© 1993 British Society for Rheumatology
Advances in Immunotherapy of Rheumatoid Arthritis: Clinical and Immunological Findings Following Treatment with Anti-CD4 Antibodies
* Department of Paediatrics, University of Düsseldorf
Max-Planck-Clinical Research Group, University of Erlangen-Nuremberg
Department of Medicine III, University of Erlangen-Nuremberg Düsseldorf Germany
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Abstract |
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Rheumatoid arthritis is a chronic inflammatory disease mainly affecting the joints. The etiology of the disease is still unknown, but it shows several of the clinical and laboratory features of an autoimmune process. Often, efficacy of conventional treatment is not satisfactory in patients with RA and therefore, alternative therapies have to be considered. Since CD4+ T helper cells appear to play an important role in disease pathogenesis, anti-CD4 treatment has been tried in RA patients. This paper will present a summary of our experience including some new recent findings upon immunomodulation caused by anti-CD4. Following anti-CD4 antibody infusion with antibody MAX16H5, a decline in lymphocyte counts has been observed with a depletion of CD3+ T cells to 30%, CD4 + T cells to 13% and monocytes to 33% of pretreatment levels. Moreover, all remaining T helper cells were coated by anti-CD4. No changes in CD8+ T cells or B lymphocytes were noted. After a partial recovery of CD4+ T cells, decreased numbers were maintained for 8 weeks. Modulation of the target antigen was demonstrated by high levels of soluble CD4 and a decreased CD4 antigen density on T helper cells down to 30% of the original level, which reached pretreatment levels 2 weeks after therapy. Proliferative responses to mitogens and antigens were reduced immediately after the antibody infusions but were markedly increased in some patients when compared to the pretreatment situation. In addition, a rapid decrease of monocyte/macrophage activation markers was observed. Clinical improvement occurred during treatment and resulted in a decreased Ritchie articular index, numbers of swollen joints and a shortening or loss of morning stiffness as well as an increase in grip strength and functional abilities. It was accompanied by a significant decrease in the ESR, CRP, RF as well as serum levels of cytokines and in vitro cytokine production. No major side effects were observed. Together, the encouraging clinical and immunological data observed in this pilot study would support further evaluation of anti-CD4 therapy in RA and the design of controlled studies also including repeated treatment.
KEY WORDS: Rheumatoid arthritis, CD4 antigens, Monoclonal antibody therapy
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