Frequency of Regulatory T Cells is Not Affected by Transient B Cell Depletion Using Anti-CD20 Antibodies in Rheumatoid Arthritis



Martin Feuchtenberger*, 1, Sabine Müller1, Petra Roll1, Anne Waschbisch2, Arne Schäfer1, Christian Kneitz1, Heinz Wiendl2, Hans-Peter Tony1
1 University of Würzburg, Department of Medicine II, Rheumatology and Clinical Immunology, Germany
2 University of Würzburg, Department of Neurology, Germany


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© Feuchtenberger et al.; Licensee Bentham Open

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/), which permits unrestrictive use, distribution, and reproduction in any medium, provided the original work is properly cited.

* Address correspondence to this author at the University of Würzburg, Dept of Medicine II, Rheumatology and Clinical Immunology Klinikstraße 6, D-97070 Würzburg, Germany; Tel: +49-(0)931/201-0; Fax: +49-(0)931/201-70421; E-mail: feuchtenbe_m@klinik.uni-wuerzburg.de


Abstract

Objectives

Transient B cell depletion with the monoclonal anti-CD20 antibody rituximab has shown favourable clinical responses in patients with rheumatoid arthritis (RA). Recently a characteristic regeneration pattern of B cell subpopulations has been reported. However, little is known about the impact of B-cell depletion on peripheral T cells in particular regulatory T cells.

Materials and Methodology

17 patients with RA having failed anti-TNF were treated with rituximab. Four colour staining was performed using CD19, CD3, CD4, CD8, CD16, CD56, CD25, HLA-DR, HLA-G and intracellular Foxp3 at five time points spanning up to 12 months after rituximab. In addition, quantification of the soluble form of the HLA class I molecule HLA-G by ELISA has been performed.

Results

Peripheral B cell depletion lasted 6 to 9 months. The absolute number of CD3+, CD4+ and CD8+ lymphocytes showed no significant changes up to 1 year after B-cell depletion compared to before therapy. Only the relative frequency for CD3 and CD4 showed a significant increase (p < 0.05). In particular, CD4+CD25++ and Foxp3 positive regulatory T cells remained constant. The percentage of HLA-G positive cells in the CD4+ or CD8+ population did not change significantly either. The amount of sHLA-G remained without significant changes.

Conclusion

Absolute T cell counts showed no significant changes after rituximab compared to the time point before therapy.In particular, the frequency of regulatory T cells with a CD4+CD25++ phenotype as well as positive Foxp3 expression were numerically stable. Additionally, HLA-G positive regulatory T cells and soluble levels of HLA-G showed no significant changes.