In addition, The percentage of peripheral CD4+DR3+T cells of RA was significantly higher than that of healthy controls (HC), and this increased percentage of CD4+DR3+T cells was obviously up-regulated when stimulated with anti-CD3 and anti-CD28 antibody in RA patients.
The CpG island in the DR3 gene promoter was specifically methylated to down-modulate the expression of DR-3 protein in rheumatoid synovial cells, which may provide resistance to apoptosis in RA synovial cells.
This may cause aberrations in either T cell function or in response of bone cells to DR3 ligands, which may contribute to pathology in rheumatoid arthritis.
The existence of the duplicated DR3 gene was confirmed by sequencing the corresponding human artificial chromosome clones as well as with quantitative PCR that measured the ratio of the DR3 gene mutation (Rm), intrinsic to rheumatoid arthritis (RA) patients, by simultaneous amplification of the normal and mutated DR3 sequences.