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Clonal expansions in selected TCR BV families of rheumatoid arthritis patients are reduced by treatment with the TNFα inhibitors etanercept and infliximab

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Abstract

Clonal expansions of autoreactive CD4+ T cells are frequently present in patients with rheumatoid arthritis (RA) and are stable over long periods of time. This study was undertaken to investigate the influence of anti-TNFα treatment on such clonal expansions in the peripheral CD4+ T-cell compartment. TNFα inhibiting therapies significantly reduced the total number of expanded clonotypes. This effect was mainly observed in clonal expansions in the BV6 family, while in clonal expansions of the BV14 family no such effect was seen. No change in the percentage of CD4+ CD28 null T cells was observed. Serum concentrations of the pro-homeostatic cytokine IL-7 were found to increase in patients responding TNFα-inhibiting therapy. These data argue for a normalization of adaptive immune mechanisms under TNFα inhibiting therapies, which may be secondary to the control of inflammation but contribute to the efficacy of cytokine blockade therapy.

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Abbreviations

TNF α:

Tumor necrosis factor α

CDR3:

Complementarity determining region 3

RA:

Rheumatoid arthritis

TCR:

T-cell receptor

IL-7:

Interleukin 7

CMV:

Cytomegalovirus

BV:

Variable region of the T-cell receptor beta chain

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Acknowledgments

The work presented here was supported by grants from the German Ministry for Education and Science (Interdisziplinäres Zentrum für Klinische Forschung Leipzig, Teilprojekt A 15 and the Kompetenznetzwerk Rheuma, Entzündlich-rheumatische Systemerkrankungen, Teilprojekt C2.7).

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The author(s) declare that they have no competing interests.

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Authors and Affiliations

  1. Department of Medicine II, University of Leipzig, Johannisallee 30, 04103, Leipzig, Germany

    Matthias Pierer, Manuela Rossol, Sylke Kaltenhäuser, Sybille Arnold, Holm Häntzschel, Christoph Baerwald & Ulf Wagner

  2. Department of Medicine II, University of Leipzig, Liebigstrasse 22, 04103, Leipzig, Germany

    Matthias Pierer

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  1. Matthias Pierer
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  2. Manuela Rossol
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  3. Sylke Kaltenhäuser
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  4. Sybille Arnold
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  5. Holm Häntzschel
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  6. Christoph Baerwald
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  7. Ulf Wagner
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Correspondence to Matthias Pierer.

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Pierer, M., Rossol, M., Kaltenhäuser, S. et al. Clonal expansions in selected TCR BV families of rheumatoid arthritis patients are reduced by treatment with the TNFα inhibitors etanercept and infliximab. Rheumatol Int 31, 1023–1029 (2011). https://doi.org/10.1007/s00296-010-1402-9

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  • DOI: https://doi.org/10.1007/s00296-010-1402-9

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