TY - JOUR
T1 - Comparative analysis of portal cell infiltrates in antimitochondrial autoantibody-positive versus antimitochondrial autoantibody-negative primary biliary cirrhosis
AU - Jin, Qinglong
AU - Moritoki, Yuki
AU - Lleo, Ana
AU - Tsuneyama, Koichi
AU - Invernizzi, Pietro
AU - Moritoki, Hitoshi
AU - Kikuchi, Kentaro
AU - Lian, Zhe Xiong
AU - Hirschfield, Gideon M.
AU - Ansari, Aftab A.
AU - Coppel, Ross L.
AU - Gershwin, M. Eric
AU - Niu, Junqi
PY - 2012/5
Y1 - 2012/5
N2 - 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 (-), 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.
AB - 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 (-), 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.
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U2 - 10.1002/hep.25511
DO - 10.1002/hep.25511
M3 - Article
C2 - 22135136
AN - SCOPUS:84859966851
VL - 55
SP - 1495
EP - 1506
JO - Hepatology
JF - Hepatology
SN - 0270-9139
IS - 5
ER -