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OBJECTIVE: Adenosine exerts antiinflammatory effects via activation of the A3 adenosine receptor (A3AR), a Gi protein-associated cell-surface receptor, overexpressed in synovial tissue and peripheral blood mononuclear cells (PBMC) in patients with active rheumatoid arthritis (RA). CF101 is a highly specific orally bioavailable A3AR agonist. METHODS: This was a multicenter study, blinded to dose, designed to assess the clinical activity and safety of CF101 in active RA. Seventy-four patients were randomized to receive 0.1, 1.0, or 4.0 mg CF101 bid for 12 weeks. The primary efficacy endpoint was American College of Rheumatology 20% response (ACR20) at Week 12. A3AR expression levels were analyzed in PBMC from 18 patients. RESULTS:. Maximal responses were observed with 1.0 mg bid, lower at 0.1 and 4.0 mg bid. At 12 weeks, 55.6%, 33.3%, and 11.5% of the patients receiving 1.0 mg CF101 achieved ACR20%, 50%, and 70% responses, respectively. CF101 was generally well tolerated, with mild headache (4.1%), nausea (2.7%), and rash (2.7%) being the most common treatment-related adverse events. Statistically significant correlations between A3AR overexpression at baseline and ACR50 and ACR70 responses were observed. CONCLUSION: CF101 administered bid for 12 weeks resulted in improvement in signs and symptoms of RA that did not achieve statistical significance, and was safe and well tolerated. The expression level of A3AR was directly correlated with patient responses to CF101, suggesting its utilization as a biomarker for the pharmacodynamic and therapeutic effects of this novel agent. These findings require confirmation in a double-blind randomized placebo-controlled trial, currently under way.

Expanded populations of T lymphocytes bearing γδ T cell receptors have been detected in several patients with Felty syndrome. The goal of this study was to functionally characterize these lymphocytes in a newly described patient with this disease. For this, fluorescence-activated cell sorter analysis of T cell surface antigens, proliferation, and tumor necrosis factor α enzyme-linked immunosorbent assays, as well as quantitative assays of immunoglobulins secreted by pokeweed mitogen-driven B cells were performed. The γδ cells, that expressed a CD3⁺CD4^-Vγ9^-Vδ2⁺Cδ⁺ phenotype, and constituted 60% of the peripheral blood T cells, did not proliferate after triggering with anti-CD3, but did secrete tumor necrosis factor α and the addition of these cells to pokeweed mitogen-stimulated B cells from the patient decreased their secretion of immunoglobulin M while augmenting IgG secretion. These data suggest that the expanded anergic Vγ9^-Vδ2⁺ γδ cells can play an immunoregulatory role in the patient. Copyright 1995, 1999 Academic Press