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.
Czaja
A J
AJ
Division of Gastroenterology and Internal Medicine, Mayo Clinic and Mayo Foundation, Rochester, MN 55905, USA.
Strettell
M D
MD
Thomson
L J
LJ
Santrach
P J
PJ
Moore
S B
SB
Donaldson
P T
PT
Williams
R
R
D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000483:Alleles; D000974:Antibodies, Antinuclear / Q000097:blood; D001327:Autoimmune Diseases / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology; D004198:Disease Susceptibility; D005260:Female; D005805:Genes, MHC Class I / Q000235:genetics*; D005802:Genes, MHC Class II / Q000235:genetics*; D006684:HLA-DR Antigens / Q000097:blood / Q000235:genetics; D006505:Hepatitis / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009130:Muscle, Smooth / Q000276:immunology; D017211:Treatment Failure
D000305:Adrenal Cortex Hormones; D000974:Antibodies, Antinuclear; D006684:HLA-DR Antigens