OBJECTIVE--To assess the relationship between HLA-DRB1 genotypes and the progression of bone destruction in Japanese patients with RA. METHODS--The HLA-DRB1 alleles were determined by polymerase chain reaction and allele specific oligonucleotide probe techniques in 160 Japanese patients with RA. HLA-DR 0101, 0401, 0404, 0405, 1001 and 1402 were regarded as susceptible alleles of RA according to previous reports. Patients were classified into three groups (S/S, S/N and N/N group), based on the possession of two, one or no susceptible factor. The grading of radio-graphic changes in the wrists and fingers were evaluated by Larsen's criteria. The radiographic grades were first compared with the results of genotyping in the 160 cross sectional cases. A retrospective study was then conducted on a subgroup consisting of 57 cases taken from the 160 cases used for the cross sectional study. RESULTS--In the scatter diagram of the 160 cross sectional cases expressing the relationship between the stage of bone destruction and duration of RA, the regression line and the 95% confidence intervals separated the S/S group from the S/N and N/N groups in the early phase of development of bone destruction. In the retrospective study on the 57 cases the median years taken to development to stage V in the wrists after the onset of symptoms were 13.1 in the patients in the S/S group, 22.7 in the S/N group and 23.0 in the N/N group. The difference observed between the S/S and S/N group, and between the S/S and N/N group were statistically significant (p < 0.01), but that between the S/N and N/N groups was not. Thus the bone destruction in the wrists and fingers progressed more rapidly in the S/S group than in the S/N and N/N groups; and the rheumatoid susceptible alleles of HLA-DRB1 can be considered to be genetically recessive to the non-susceptible alleles in the progression of bone destructions in the wrists and fingers. CONCLUSION--Genotyping of HLA-DRB1 can be a useful prognostic marker in the early phase of RA.
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