Decrease of CD68 and MMP-3 expression in synovium by treatment of adalimumab for rheumatoid arthritis

Abstract

In order to investigate the histological change in the secondary non-responder cases of adalimumab compared with methotrexate (MTX) treatment, we performed immunohistochemical examination of synovial tissue by seven different molecules to detect expression patterns of cytokines. We histologically assessed synovial tissues from five MTX-treated rheumatoid arthritis (RA) patients as controls and five adalimumab plus MTX-treated RA patients after arthroscopic synovectomy in the knee joints. The synovium of both groups were assessed by hematoxylin and eosin (H&E) and analyzed the positive expression of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), matrix metalloproteinase-3 (MMP-3), B-cell precursor and mature B-cell transmembrane protein, CD20, macrophage marker, CD68, vascular endothelial growth factor (VEGF), receptor activator of nuclear (kappa) B ligand (RANKL) by immunohistochemical examination. H&E staining showed the increase of vascular and cell proliferations in the synovium of the RA patients who received adalimumab compared with the controls. TNF-α, IL-6 and CD20 were not significantly different in either group. On the other hand, MMP-3 and CD68 showed a significant decrease in the adalimumab group compared with controls (P < 0.05). VEGF and RANKL were weakly positive in both groups. Based on the histological analysis of synovium, the effect attenuation of adalimumab may be involved in vascular and cell proliferations; however, there was inhibition of the expression of CD68 and MMP-3 in synovium. These findings indicate CD68 and MMP-3 may have key roles in the mechanism of efficacy of adalimumab.