No abstract

Objective. To investigate the dose tolerance and potential clinical activity of a humanized antilymphocyte monoclonal antibody, CAMPATH‐1H (C1H), in patients with active, refractory rheumatoid arthritis (RA). Methods. Thirty adult patients with active, refractory RA were treated in an open‐label, 3‐center, dose‐escalation study of subcutaneously injected C1H. Six patients were assigned to each of 5 dosage groups (0.3, 1.0, 3.0, 10.0 or 30.0 mg/day), and received 10 daily injections of C1H over a 12‐day period. Results. Side effects occurred primarily during the first 1–2 days of dosing, and included mild fever, chills, nausea, vomiting, headache, and, in a minority of patients, hypotension. All patients developed some discomfort at the injection site. Self‐limited infections occurred in 5 patients during the 6‐month study period. Peripheral blood lymphocyte counts fell promptly after initial dosing and recovered slowly, usually over 2–3 months. Serum antibodies to C1H developed in 54% of patients following treatment. Clinical improvement was observed in 56% of patients, based on the composite Paulus criteria, with a median time‐to‐response of 22 days and a median response duration of 32 days. Conclusion. C1H is a lymphocyte‐depleting antibody that exhibits biologic potency when administered subcutaneously to patients with refractory RA. Its use is associated with mild to moderate toxicity and short‐term amelioration of disease activity.

To determine the relative presence of TCR gamma delta+ and TCR alpha beta+ T cells in synovial tissue from patients with various types of inflammatory synovitis and in tissues from patients with a number of chronic T cell-mediated conditions, we stained frozen tissue sections with monoclonal antibodies in indirect immunofluorescence assays. In tissues obtained from patients with chronic T cell-mediated granulomatous conditions (Wegener's granulomatosis, lymphomatoid granulomatosis, granuloma annulare, Langerhans' cells granulomatosis, pigmented villonodular synovitis, Takayasu's arteritis, and talc granulomatosis), the T cells present were predominantly TCR alpha beta+, without an increased presence of TCR gamma delta+ cells. In contrast, 6 of 14 (43%) synovia from patients with rheumatoid arthritis (RA) showed increased TCR gamma delta+ T cells (3-10 cells/hpf). The RA synovia with increased TCR gamma delta+ cells present had an increased tissue inflammation score compared to RA synovia with few TCR gamma delta+ cells [18.6 +/- 5.8 versus 11.6 +/- 4.2 (mean +/- SE), P less than 0.05]. In contrast, synovia from patients with osteoarthritis, systemic lupus erythematosus, and trauma did not show an increased presence of TCR gamma delta+ T cells. Thus, in cellular inflammatory infiltrates the presence of increased TCR gamma delta cells is not a component of noninfectious granulomatous inflammation but is found in approximately 40% of RA synovia with high levels of inflammation.