PMID- 21816022 OWN - NLM STAT- MEDLINE DCOM- 20111201 LR - 20151119 IS - 1756-185X (Electronic) IS - 1756-1841 (Linking) VI - 14 IP - 3 DP - 2011 Aug TI - Decrease of CD68 and MMP-3 expression in synovium by treatment of adalimumab for rheumatoid arthritis. PG - 261-6 LID - 10.1111/j.1756-185X.2011.01643.x [doi] AB - 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. CI - (c) 2011 The Authors. International Journal of Rheumatic Diseases (c) 2011 Asia Pacific League of Associations for Rheumatology and Blackwell Publishing Asia Pty Ltd. FAU - Kanbe, Katsuaki AU - Kanbe K AD - Department of Orthopaedic Surgery, Tokyo Women's Medical University, Medical Center East, Tokyo, Japan. kanbeor@dnh.twmu.ac.jp FAU - Chiba, Junji AU - Chiba J FAU - Nakamura, Atsushi AU - Nakamura A LA - eng PT - Comparative Study PT - Journal Article PL - England TA - Int J Rheum Dis JT - International journal of rheumatic diseases JID - 101474930 RN - 0 (Antibodies, Monoclonal, Humanized) RN - 0 (Antigens, CD) RN - 0 (Antigens, Differentiation, Myelomonocytic) RN - 0 (Antirheumatic Agents) RN - 0 (CD68 antigen, human) RN - EC 3.4.24.17 (Matrix Metalloproteinase 3) RN - FYS6T7F842 (Adalimumab) RN - YL5FZ2Y5U1 (Methotrexate) SB - IM MH - Adalimumab MH - Aged MH - Antibodies, Monoclonal, Humanized/*therapeutic use MH - Antigens, CD/*metabolism MH - Antigens, Differentiation, Myelomonocytic/*metabolism MH - Antirheumatic Agents/*therapeutic use MH - Arthritis, Rheumatoid/*drug therapy/metabolism/pathology MH - Cell Proliferation MH - Drug Therapy, Combination MH - Female MH - Humans MH - Immunohistochemistry MH - Male MH - Matrix Metalloproteinase 3/*metabolism MH - Methotrexate/therapeutic use MH - Middle Aged MH - Synovial Membrane/blood supply/*drug effects/metabolism/pathology EDAT- 2011/08/06 06:00 MHDA- 2011/12/13 00:00 CRDT- 2011/08/06 06:00 PHST- 2011/08/06 06:00 [entrez] PHST- 2011/08/06 06:00 [pubmed] PHST- 2011/12/13 00:00 [medline] AID - 10.1111/j.1756-185X.2011.01643.x [doi] PST - ppublish SO - Int J Rheum Dis. 2011 Aug;14(3):261-6. doi: 10.1111/j.1756-185X.2011.01643.x.