Increase of peripheral CXCR3 positive T lymphocytes upon treatment of RA patients with TNF-α inhibitors

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 trea...

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Bibliographic Details
Published in:Rheumatology (Oxford, England) England), 2005-02, Vol.44 (2), p.172-175
Main Authors: Aeberli, D., Seitz, M., Jüni, P., Villiger, P. M.
Format: Article
Language:English
Subjects:
Adult
Aged
Antibodies, Monoclonal - therapeutic use
Antirheumatic Agents - therapeutic use
Arthritis, Rheumatoid - drug therapy
Arthritis, Rheumatoid - immunology
Biological and medical sciences
CD4-Positive T-Lymphocytes - immunology
CD8-Positive T-Lymphocytes - immunology
CXCR3
Disease activity score
Etanercept
Female
Humans
Immunoglobulin G - therapeutic use
Immunomodulators
Infliximab
Inhibition
Interferon-gamma - analysis
Interleukin-4 - analysis
Leukocyte Common Antigens - immunology
Male
Medical sciences
Middle Aged
Pharmacology. Drug treatments
Receptors, CCR4
Receptors, Chemokine - analysis
Receptors, Chemokine - immunology
Receptors, CXCR3
Receptors, Tumor Necrosis Factor - therapeutic use
T lymphocyte
T-Lymphocytes - immunology
Th1
TNF
Tumor Necrosis Factor-alpha - antagonists & inhibitors
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Summary: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.
ISSN:1462-0324
1462-0332
DOI:10.1093/rheumatology/keh437