caa a22 4500 445888660 CHVBK 20180317145608.0 cr unu---uuuuu 170323e20110101xx s 000 0 eng 10.1007/s00535-010-0303-8 doi (NATIONALLICENCE)springer-10.1007/s00535-010-0303-8 Primary biliary cirrhosis and autoimmune hepatitis: apotopes and epitopes [Elektronische Daten] [Ana Lleo, Shinji Shimoda, Hiromi Ishibashi, M. Gershwin] Autoimmune liver diseases (ALDs) represent a wide spectrum of chronic inflammatory diseases that are characterized by an immune-mediated attack against either hepatocytes (in the case of autoimmune hepatitis types 1 and 2, AIH-1, 2) or cholangiocytes (in primary biliary cirrhosis, PBC). PBC is considered a model autoimmune disease due to the homogeneity of patients, the high specificity of antimitochondrial antibodies (AMAs), and the specificity of biliary epithelial cell (BEC) destruction. It ensues from a multi-lineage loss of tolerance to the E2 component of the pyruvate dehydrogenase complex (PDC-E2). One of the major unanswered questions in the pathogenesis of PBC is the specificity of small intrahepatic bile duct attack while PDC-E2 is present in mitochondria of nucleated cells. Recent findings suggest that the apoptosis of BECs may be of considerable importance for understanding PBC, and that they are more than simply an innocent victim of an immune attack. Rather, they attract immune attack by virtue of the unique biochemical mechanisms by which they handle PDC-E2. The role of apoptotic cells in AIH is not well defined, but advances in the study of autoreactive T cells stem mostly from AIH type 2, where the main autoantigen (CYP2D6) is known, enabling the characterization of antigen-specific immune responses. This review article is intended to provide a critical overview of current evidence on tissue specificity in ALDs, as well as the characteristics of the relevant epitopes and apotopes and their biological and clinical significance. Springer, 2010 Autoimmunity nationallicence Biliary epithelial cell nationallicence Hepatocyte nationallicence Apotope nationallicence Lleo Ana Division of Rheumatology, Allergy, and Clinical Immunology, University of California at Davis, Davis, CA, USA aut Shimoda Shinji Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan aut Ishibashi Hiromi Clinical Research Center, Nagasaki Medical Center, Nagasaki, Japan aut Gershwin M. Division of Rheumatology, Allergy, and Clinical Immunology, University of California at Davis, Davis, CA, USA aut Journal of Gastroenterology Springer Japan 46(2011-01-01), 29-38 0944-1174 46<29 2011 46 535 https://doi.org/10.1007/s00535-010-0303-8 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00535-010-0303-8 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Lleo Ana Division of Rheumatology, Allergy, and Clinical Immunology, University of California at Davis, Davis, CA, USA aut NATIONALLICENCE 700 1- Shimoda Shinji Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan aut NATIONALLICENCE 700 1- Ishibashi Hiromi Clinical Research Center, Nagasaki Medical Center, Nagasaki, Japan aut NATIONALLICENCE 700 1- Gershwin M. Division of Rheumatology, Allergy, and Clinical Immunology, University of California at Davis, Davis, CA, USA aut NATIONALLICENCE 773 0- Journal of Gastroenterology Springer Japan 46(2011-01-01), 29-38 0944-1174 46<29 2011 46 535 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer