Substitution of aspartic acid at position 57 of the DQbeta1 affects relapse of autoimmune pancreatitis

Gastroenterology. 2008 Feb;134(2):440-6. doi: 10.1053/j.gastro.2007.11.023. Epub 2007 Nov 17.


Background & aims: Although autoimmune pancreatitis (AIP) responds well to corticosteroid therapy, relapse during maintenance corticosteroid therapy or after the withdrawal of corticosteroid treatment is not uncommon. To date, the factors related to relapse of AIP have not been fully explored.

Methods: To determine the clinical and genetic predictors relating to the relapse of AIP, we evaluated clinical factors, HLA polymorphisms, and the amino acid sequences in 40 patients with AIP.

Results: At a median follow-up period of 40 months (range, 12-67 months), relapse developed in 13 of 40 patients with AIP (33%), in whom complete remission was achieved with oral corticosteroid therapy. Among demographics, clinical characteristics in the initial diagnosis of AIP, we could not find any clinical predictor for relapse of AIP; however, in amino acid sequence analysis for relapse of AIP, the substitution of aspartic acid to nonaspartic acid at residue 57 of DQbeta1 showed a significant association with relapse of AIP (nonrelapse group, 29.6%; relapse group, 100%; P = .00003; odds ratio, 3.38; 95% confidence interval, 1.9-6.0). There was a significant difference in the timing of relapse of AIP, according to density of the nonaspartic acid residue at DQbeta1 57 (nonaspartic acid homozygosity: mean +/- SD, 6.7 +/- 4.2 months; nonaspartic acid heterozygosity: mean +/- SD, 33 +/- 11 months; P < .001).

Conclusions: Substitution of aspartic acid to nonaspartic acid at DQbeta1 57 appears to represent a key genetic factor for relapse of AIP ( number, NCT00444444).

MeSH terms

  • Adrenal Cortex Hormones / therapeutic use
  • Adult
  • Aged
  • Alleles
  • Amino Acid Sequence
  • Aspartic Acid / genetics
  • Autoimmune Diseases / drug therapy
  • Autoimmune Diseases / genetics*
  • Dose-Response Relationship, Drug
  • Female
  • Follow-Up Studies
  • Genetic Predisposition to Disease
  • HLA-DQ Antigens / chemistry
  • HLA-DQ Antigens / genetics*
  • HLA-DQ beta-Chains
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Pancreatitis / drug therapy
  • Pancreatitis / genetics*
  • Pancreatitis / immunology*
  • Polymorphism, Genetic
  • Predictive Value of Tests
  • Prednisolone / therapeutic use
  • Recurrence
  • Retrospective Studies
  • Treatment Outcome


  • Adrenal Cortex Hormones
  • HLA-DQ Antigens
  • HLA-DQ beta-Chains
  • HLA-DQB1 antigen
  • Immunosuppressive Agents
  • Aspartic Acid
  • Prednisolone

Associated data