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

Abstract

with other HLA alleles. 4,5,7,8 Furthermore, patients with HLA Susceptibility for type 1 autoimmune hepatitis has DR3 present at an earlier age and enter remission less frebeen associated with the major histocompatibility quently during corticosteroid therapy. 4,6,7 They also relapse alleles DRB1*0301, DRB3*0101, DRB1*0401, and after corticosteroid withdrawal, deteriorate during therapy, DRB4*0103, whereas the DRB1*1501 allele may protect and require liver transplantation more often than patients from the disease. Our aim was to determine if these alwith HLA DR4. [6][7][8][9][10] Because the alleles encompassing DR3 leles or others influence clinical manifestations and and DR4 encode specific amino acid sequences in the DRb prognosis. Eighty-six white patients were evaluated propolypeptide that determine the ability of each class II molespectively for immune features and outcomes. Class I cule to bind and present antigens to T cells, they can directly alleles were determined by microlymphocytotoxicity, influence the immunoreactivities of the effector cells responand class II alleles were assessed by polymerase chain reaction with sequence-specific oligonucleotide probes sible for the disease and, in turn, its clinical expression. 7 or sequence-specific primers. One hundred two white, Current nomenclature of the World Health Organization normal subjects were typed in the same fashion. Patients describes the specific HLA alleles rather than antigens. In with concurrent immunologic diseases were more com-this system, the genetic locus is first identified (i.e., DRB1), monly positive for DRB4*0103 than patients without followed by an asterisk and a four-figure code. The first two these features (68% vs. 38%, P Å .01). DRB1*0301 (86% vs. numbers of the code represent the old allelic group that often 45%, P Å .008) and the DRB1*0301-DRB3*0101 haplotype is equivalent to the serologically defined antigen. Thus, in (79% vs. 42%, P Å .02) occurred more commonly in pa-DRB1*04, the 04 represents DR4. The last two numbers refer tients who deteriorated during corticosteroid therapy. to the allele. Because there are 22 alleles of DR4 in the 1995 In contrast, DRB1*0401 and the DRB1*0401-DRB4*0103 nomenclature report, the DR4 alleles can range from haplotype were associated with a lower frequency of DRB1*0401 to DRB1*0422. death from liver failure or the need for transplantationRecent studies have indicated that DRB1*0301 is the printhan patients with other alleles (0% vs. 37%, P Å .03). cipal risk factor in white patients of northern European exPatients with DRB1*0301 differed from those with traction, that DRB1*0401 has a lesser degree of association, DRB1*0401 in that they were younger and failed treat-and that these two DRB1 alleles are independent markers of ment more commonly (27% vs. 5%, P Å .04). We conclude disease susceptibility. 3,7,12,13 Furthermore, the reported assothat alleles associated with susceptibility to type 1 auto-ciations with DRB3*0101 and DRB4*0103 may arise through immune hepatitis also influence its c...

Type 1 Autoimmune Hepatitis in Taiwan: Diagnosis Using the Revised Criteria of the International Autoimmune Hepatitis Group

“…Increased frequencies of HLA-B8, HLA-DR3, and HLA-DR4 in association with AIH were reported among white patients [29,30], and in Japan a high frequency of HLA-DR4 and HLA-BW54 was reported [31]. More recently, high-resolution DNA-based techniques have identified DRBI * 0301 and DRBI * 0401 as the main alleles associated with susceptibility and disease outcome for type 1 AIH [32]. No HLA typing data for TaiwaneseChinese patients have been reported previously.…”

Evidence of a Genetic Basis for the Different Geographic Occurrences of Liver/Kidney Microsomal Antibody Type 1 in Hepatitis C

“…Ninety-eight patients (96%) were tested for class I HLA (A and B loci) by standard microlymphocytotoxicity, and 102 patients were tested for class II HLA (DR and DQ loci) by polymerase chain reaction and sequence-specific primers (PCR-SSP), as reported previously [26,27]. The healthy control subjects resided in Olmsted County, Minnesota, and their ethnicity was similar to that of the North American patient population with chronic hepatitis C. Our study was approved by the institutional review boards of the University of Bologna and Mayo Clinic.…”

Autoantibodies as Prognostic Markers in Autoimmune Liver Disease

“…In the first instance, HLA DRB1*0301 and DRB1*0401 are the principal genetic risk factors [18,19], and in the second instance, DQB1*0201 (in strong linkage disequilibrium with HLA DRB1*07 and DRB1*03), is the principal genetic determinant [20]. These conventional serological markers of autoimmune hepatitis have been invaluable in directing the diagnosis, but they have been deficient as prognostic indices.…”