Unmet Challenges in Immune-Mediated Hepatobiliary Diseases

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• 作者：Ulrich Beuers (1)
  M. Eric Gershwin (2)
  
  1. Department of Gastroenterology and Hepatology ; Tytgat Institute for Liver and Intestinal Research ; Academic Medical Center ; University of Amsterdam ; P.O. Box 22600 ; 1100 DD ; Amsterdam ; The Netherlands
  2. Division of Rheumatology ; Allergy and Clinical Immunology ; University of California at Davis School of Medicine ; Davis ; CA ; 95616 ; USA
  
• 关键词：Primary biliary cirrhosis ; Environmental factors ; Biologics ; Genetics ; Autoimmune hepatitis ; Progressive sclerosing cholangitis
• 刊名：Clinical Reviews in Allergy & Immunology
• 出版年：2015
• 出版时间：June 2015
• 年：2015
• 卷：48
• 期：2-3
• 页码：127-131
• 全文大小：140 KB
• 参考文献：1. Mackay, IR, Burnet, F (1963) Autoimmune Diseases. Charles C. Thomas, Springfield
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• 刊物主题：Allergology; Immunology; Internal Medicine;
• 出版者：Springer US
• ISSN：1559-0267

文摘

It is ironic that the liver, which serves a critical function in immune tolerance, itself becomes the victim of an autoimmune attack. Indeed, liver autoimmunity and the autoimmune diseases associated with both innate and adaptive responses to hepatocytes and/or cholangiocytes are models of human autoimmunity. For example, in primary biliary cirrhosis, there exists a well-defined and characteristic autoantibody and considerable homogeneity between patients. In autoimmune hepatitis, there are clinical characteristics that allow a rigorous subset definition and well-defined inflammatory infiltrates. In both cases, there are defects in a variety of immune pathways and including regulatory cells. In primary sclerosing cholangitis, with its characteristic overlap with inflammatory bowel disease, there are unique defects in innate immunity and particular important contribution of lymphoid homing to disease pathogenesis. In these diseases, as with other human autoimmune processes, there is the critical understanding that pathogenesis requires a genetic background, but is determined by environmental features, and indeed the concordance of these diseases in identical twins highlights the stochastic nature of immunopathology. Unfortunately, despite major advances in basic immunology and in immunopathology in these diseases, there remains a major void in therapy. The newer biologics that are so widely used in rheumatology, neurology, and gastroenterology have not yet seen success in autoimmune liver disease. Future efforts will depend on more rigorous molecular biology and systems analysis in order for successful application to be made to patients.