Comparative analysis of portal cell infiltrates in antimitochondrial autoantibody-positive versus antimitochondrial autoantibody-negative primary biliary cirrhosis

Qinglong Jin, Yuki Moritoki, Ana Lleo, Koichi Tsuneyama, Pietro Invernizzi, Hitoshi Moritoki, Kentaro Kikuchi, Zhe Xiong Lian, Gideon M. Hirschfield, Aftab A. Ansari, Ross L. Coppel, M. Eric Gershwin, Junqi Niu

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

Substantial evidence supports dysregulated B-cell immune responses in patients with primary biliary cirrhosis (PBC), including the presence of serum antimitochondrial 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 AMAs, 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, because 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 observed in AMA - PBC patients. The portal areas from AMA - patients had a significant increase of cluster of differentiation (CD)5 + 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. Conclusion: Our data suggest a putative role of B-cell autoimmunity in regulating the portal destruction characteristic of PBC.

Original languageEnglish (US)
Pages (from-to)1495-1506
Number of pages12
JournalHepatology
Volume55
Issue number5
DOIs
StatePublished - May 2012

ASJC Scopus subject areas

  • Hepatology

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    Jin, Q., Moritoki, Y., Lleo, A., Tsuneyama, K., Invernizzi, P., Moritoki, H., Kikuchi, K., Lian, Z. X., Hirschfield, G. M., Ansari, A. A., Coppel, R. L., Gershwin, M. E., & Niu, J. (2012). Comparative analysis of portal cell infiltrates in antimitochondrial autoantibody-positive versus antimitochondrial autoantibody-negative primary biliary cirrhosis. Hepatology, 55(5), 1495-1506. https://doi.org/10.1002/hep.25511