Substitution of aspartic acid at position 57 of the DQbeta1 affects relapse of autoimmune pancreatitis.
OBJECTIVE
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 (ClinicalTrials.gov number, NCT00444444).
D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000483:Alleles; D000595:Amino Acid Sequence; D001224:Aspartic Acid / Q000235:genetics; D001327:Autoimmune Diseases / Q000188:drug therapy / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D006683:HLA-DQ Antigens / Q000737:chemistry / Q000235:genetics*; D059866:HLA-DQ beta-Chains; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010195:Pancreatitis / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology*; D011110:Polymorphism, Genetic; D011237:Predictive Value of Tests; D011239:Prednisolone / Q000627:therapeutic use; D012008:Recurrence; D012189:Retrospective Studies; D016896:Treatment Outcome
D000305:Adrenal Cortex Hormones; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D007166:Immunosuppressive Agents; D001224:Aspartic Acid; D011239:Prednisolone