Advances in immunotherapy of rheumatoid arthritis: clinical and immunological findings following treatment with anti-CD4 antibodies.
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.(ABSTRACT TRUNCATED AT 250 WORDS)
Horneff
G
G
Department of Paediatrics, University of Düsseldorf, Germany.
Emmrich
F
F
Burmester
G R
GR
D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000276:immunology / Q000628:therapy*; D001799:Blood Sedimentation; D002097:C-Reactive Protein / Q000032:analysis; D017252:CD3 Complex / Q000097:blood / Q000187:drug effects; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D016207:Cytokines / Q000097:blood / Q000187:drug effects; D006801:Humans; D007262:Infusions, Intravenous; D007958:Leukocyte Count / Q000187:drug effects; D008213:Lymphocyte Activation / Q000187:drug effects; D009000:Monocytes / Q000187:drug effects; D010865:Pilot Projects; D012720:Severity of Illness Index
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D016207:Cytokines; D002097:C-Reactive Protein