Comparative analysis of portal cell infiltrates in AMA positive versus AMA negative PBC

• Type of Material: Article
• Authors: Qinglong Jin, University of Jilin; Yuki Moritoki, Akita University; Ana Lleo, IRCCS Istituto Clinico Humanitas; Koichi Tsuneyama, University of Toyama; Pietro Invernizzi, IRCCS Istituto Clinico Humanitas; Hitoshi Moritoki, Moritoki Laboratory of Plasticity; Kentaro Kikuchi, Teikyo University; Zhe-Xiong Lian, University of Science and Technology of China; Gideon M. Hirschfield, University of Toronto; Aftab A Ansari, Emory University; Ross L. Coppel, Monash University; M. Eric Gershwin, University of California; Junqi Niu, University of Jilin
• Language: English
• Date: 2012-05
• Publisher: Wiley-Blackwell
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2011 American Association for the Study of Liver Diseases
• Final Published Version (URL): http://onlinelibrary.wiley.com/doi/10.1002/hep.25511/abstract;jsessionid=93BE47B6844CDE870E13B9E9E3405AD3.d03t04
• Title of Journal or Parent Work: Hepatology
• ISSN: 0270-9139
• Volume: 55
• Issue: 5
• Start Page: 1495
• End Page: 1506
• Grant/Funding Information: This study was supported by grants from National Institutes of Health grant DK39588 and from the Eleventh Five-year Plan for AIDS and Viral Hepatitis (No. 2008ZX10002-004), Ministry of Health (No. 20073531), National Natural Science Foundation of China (No. 30771912 and 30972610), Grant-in-Aid for Scientific Research (C) and Grant-in-Aid for Research Activity start-up of Japan Society of the Promotion of Science KAKENHI (No. 21590433 and 22890024) and Jilin Province Science and Technology Agency (No. 200705128).
• Keywords: CD5; B cells; CD20; Primary biliary cirrhosis
• Research Categories: Health Sciences, Immunology

Abstract

Substantial evidence supports dysregulated B cell immune responses in patients with primary biliary cirrhosis (PBC), including the presence of serum anti-mitochondrial antibodies (AMAs). However, recent reports from murine models of PBC suggest that B cells may also provide regulatory function and indeed the absence of B cells in such models leads to exacerbation of disease. The vast majority of patients with PBC have readily detectable antimitochondrial antibodies, but a minority (<5%), are AMA negative (AMA−) even with recombinant diagnostic technology. This issue prompted us to examine the nature of B cell infiltrates surrounding the portal areas in AMA positive (AMA+) and AMA− patients since they display indistinguishable clinical features. Of importance was the finding that the degree of bile duct damage around the portal areas was significantly milder in AMA+ PBC than those seen in AMA− PBC patients. The portal areas from AMA− patients had a significant increase of CD5+ cells infiltrating the ductal regions and the levels of B cell infiltrates were worse in the early phase of bile duct damage. The frequency of positive portal areas and the magnitude of CD5+ and CD20+ cellular infiltrates within areas of ductal invasion is associated with the first evidence of damage of biliary duct epithelia, but becomes reduced in the ductopenia stage, with the exception of CD5+ cells which remain sustained and predominate over CD20+ cells. In conclusion, our data suggest a putative role of B cell autoimmunity in regulating the portal destruction characteristic of PBC.