title: Primary sclerosing cholangitis in two brothers: report of a family with special emphasis on molecular HLA and MICA genotyping.
abstract: Immune mechanisms play a role in the pathogenesis of primary sclerosing cholangitis (PSC), as suggested by its association with certain HLA haplotypes. Genetic predisposition is supported by its occurrence in families, but data are scarce. Our aim is to report on two brothers with PSC, and to investigate HLA and MICA alleles in this family. The clinical, biochemical, radiological, and pathological findings in two brothers with PSC as well as in their sister and parents were reviewed. Molecular genotyping of HLA class II and MICA alleles was performed in all five family members. In two brothers, p-ANCA positive PSC was found. The youngest also had ulcerative colitis, and had evolved into cirrhosis at the age of 17 years. Their mother had positive p-ANCA and mild cholestatic changes. Their father and sister were unaffected. Both brothers were homozygous for the MICA*00801 allele, and were positive for the susceptibility HLA haplotypes DR3-DQ2 and DR6-DQ6. Their unaffected father and sister both carried the protective DR4 allele. The presence of PSC in two brothers, and the distribution of HLA haplotypes and MICA alleles, adds supportive evidence for an immunogenetic origin of PSC.
authors.affiliation: Unit for Liver Diseases, Department of Internal Medicine, University Hospital Gasthuisberg, Belgium. werner.vansteenbergen@uz.kuleuven.ac.be
authors.forename: Werner
authors.initials: W
authors.lastname: Van Steenbergen
authors.forename: Eric
authors.initials: E
authors.lastname: De Goede
authors.forename: Marie-Paule
authors.initials: MP
authors.lastname: Emonds
authors.forename: Judith
authors.initials: J
authors.lastname: Reinders
authors.forename: Marcel
authors.initials: M
authors.lastname: Tilanus
authors.forename: Johan
authors.initials: J
authors.lastname: Fevery
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D015209:Cholangitis, Sclerosing / Q000235:genetics*; D005192:Family Health; D005260:Female; D005838:Genotype; D006683:HLA-DQ Antigens / Q000235:genetics; D006684:HLA-DR Antigens / Q000235:genetics; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics; D035781:Siblings
chemical_list: D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; C099187:MHC class I-related chain A