A. Rahman • Humphrey J. F. Hodgson • Amar P. Dhillon Received: 23 June 2012 / Accepted: 12 June 2013 Ó Springer Science+Business Media New York 2013 Abstract Background Enhanced cell expression of MAdCAM-1 is critical in tissue recruitment of lymphocytes in response to stimuli expressing the a4b7 integrin. MAdCAM-1 is well characterized in gut mucosa with emerging evidence of hepatic expression. Aims (i) Compare quantitative/semi-quantitatively MAd- CAM-1 expression in relation to early and advanced liver diseases (ii) Define the fine structure of vascular plexuses/ lymphatics in the portal tract on which MAdCAM-1 is expressed. Methods Using alkaline phosphatase anti-alkaline phos- phatase methodology on paraffin embedded tissue sections (n = 28) from cirrhotic individuals who underwent ortho- topic liver transplant, we evaluated MAdCAM-1 expression and compared with pre-cirrhotic, fulminant hepatitis B, and non-cirrhotic portal hypertension tissue sections. The posi- tive controls included normal colon tissue with negative controls without primary antibody and isotype-matched purified IgG. We developed a real time PCR to quantify levels of MAdCAM-1 mRNA in our samples. Results MAdCAM-1 was expressed in 27/28 of the cir- rhotic sections, localized primarily to septal areas within (i) endothelium of the peribiliary vascular plexus (PBP) (ii) lymphoid aggregates, with absence from normal, non- cirrhotic portal hypertension and pre-cirrhotic livers. There was significant upregulation of MAdCAM-1 mRNA in cir- rhosis (p \ 0.011), consistent with immunohistochemical analysis. A. Ala Faculty of Health & Medical Sciences and Faculty of Health Care Management & Policy, University of Surrey, Surrey GU2 7TE, UK A. Ala (&) Centre for Gastroenterology, Hepatology and Nutrition, Frimley Park Hospital NHS Foundation Trust, Surrey GU16 7UJ, UK e-mail: aftab.ala@fph-tr.nhs.uk D. Brown Á H. J. F. Hodgson Institute for Liver & Digestive Health, UCL Medical School, Royal Free Campus, London NW3 2PF, UK K. Khan Á R. Standish Á A. P. Dhillon Department of Cellular Pathology, UCL Medical School, Royal Free Campus, London NW3 2PF, UK J. A. Odin Á T. D. Schiano Division of Liver Diseases, Department of Medicine and Recanti/Miller Transplantation Institute, Icahn School of Medicine at Mount Sinai, Madison Avenue, New York, NY, USA M. I. Fiel Henry M. Stratton-Hans Popper Department of Pathology, Icahn School of Medicine at Mount Sinai, Madison Avenue, New York, NY, USA K. J. Hillan Institute of Pathology, GeneTech, South San Francisco, San Francisco, CA, USA S. A. Rahman European Molecular Biology Laboratory-European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, UK 123 Dig Dis Sci DOI 10.1007/s10620-013-2755-1