title: Lack of HLA predominance and HLA shared epitopes in biliary Atresia.
abstract: Biliary atresia (BA) is characterized by progressive inflammation and fibrosis of bile ducts. A theory of pathogenesis entails autoimmune-mediated injury targeting bile duct epithelia. One of the strongest genetic associations with autoimmunity is with HLA genes. In addition, apparently dissimilar HLA alleles may have similar antigen-binding sites, called shared epitopes, that overlap in their capacity to present antigens. In autoimmune disease, the incidence of the disease may be related to the presence of shared epitopes, not simply the HLA allelic association.
  
  
  OBJECTIVE
  To determine HLA allele frequency (high-resolution genotyping) and shared epitope associations in BA.
  
  
  RESULTS
  Analysis of every allele for HLA-A, -B, -C, -DRB1, -DPB1 and -DQB1 in 180 BA and 360 racially-matched controls did not identify any significant HLA association with BA. Furthermore, shared epitope analysis of greater than 10 million possible combinations of peptide sequences was not different between BA and controls.
  
  
  CONCLUSIONS
  This study encompasses the largest HLA allele frequency analysis for BA in the United States and is the first study to perform shared epitope analysis. When controlling for multiple comparisons, no HLA allele or shared epitope association was identified in BA. Future studies of genetic links to BA that involve alterations of the immune response should include investigations into defects in regulatory T cells and non-HLA linked autoinflammatory diseases.
authors.affiliation: Departments of Medicine and Immunology, Division of Allergy and Clinical Immunology, University of Colorado School of Medicine, 80045 Aurora, CO USA ; Department of Pediatrics, Division of Pediatric Gastroenterology, Digestive Health Institute, Children's Hospital Colorado, Hepatology and Nutrition, 13123 East 16th Ave. B290, 80045 Aurora, CO USA.
authors.forename: Cara L
authors.initials: CL
authors.lastname: Mack
authors.forename: Kirsten M
authors.initials: KM
authors.lastname: Anderson
authors.forename: Michael T
authors.initials: MT
authors.lastname: Aubrey
authors.forename: Philip
authors.initials: P
authors.lastname: Rosenthal
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Sokol
authors.forename: Brian M
authors.initials: BM
authors.lastname: Freed