Associations between alleles of the major histocompatibility complex and type 1 autoimmune hepatitis

Susceptibility for type 1 autoimmune hepatitis has been associated with the major histocompatibility alleles DRB1*0301, DRB3*0101, DRB1*0401, and DRB4*0103, whereas the DRB1*1501 allele may protect from the disease, Our aim was to determine if these alleles or others influence clinical manifestations and prognosis, Eighty-six white patients were evaluated prospectively for immune features and outcomes, Class I alleles were determined by microlymphocytotoxicity, and class II alleles were assessed by polymerase chain reaction with sequence-specific oligonucleotide probes or sequence-specific primers, One hundred two white, normal subjects were typed in the same fashion, Patients with concurrent immunologic diseases were more commonly positive for DRB4*0103 than patients without these features (68% vs, 38%, P = .01), DRB1*0301 (86% vs, 45%, P = .008) and the DRB1*0301-DRB3*0101 haplotype (79% vs, 42%, P = .02) occurred more commonly in patients who deteriorated during corticosteroid therapy, In contrast, DRB1*0401 and the DRB1*0401-DRB4*0103 haplotype were associated with a lower frequency of death from liver failure or the need for transplantation than patients with other alleles (0% vs, 37%, P = .03), Patients with DRB1*0301 differed from those with DRB1*0401 in that they were younger and failed treatment more commonly (27% vs, 5%, P = .04), We conclude that alleles associated with susceptibility to type 1 autoimmune hepatitis also influence its clinical features and prognosis, DRB4*0103 is associated with concurrent immune diseases, DRB1*0301 with a poor treatment response, and DRB1*0401 with a lower frequency of hepatic death or transplantation.