Reduction of Synovial Inflammation After anti-CD4 Monoclonal Antibody Treatment in Early Rheumatoid Arthritis

Arthritis Rheum. 1995 Oct;38(10):1457-65. doi: 10.1002/art.1780381012.

Abstract

Objective: To study the effect of chimeric anti-CD4 monoclonal antibody (MAb) therapy on synovial inflammation, in order to interpret the clinical experience with anti-CD4 treatment.

Methods: The immunohistologic features of synovial biopsy specimens before and 4 weeks after anti-CD4 MAb (cM-T412) therapy were studied in patients with rheumatoid arthritis. The patients received intravenous doses of either placebo (n = 1) or 10 mg (n = 4), 25 mg (n = 2), or 50 mg (n = 1) of cM-T412 daily for 5 consecutive days.

Results: Although the patients did not experience clinical improvement, significant decreases in the number of circulating CD4+ cells, the degree of synovial inflammatory infiltration, and the mean scores for expression of adhesion molecules were found in the 7 patients 4 weeks after receiving cM-T412. The scores for infiltration with CD4+ and other inflammatory cells were particularly reduced following treatment with either 25 mg or 50 mg cM-T412. Cytokines, such as interleukin-1 beta and tumor necrosis factor alpha, could still be detected in the synovial tissue after treatment.

Conclusion: The decline in the numbers of inflammatory cells and adhesion molecules in synovial tissue after CD4+ cell depletion supports the view that CD4+ T cells orchestrate local cellular infiltration. The lack of clinical effect of anti-CD4 therapy might be explained by an insufficient decrease in the number of synovial CD4+ cells and by the persistence of cytokines. Determination of whether more adequate dosing would lead to a clinical improvement must await further study.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal / therapeutic use*
  • Arthritis, Rheumatoid / complications
  • Arthritis, Rheumatoid / immunology
  • Arthritis, Rheumatoid / pathology
  • Arthritis, Rheumatoid / therapy*
  • CD4 Antigens / immunology*
  • CD4 Lymphocyte Count
  • Cytokines / analysis
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Middle Aged
  • Synovial Membrane / immunology
  • Synovial Membrane / pathology
  • Synovitis / immunology
  • Synovitis / pathology
  • Synovitis / prevention & control*
  • Time Factors

Substances

  • Antibodies, Monoclonal
  • CD4 Antigens
  • Cytokines