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Infiltration of inflammatory cells expressing mitochondrial proteins around bile ducts and in biliary epithelial layer may be involved in the pathogenesis in primary biliary cirrhosis
  1. Motoko Sasaki,
  2. Yuko Kakuda,
  3. Masami Miyakoshi,
  4. Yasunori Sato,
  5. Yasuni Nakanuma
  1. Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan
  1. Correspondence to Dr Motoko Sasaki, Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa 920-8640, Japan; m8sasaki{at}med.kanazawa-u.ac.jp

Abstract

Aims Serum antimitochondrial antibodies are characteristic in most patients with primary biliary cirrhosis (PBC); however, the significance of antimitochondrial antibodies in the pathogenesis of PBC remains unclear. We examined the extent and types of mitochondrial protein-expressing inflammatory cells and its association with deregulated autophagy of mitochondria in biliary epithelial lesions in PBC.

Methods We examined the expression of pyruvate dehydrogenase complex-E2 component and a mitochondrial protein cytochrome c oxidase, subunit I in inflammatory cells in livers taken from patients with PBC (n=35) and control livers (n=64) including primary sclerosing cholangitis. Mitochondrial protein-expressing inflammatory cells were characterised by double immunofluorescence with surface markers.

Results Infiltration of mitochondrial protein-expressing inflammatory cells was mainly observed in portal tracts and in the biliary epithelial layer and around the damaged small bile ducts in PBC. The extent of infiltration in portal tracts was significantly higher in PBC and early stage of chronic viral hepatitis than normal livers. The extent of infiltration around bile ducts and in biliary epithelial layer was significantly higher in early stage of PBC than control livers. Mitochondrial protein-expressing inflammatory cells included (1) CD68 and/or myeloperoxidase -positive monocytes/macrophages and (2) CD79a, CD38, CD138, IgM-positive and/or IgG-positive plasma cells. Colocalised expression of pyruvate dehydrogenase complex-E2 component and autophagy marker light chain 3β was observed in the inflammatory cells.

Conclusions Mitochondrial protein-expressing inflammatory cells infiltrating around the damaged bile ducts and in biliary epithelial layers may be closely associated with the pathogenesis of bile duct lesion in PBC.

  • Auto-Immune Biliary Disease
  • Liver Disease
  • Autoimmunity

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