Genes and (auto)immunity in primary biliary cirrhosis

Genes and (auto)immunity in primary biliary cirrhosis

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ABSTRACT Primary biliary cirrhosis (PBC) is a chronic autoimmune cholestatic liver disease most commonly encountered in postmenopausal women; it is characterized by high-titer serum autoantibodies to mitochondrial antigens, elevated serum IgM, progressive destruction of intrahepatic bile ducts, and ultimately liver cirrhosis and failure. The cytopathic mechanisms leading to the selective destruction of intrahepatic cholangiocytes are still largely unknown. The current theory on the pathogenesis of PBC indicated that environmental factors might trigger autoimmunity in genetically susceptible individuals. In fact, genetic predisposition is critical to disease onset and progression, yet peculiar among autoimmune diseases, as indicated by the lack of a strong association with major histocompatibility complex haplotypes. Further, the recently reported concordance rate among monozygotic twins strenghtens the importance of genetic factors, while also indicating that additional factors, possibly infectious agents or xenobiotics, intervene to trigger the disease. In this review, the available data regarding the genetic factors associated with PBC susceptibility and progression, as well as the available evidence regarding the immunomediated pathogenesis of PBC, will be critically illustrated and discussed. Access through your institution Buy or subscribe This is a preview of subscription content, access via your institution ACCESS OPTIONS Access through your institution Subscribe to this journal Receive 6 digital issues and online access to articles $119.00 per year only $19.83 per issue Learn more Buy this article * Purchase on SpringerLink * Instant access to full article PDF Buy now Prices may be subject to local taxes which are calculated during checkout ADDITIONAL ACCESS OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS DISSECTING CAUSAL RELATIONSHIPS BETWEEN PRIMARY BILIARY CHOLANGITIS AND EXTRAHEPATIC AUTOIMMUNE DISEASES BASED ON MENDELIAN RANDOMIZATION Article Open access 21 May 2024 RISK OF HEPATOCELLULAR CARCINOMA AND CIRRHOSIS DECOMPENSATION IN A LARGE RETROSPECTIVE COHORT OF CIRRHOTIC PATIENTS WITH AUTOIMMUNE HEPATITIS Article Open access 16 April 2025 _MARC1_ P.A165T VARIANT IS ASSOCIATED WITH DECREASED MARKERS OF LIVER INJURY AND ENHANCED ANTIOXIDANT CAPACITY IN AUTOIMMUNE HEPATITIS Article Open access 23 December 2021 REFERENCES * Talwalkar JA, Lindor KD . 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CAS  PubMed  Google Scholar  Download references AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Division of Internal Medicine, San Paolo School of Medicine, University of Milan, Milan, Italy C Selmi, P Invernizzi, M Zuin & M Podda * Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis, Davis, 95616, CA, USA C Selmi, M F Seldin & M E Gershwin * Biochemistry and Rowe Program in Human Genetics, University of California at Davis, School of Medicine, Davis, CA, USA M F Seldin Authors * C Selmi View author publications You can also search for this author inPubMed Google Scholar * P Invernizzi View author publications You can also search for this author inPubMed Google Scholar * M Zuin View author publications You can also search for this author inPubMed Google Scholar * M Podda View author publications You can also search for this author inPubMed Google Scholar * M F Seldin View author publications You can also search for this author inPubMed Google Scholar * M E Gershwin View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to M E Gershwin. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Selmi, C., Invernizzi, P., Zuin, M. _et al._ Genes and (auto)immunity in primary biliary cirrhosis. _Genes Immun_ 6, 543–556 (2005). https://doi.org/10.1038/sj.gene.6364248 Download citation * Received: 17 June 2005 * Accepted: 17 June 2005 * Published: 21 July 2005 * Issue Date: 01 October 2005 * DOI: https://doi.org/10.1038/sj.gene.6364248 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get shareable link Sorry, a shareable link is not currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative KEYWORDS * autoimmune cholangitis * complex disease * association study * environmental factors * pathogenesis

ABSTRACT Primary biliary cirrhosis (PBC) is a chronic autoimmune cholestatic liver disease most commonly encountered in postmenopausal women; it is characterized by high-titer serum


autoantibodies to mitochondrial antigens, elevated serum IgM, progressive destruction of intrahepatic bile ducts, and ultimately liver cirrhosis and failure. The cytopathic mechanisms


leading to the selective destruction of intrahepatic cholangiocytes are still largely unknown. The current theory on the pathogenesis of PBC indicated that environmental factors might


trigger autoimmunity in genetically susceptible individuals. In fact, genetic predisposition is critical to disease onset and progression, yet peculiar among autoimmune diseases, as


indicated by the lack of a strong association with major histocompatibility complex haplotypes. Further, the recently reported concordance rate among monozygotic twins strenghtens the


importance of genetic factors, while also indicating that additional factors, possibly infectious agents or xenobiotics, intervene to trigger the disease. In this review, the available data


regarding the genetic factors associated with PBC susceptibility and progression, as well as the available evidence regarding the immunomediated pathogenesis of PBC, will be critically


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subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS DISSECTING CAUSAL RELATIONSHIPS BETWEEN PRIMARY BILIARY CHOLANGITIS AND EXTRAHEPATIC


AUTOIMMUNE DISEASES BASED ON MENDELIAN RANDOMIZATION Article Open access 21 May 2024 RISK OF HEPATOCELLULAR CARCINOMA AND CIRRHOSIS DECOMPENSATION IN A LARGE RETROSPECTIVE COHORT OF


CIRRHOTIC PATIENTS WITH AUTOIMMUNE HEPATITIS Article Open access 16 April 2025 _MARC1_ P.A165T VARIANT IS ASSOCIATED WITH DECREASED MARKERS OF LIVER INJURY AND ENHANCED ANTIOXIDANT CAPACITY


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Scholar  Download references AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Division of Internal Medicine, San Paolo School of Medicine, University of Milan, Milan, Italy C Selmi, P


Invernizzi, M Zuin & M Podda * Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis, Davis, 95616, CA, USA C Selmi, M F Seldin & M E Gershwin


* Biochemistry and Rowe Program in Human Genetics, University of California at Davis, School of Medicine, Davis, CA, USA M F Seldin Authors * C Selmi View author publications You can also


search for this author inPubMed Google Scholar * P Invernizzi View author publications You can also search for this author inPubMed Google Scholar * M Zuin View author publications You can


also search for this author inPubMed Google Scholar * M Podda View author publications You can also search for this author inPubMed Google Scholar * M F Seldin View author publications You


can also search for this author inPubMed Google Scholar * M E Gershwin View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR


Correspondence to M E Gershwin. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Selmi, C., Invernizzi, P., Zuin, M. _et al._ Genes and (auto)immunity in


primary biliary cirrhosis. _Genes Immun_ 6, 543–556 (2005). https://doi.org/10.1038/sj.gene.6364248 Download citation * Received: 17 June 2005 * Accepted: 17 June 2005 * Published: 21 July


2005 * Issue Date: 01 October 2005 * DOI: https://doi.org/10.1038/sj.gene.6364248 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get shareable


link Sorry, a shareable link is not currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative KEYWORDS * autoimmune


cholangitis * complex disease * association study * environmental factors * pathogenesis