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

Aims: 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. Methods: 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-alpha (TNF-alpha), 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. Results: 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-alpha, 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. Conclusion: 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.