Digestive Diseases and Sciences

, Volume 47, Issue 10, pp 2139–2150 | Cite as

REVIEW: Genetic Bases of Autoimmune Hepatitis

  • Albert J. Czaja
  • Derek G. Doherty
  • Peter T. Donaldson
Article

Abstract

Our goal was to review the hypotheses in evolution that promise to elucidate the genetic bases of autoimmune hepatitis. DRB1*0301 and DRB1*0401 are the principal risk factors in Britain and the United States. Other susceptibility alleles in different ethnic groups commonly share the same or a similar motif at the critical DRβ71 position of the HLA class II molecule. Disease severity may be determined by the number of alleles encoding lysine at the DRβ71 position, the density of dimers presenting antigen, and the avidity of T-cell receptors for the displayed antigen. Concurrence on the same or different chromosomes of other nonspecific autoimmune promoters may also contribute. A negatively charged residue at the P4 position of antigenic peptides is preferred for binding to the disease-susceptibility alleles, and this complex may be recognized by promiscuous T cells. We conclude that autoimmune hepatitis is a model by which to study the genetic bases of autoimmunity.

autoimmune hepatitis autoimmunity autoantigens HLA 

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Copyright information

© Plenum Publishing Corporation 2002

Authors and Affiliations

  • Albert J. Czaja
    • 1
  • Derek G. Doherty
    • 2
    • 3
  • Peter T. Donaldson
    • 4
  1. 1.Division of Gastroenterology and HepatologyMayo Clinic and Mayo FoundationRochesterUSA
  2. 2.Education and Research CentreSt Vincent’s University HospitalDublin
  3. 3.Institute of Immunology, Department of BiologyNational University of IrelandMaynoothIreland
  4. 4.The Centre for Liver Research, Faculty of Clinical Medical Sciences, The Medical SchoolUniversity of NewcastleNewcastle-upon-TyneUK

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