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Crohn's disease in the Japanese is associated with the HLA-DRw53
K Kobayashi1, M Atoh, A Yagita
1Department of Laboratory Medicine, National Defense Medical College, Tokorozawa, Japan.
Insights
Japanese Crohn
Area of Science:
- Immunogenetics
- Gastroenterology
- Human Leukocyte Antigen (HLA) system research
Background:
- The human leukocyte antigen (HLA) system plays a crucial role in immune responses.
- Genetic associations with inflammatory bowel diseases, including Crohn's disease (CD), are increasingly recognized.
- Previous studies have suggested a link between HLA antigens and CD susceptibility in various populations.
Purpose of the Study:
- To investigate the association between specific HLA antigens and Crohn's disease (CD) in a Japanese cohort.
- To explore both serological and genomic aspects of HLA antigen involvement in CD pathogenesis.
- To identify key HLA susceptibility factors in Japanese patients with CD.
Main Methods:
- Serological typing of HLA antigens in 30 Japanese CD patients and 54 healthy controls.
- Genomic analysis using restriction fragment length polymorphism (RFLP) with HLA-DR-B and DQ-B probes.
- Statistical analysis, including corrected p-values (pc), to determine significant associations.
Main Results:
- Significantly increased frequencies of HLA-DR4, DRw53, and DQw3 antigens were observed in CD patients compared to controls.
- Genomic analysis revealed increased prevalence of DRw53-specific PstI DR-B 2.6-kb and PstI DR-B 3.2-kb fragments in CD patients.
- No significant differences were found for DQw7, DQw8, or Class I HLA antigens between CD patients and controls.
Conclusions:
- The HLA-DRw53 antigen is strongly associated with Crohn's disease susceptibility in the Japanese population.
- Specific HLA-DR-B gene fragments are significantly more common in Japanese CD patients, suggesting a genetic predisposition.
- Further research into the specific subtypes of DR4 may elucidate more detailed associations with CD.
Abstract:
The association of Crohn's disease (CD) with the HLA system was investigated in Japanese patients by serological and genomic methods. HLA antigens were typed in 30 unrelated Japanese patients with CD and 54 healthy controls. The frequencies of HLA-DR4, DRw53 and DQw3 antigens were increased in CD (76.7, 86.7 and 80.0%) compared with controls [37.0%, p corrected (pc) = 0.007; 52.9%, pc = 0.001; 52.0%, pc = 0.009]. DQw7 and DQw8 antigens, the new split antigens of DQw3 produced by the TA10 antibody and linked to the DR4 and DRw53 antigens, were not significantly different in the DQw3-positive CD and controls. Class I antigens were not significantly different in the CD and controls. HLA-DR-B and DQ-B probes were used to study PstI-generated restriction fragment length polymorphism (RFLP) in CD and controls. The DRw53-specific PstI DR-B 2.6-kb fragment was increased in CD (88.0%) compared with controls (37.5%, pc = 5.6 X 10(-4)). The PstI DR-B 3.2-kb fragment was also increased in CD (80.0%) compared with controls (35.0%, pc = 5.6 X 10(-3)). It is reasonable to infer that the DRw53 is the most important susceptibility antigen in Japanese CD. The subtypes of the DR4 were determined by the hybridization of the DQ-B probe. The DQ-B PstI fragment patterns were not different in CD and controls.