Genetic bases of autoimmune hepatitis.
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 DRbeta71 position of the HLA class II molecule. Disease severity may be determined by the number of alleles encoding lysine at the DRbeta1 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.
Czaja
Albert J
AJ
Division of Gastroenterology and Hepatology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905, USA.
Doherty
Derek G
DG
Donaldson
Peter T
PT
D000483:Alleles; D003431:Cross-Cultural Comparison; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006684:HLA-DR Antigens / Q000235:genetics; D059811:HLA-DRB1 Chains; D019693:Hepatitis, Autoimmune / Q000235:genetics*; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D006801:Humans; D008297:Male; D012737:Sex Factors; D006113:United Kingdom; D014481:United States
D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C553502:HLA-DRB1*03:01 antigen; C553505:HLA-DRB1*04:01 antigen; D000949:Histocompatibility Antigens Class II