Histological analysis of synovium by treatment of etanercept for rheumatoid arthritis

Int J Rheum Dis. 2009 Apr;12(1):7-13. doi: 10.1111/j.1756-185X.2009.01372.x.

Abstract

Aims: In order to investigate the histological change in effect attenuation cases of etanercept compared with methotrexate (MTX), we performed immunohistochemical examination by seven different molecules.

Methods: We histologically assessed synovial tissue from five MTX-treated rheumatoid arthritis (RA) patients as control and six etanercept and MTX-treated RA patients after synovectomy by arthroscopy. The synovium of both groups were assessed by hematoxylin and eosin (HE) and we also analysed the expression of tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), matrix metalloproteinase-3 (MMP-3), B-cell precursors and mature B-cell transmembrane protein, CD20, macrophage marker, CD68, bromodeoxyuridine (BrdU) and vascular endothelial growth factor (VEGF) by immunohistochemistry.

Results: HE staining showed vascular and cell proliferations of the synovium of the RA patients who received etanercept compared with the control MTX group. TNF-alpha and IL-6 were expressed in both groups.MMP-3 and CD68 expressed less significantly in the etanercept group compared with the control (P < 0.05). CD20 strongly expressed in the etanercept group significantly (P < 0.05). BrdU expressed in the synovium in the etanercept group significantly (P < 0.05). VEGF was not found overall in both group.

Conclusion: Based on the histological change of synovium, treatment by etanercept may be involved in vascular and cell proliferations with inhibition of the expression of CD68 and MMP-3 in synovium of RA patients. These findings indicate immunohistochemical change of synovium with etanercept is one of the mechanism of efficacy of etanercept.

MeSH terms

  • Aged
  • Antigens, CD / metabolism
  • Antigens, Differentiation, Myelomonocytic / metabolism
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / metabolism
  • Arthritis, Rheumatoid / pathology
  • Biomarkers / metabolism
  • Etanercept
  • Female
  • Fluorescent Antibody Technique, Indirect
  • Humans
  • Immunoglobulin G / therapeutic use*
  • Interleukin-6 / metabolism
  • Male
  • Matrix Metalloproteinase 3 / metabolism
  • Methotrexate / therapeutic use*
  • Middle Aged
  • Receptors, Tumor Necrosis Factor / therapeutic use*
  • Synovial Membrane / drug effects*
  • Synovial Membrane / metabolism
  • Synovial Membrane / pathology
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • Antirheumatic Agents
  • Biomarkers
  • CD68 antigen, human
  • IL6 protein, human
  • Immunoglobulin G
  • Interleukin-6
  • Receptors, Tumor Necrosis Factor
  • Tumor Necrosis Factor-alpha
  • Matrix Metalloproteinase 3
  • Etanercept
  • Methotrexate