In Vitro Analysis of Proliferating CD4+ T Cells in Patients with Rheumatoid Arthritis as a Possible Predictable Marker of TNF-alpha Blockers

Objectives. To analyze the relationship between in vitro cytokine production in proliferating CD4+ T cells and the effect of anti-TNF-alpha (tumor necrosis factor-alpha) agents (TNF-alpha blockers) in patients with rheumatoid arthritis (RA). Methods. Peripheral blood mononuclear cells (PBMCs) from RA patients (n=19) were labeled with CFSE [5 (and 6) carboxyfluorescein diacetate, succinimidyl ester] and cultured with ConA. CD4+ T cells were assessed for production of IFN-gamma, IL-4 and TNF-alpha, and proliferation by flow cytometry. We examined association of these parameters with clinical response of TNF-alpha blockers in short, medium and long term studies. Results: Clinically good response of TNF-alpha blockers was associated with lower TNF-alpha production in proliferating CD4+ T cells in short term study (p<0.05). Increased production of IFN-gamma (p<0.05) in proliferating CD4+ T cells was associated with good response in long term study. Conclusions: In vitro evaluation of cytokine production in proliferating CD4+ T cells, prior to treatment of TNF-alpha blockers, may provide possible information of efficacy of TNF-alpha blockers in RA patients.