RHEUMATOID-SUSCEPTIBLE ALLELES OF HLA-DRB1 ARE GENETICALLY RECESSIVE TO NON-SUSCEPTIBLE ALLELES IN THE PROGRESSION OF BONE DESTRUCTION IN THE WRISTS AND FINGERS OF PATIENTS WITH RA

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 radiographic 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 SIS 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 SIS group, 22.7 in the S/N group and 23.0 in the N/N group. The difference observed and S/N group, and 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 SIS 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.