Increased peripheral T cell reactivity to microbial antigens and collagen type II in rheumatoid arthritis after treatment with soluble TNF alpha receptors

Objective-Peripheral T cells from patients with rheumatoid arthritis (RA) are hyporesponsive when stimulated with antigen or mitogen in vitro, possibly owing to increased production of proinflammatory cytokines such as tumour necrosis factor alpha (TNF alpha). This study sought to find out if and how RA T eel reactivity is affected during treatment with etanercept (Enbrel), a soluble TNF alpha receptor, Methods-Heparinised blood was collected from patients with RA at baseline, after four and eight weeks of etanercept treatment, and from healthy controls. After density separation spontaneous production of interferon gamma (IFN gamma), TNF alpha, interleukin 6 (IL6), and IL10 by peripheral blood mononuclear cells (PBMC) was detected by ELISPOT. For detection of T cell reactivity, PBMC were stimulated in vitro with mitogen (phytohaemagglutinin (PHA)), microbial antigens (purified protein derivative (PPD), influenza), or an autoantigen, collagen type II (CII). Supernatants were analysed for IFN gamma and IL2 content by enzyme linked immunosorbent assay (ELISA). Results-In RA the number of cells spontaneously producing IFN gamma was significantly increased after four, but not eight weeks' treatment with etanercept. T cell reactivity, as measured by IFN gamma production to PPD, influenza, and CII was significantly increased after four and sustained after eight weeks' treatment, whereas IFN I production induced by PHA remained unchanged. TNF alpha production was significantly higher in patients with RA than in controls and did not change during etanercept treatment. Conclusion-Treatment of patients with RA with etanercept may lead to increased peripheral T cell reactivity both to microbial antigens and to self antigens such as CII. These findings indicate that TNF alpha blockade may not only suppress but also stimulate certain aspects of antimicrobial immune defence and autoimmunity