Histological analysis of synovium in cases of effect attenuation associated with infliximab therapy in rheumatoid arthritis.
To investigate the histological changes of synovium in cases of effect attenuation occurring after the use of infliximab in the treatment of rheumatoid arthritis (RA), we histologically assessed synovial tissue from ten methotrexate-treated RA patients and 12 infliximab-treated RA patients after arthroscopic synovectomy. The synovium was observed using hematoxylin and eosin (H&E) stain and analyzed immunohistochemically for expression of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), matrix metalloproteinase-3 (MMP-3), B-cell transmembrane protein, cluster of differentiation 20 (CD20), nuclear factor kappa B (NFkB), bromodeoxyuridine (BrdU), and vascular endothelial growth factor (VEGF). H&E staining showed significant vascular proliferation in the synovium of the RA patients in the infliximab group (p < 0.05). Immunohistochemical examinations showed that TNF-alpha was completely blocked in patients with effect attenuation who received infliximab (p < 0.05). IL-6 was more strongly expressed in the interstitial cells of synovium of patients who received infliximab than in the cells of patients in the control group (p < 0.05). MMP-3 was expressed on the surface of synovium, and CD20 and BrdU were strongly expressed in the infliximab group compared with the control group (p < 0.05). NFkB was expressed in both groups. VEGF was decreased in the infliximab group compared with control. These findings indicate that the expression pattern of immunohistochemical findings in synovium was changed in effect attenuation cases among RA patients treated with infliximab.
Kanbe
Katsuaki
K
Department of Orthopaedic Surgery, Tokyo Women's Medical University, Medical Center East, 2-1-10 Nishiogu, Arakawa, Tokyo 116-8567, Japan. kanbeor@dnh.twmu.ac.jp
Inoue
Kazuhiko
K
Inoue
Yasuo
Y
Suzuki
Yutaka
Y
D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D018951:Antigens, CD20 / Q000378:metabolism; D018501:Antirheumatic Agents / Q000008:administration & dosage*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000473:pathology*; D001973:Bromodeoxyuridine / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D000069285:Infliximab; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D013583:Synovial Membrane / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D000911:Antibodies, Monoclonal; D018951:Antigens, CD20; D018501:Antirheumatic Agents; C508600:IL6 protein, human; D015850:Interleukin-6; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000069285:Infliximab; D019278:Matrix Metalloproteinase 3; D001973:Bromodeoxyuridine; D008727:Methotrexate