Analysis of HLA haplotypes in autoimmune hepatitis type 1: Identifying themajor susceptibility locus

Susceptibility to autoimmune hepatitis type I (AIH-1) has been associated w ith HLA-DR3, DR52, acid DR4 antigens in Caucasian and Oriental patients. Ho wever, in Brazil, disease susceptibility is primarily linked to DR13 and DR 52. In this highly admired population, we find different DR13-associated ha plotypes, presenting a unique opportunity to discriminate relevant genes wi thin a tightly linked genomic region. To identify the primary susceptibilit y locus, we sequenced DR13 alleles of 39 patients with AIH-1 and 22 control s. Patients were almost exclusively DRB1*1301, bur half of controls typed D RB1*1302. HLA-DQ haplotypes were varied. Oligotyping of DRD3 locus of all p atients and also within the HLA-DR13 positive group showed an allele distri bution comparable to controls, confirming that the stronger association lie s in the DRB1 locus. On the other hand, if DRB1*1301 is the major susceptib ility factor in our sample, the only amino acid different from DRB1*1302 in position 86, corresponding to pocket 1 in the peptide-presenting groove, m ay be important. We Propose that peptide presentation leading to pathogenes is of AIH-1 may ie quite stringent, but will also be affected by other stro ng genetic or environmental susceptibility factors, which would explain the various HLA molecules associated to the disease in the different populatio ns. (C) American Society for Histocompatibility and Immunogenetics, 2001. P ublished by Elsevier Science Inc.