Increase of peripheral CXCR3 positive T lymphocytes upon treatment of RA patients with TNF-α inhibitors
Aeberli D., Seitz M., Jüni P., Villiger PM.
Objective. To explore the regulation of factors involved in lymphocyte trafficking in patients with rheumatoid arthritis (RA) undergoing treatment with tumour necrosis factor α (TNF-α) inhibitors. Methods. We examined 14 consecutive patients with RA according to ACR criteria prior to and during treatment with TNF-α inhibitors (seven etanercept, seven infliximab) and determined disease activity using the Disease Activity Score (DAS-28). Peripheral blood mononuclear cells were isolated before and after 6 and 14 weeks of treatment and analysed immediately for CD3, CD4 and CD8, expression of chemokine receptors CXCR3 and CCR4, CD45RO phenotype and for expression of interferon γ (IFN-γ) and interleukin 4 (IL-4) using four-colour flow cytometry. Results. We found significant increases in CD4 and CD8 T lymphocytes expressing CXCR3 after 6 and 14 weeks. The overall proportion of T lymphocytes expressing CCR4 appeared unchanged. More than half of peripheral CD4 T lymphocytes showed a memory phenotype (CD45RO), with a non-significant increase under TNF-α inhibition. Upon activation, up to 30% of CXCR3+/CD4 T cells expressed IFN-γ, while IL-4-expressing cells were rare. There was a robust negative correlation between CXCR3+/CD4 T lymphocytes and DAS-28. Conclusions. TNF-α inhibition with infliximab and etanercept results in sustained accumulation of CXCR3 positive T lymphocytes in the peripheral blood of RA patients. This suggests altered lymphocyte trafficking during TNF-α inhibition. © British Society for Rheumatology 2004; all rights reserved.