The immunopathology of liver granulomas in primary biliary cirrhosis.
Liver granulomas and elevated serum IgM are commonly observed in patients with primary biliary cirrhosis (PBC) but their pathogenetic significance remains largely unknown. To address this issue we performed an extensive immunostaining and colocalization study of markers associated with dendritic cells and IgM in a large cohort of tissue samples from PBC and control livers as well as from non-hepatic granulomatous diseases. First, the classical dendritic cell CD11c marker is highly expressed and more sensitive than classical hematoxylin-eosin staining in detecting granulomas associated with PBC and other conditions. Second, PBC cases with CD11c-positive granulomas have significantly higher serum IgM levels and earlier disease stages. Third, granulomas from PBC and other diseases demonstrate markers of dendritic cell immaturity, i.e. CD11b, reduced MHC II, IL-23, CCR7 and CD83 expression, and elevated C1q expression. Lastly, B cells and IgM-positive plasma cells are largely represented around PBC granulomas along with macrophages. In conclusion, our comprehensive immunohistochemical study suggests that dendritic cells are key to the pathogenesis of granulomas, regardless of their origin. More specifically, PBC liver granulomas may result from the interaction between immature dendritic cells and IgM.
Department of Gastroenterology, Shanghai Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Institute of Digestive Disease, 145 Shandong Middle Road, Shanghai 200001, China.
Zhengrui
Z
You
Qixia
Q
Wang
Zhaolian
Z
Bian
Yuan
Y
Liu
Xiaofeng
X
Han
Yanshen
Y
Peng
Lei
L
Shen
Xiaoyu
X
Chen
Dekai
D
Qiu
Carlo
C
Selmi
M Eric
ME
Gershwin
Xiong
X
Ma
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006099:Granuloma / Q000150:complications / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007075:Immunoglobulin M / Q000097:blood / Q000276:immunology*; D007150:Immunohistochemistry; D008099:Liver / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008105:Liver Cirrhosis, Biliary / Q000150:complications / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010950:Plasma Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology
D015703:Antigens, CD; D015415:Biomarkers; D007075:Immunoglobulin M