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Genetic polymorphism of HLA-DR in the Japanese population
1Department of Immunology, School of Medicine, Kitasato University, Kanagawa, Japan.
Insights
DNA typing identified new HLA-DRB1 alleles in Japanese populations. This method revealed higher frequencies for DR13 and DR14 alleles and identified a specific allele linked to juvenile rheumatoid arthritis (JRA).
Area of Science:
- Immunogenetics
- Molecular Biology
- Human Genetics
Background:
- Immunological methods for HLA-DR typing have limitations in identifying all alleles.
- Previous studies on HLA-DR and disease associations in Japanese populations may be incomplete due to typing limitations.
Purpose of the Study:
- To identify novel HLA-DRB1 alleles in the Japanese population using sequence analysis.
- To establish a comprehensive DNA typing method for HLA-DRB1 alleles in Japanese individuals.
- To investigate the association of specific HLA-DRB1 alleles with juvenile rheumatoid arthritis (JRA) and unexplained recurrent spontaneous abortion (URSA).
Main Methods:
- Sequence analysis of HLA-DRB1 genes from Japanese donors.
- Development and application of sequence-specific oligonucleotide (SSO) probes for DNA typing.
- Gene frequency calculation based on SSO-DNA typing.
- Application of DR-DNA typing to patients with JRA and URSA.
Main Results:
- Three new DRB1 alleles (DRB1-12b, DRB1-14c, DRB1-JX6) were identified.
- SSO-DNA typing provided comprehensive DRB typing for the Japanese population, revealing higher DR13 and DR14 frequencies than serological methods.
- DRB1*0405 was identified as a susceptibility allele for rheumatoid factor-positive polyarticular JRA.
- No correlation was found between URSA and specific DR types, contradicting some previous serological findings.
Conclusions:
- Sequence-specific oligonucleotide (SSO)-DNA typing is a powerful tool for comprehensive HLA-DRB1 allele identification and frequency determination in populations.
- This method offers improved accuracy over serological typing for HLA-DR alleles.
- DRB1*0405 is implicated in the pathogenesis of rheumatoid factor-positive polyarticular JRA in Japanese patients.
- HLA-DR typing does not appear to be a significant factor in unexplained recurrent spontaneous abortion (URSA).
Abstract:
As a result of carrying out sequence analyses on the HLA-DR genes of several Japanese donors, we found three new DRB1 alleles, DRB1-12b, DRB1-14c, and DRB1-JX6, that had not been identified using immunological procedures. Sequence-specific oligonucleotide (SSO) probes directed against various DRB1 alleles, including the above three, enabled DNA typing of all the DRB types in the Japanese population and calculation of their gene frequencies based on this typing to be carried out for the first time. The SSO-DNA typing yielded higher DR13 and DR14 gene frequencies than those reported by serological workshops. Next, we applied this DR-DNA typing to the analysis of Japanese patients with juvenile rheumatoid arthritis (JRA) and found that DRB1*0405 was the allele susceptible to rheumatoid factor-positive polyarticular JRA, which is one of the four types of JRA that has been classified clinically. Analysis of the DR types of patients who suffered unexplained recurrent spontaneous abortion (URSA) using DNA typing demonstrated that 1) URSA is not correlated with any particular DR type and 2) no difference between the DR sharing rate of patients and normal couple was detected, which contradicts the results obtained in some serological studies.