Original Articles

Immunogenetics

, Volume 36, Issue 1, pp 49-55

First online:

A possible association between basic amino acids of position 13 of DRB1 chains and autoimmune hepatitis

  • Masao OtaAffiliated withDepartment of Legal Medicine, Shinshu University School of Medicine
  • , Takeshi SekiAffiliated withSecond Department of Internal Medicine, Shinshu University School ofMedicine
  • , Kendo KiyosawaAffiliated withSecond Department of Internal Medicine, Shinshu University School ofMedicine
  • , Seiichi FurutaAffiliated withSecond Department of Internal Medicine, Shinshu University School ofMedicine
  • , Kunihiko HinoAffiliated withSecond Department of Internal Medicine, National Defense Medical College
  • , Toshiro KondoAffiliated withSecond Department of Internal Medicine, National Defense Medical College
  • , Hirofumi FuskushimaAffiliated withSecond Department of Internal Medicine, National Defense Medical College
  • , Kimiyoshi TsujiAffiliated withSecond Department of Transplantation, Tokai University School of Medicine
  • , Hidetoshi InokoAffiliated withSecond Department of Transplantation, Tokai University School of Medicine

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Abstract

Fifty-one patients with autoimmune hepatitis have been studied for HLA association by conventional serology and also by modified polymerase chain reaction-restriction fragment lenght polymorphism (PCR-RFLP) genotyping.HLA-DR4 was significantly associated with autoimmmune hepatitis (46 of 51 patients, 90.2%). DNA typing of the DRB1 gene for 43 DR4-positive patients by using the PCR-RFLP technique revealed that of 43 patients, 33 had DRB1 * 0405 (Dw15), five had DRB1 * 0406 (DwKT2), four had DRB1 * 0403 (Dw13a), two had DRB1 * 0401 (Dw4), two of 43 had DRB1 * 0407 (Dw13b) and one had DRB1 * 0408 (Dw14b). Thus, there was no significant difference in Dw frequencies between DR4-positive patients and DR4-positive healthy subjects. These findings suggest that the DR4-specific sequence (Val 11 and His 13 at amino acid positions 11 and 13, respectively), but not particular Dw-associated DR4 sequence, in the first domain of the DRB1 chain contributes to susceptibility to autoimmune hepatitis among Japanese. Interestingly, all five of the DR4-negative patients had the DR2 specificity (DRB1 1502 or 1601). Taken together, these results imply that the basic amino acids at position 13, which is present only on the DR2 and DR4 B1 molecules (Arg on DR2 and His on DR4), are most important for determining the predisposition to autoimmune hepatitis.