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Rheumatology International

, Volume 31, Issue 8, pp 1101–1103 | Cite as

Single high-dose treatment with glucosaminyl-muramyl dipeptide is ineffective in treating ankylosing spondylitis

  • Olga V. Britanova
  • Dmitriy B. Staroverov
  • Anna V. Chkalina
  • Alexei A. Kotlobay
  • Ekaterina S. Zvezdova
  • Anna G. Bochkova
  • Dmitriy M. ChudakovEmail author
Short Communication

Abstract

Earlier studies have shown that high doses of TNF-alpha increase apoptosis in human autoimmune T-cell clones. Based on these studies, a treatment approach was proposed to reduce or eliminate autoimmune T cells in patients with type 1 diabetes using drugs that temporarily elevate TNF levels. Here, we report the treatment of ankylosing spondylitis patient with a single high oral dose of Likopid (glucosaminyl-muramyl dipeptide), which aimed at increasing the levels of TNF-alpha in order to induce apoptosis of autoreactive T cells. The flow cytometric analysis of blood samples collected before and after treatment demonstrated massive elimination of CD8+ T cells. However, the treatment did not result in any notable therapeutic effect, and real-time PCR analysis demonstrated that stably expanded T-cell clones that were earlier tracked in this patient were unaffected. This report suggests that the controversial approach to eliminate autoimmune T-cell clones through overstimulation is not effective in treating ankylosing spondylitis.

Keywords

Autoimmune T cells TNF-alpha level Likopid Muramyl dipeptide NOD2 receptor Ankylosing spondylitis 

Notes

Acknowledgments

This work was supported by Molecular and Cell Biology program RAS, Rosnauka [02.512.12.2053]; and State Support of the Leading Scientific Schools [NS-5638.2010.4].

Conflict of interest

None.

References

  1. 1.
    De Keyser F, Van den Bosch F, Mielants H (2006) Anti-TNF-alpha therapy in ankylosing spondylitis. Cytokine 33:294–298PubMedCrossRefGoogle Scholar
  2. 2.
    Braun J, Baraliakos X (2009) Treatment of ankylosing spondylitis and other spondyloarthritides. Curr Opin Rheumatol 21:324–334PubMedCrossRefGoogle Scholar
  3. 3.
    Beg AA, Baltimore D (1996) An essential role for NF-kappaB in preventing TNF-alpha-induced cell death. Science 274:782–784PubMedCrossRefGoogle Scholar
  4. 4.
    Varfolomeev EE, Ashkenazi A (2004) Tumor necrosis factor: an apoptosis junkie? Cell 116:491–497PubMedCrossRefGoogle Scholar
  5. 5.
    Baetu TM, Kwon H, Sharma S, Grandvaux N, Hiscott J (2001) Disruption of NF-kappaB signaling reveals a novel role for NF-kappaB in the regulation of TNF-related apoptosis-inducing ligand expression. J Immunol 167:3164–3173PubMedGoogle Scholar
  6. 6.
    Ban L, Zhang J, Wang L, Kuhtreiber W, Burger D, Faustman DL (2008) Selective death of autoreactive T cells in human diabetes by TNF or TNF receptor 2 agonism. Proc Natl Acad Sci USA 105:13644–13649PubMedCrossRefGoogle Scholar
  7. 7.
    Faustman DL, Davis M (2009) The primacy of CD8 T lymphocytes in type 1 diabetes and implications for therapies. J Mol Med 87:1173–1178PubMedCrossRefGoogle Scholar
  8. 8.
    Coulombe F, Divangahi M, Veyrier F et al (2009) Increased NOD2-mediated recognition of N-glycolyl muramyl dipeptide. J Exp Med 206:1709–1716PubMedCrossRefGoogle Scholar
  9. 9.
    Farram E (1996) Profile of peptide technology Ltd Australasian Biotechnology 6:223–229Google Scholar
  10. 10.
    Mamedov IZ, Britanova OV, Chkalina AV et al (2009) Individual characterization of stably expanded T cell clones in ankylosing spondylitis patients. Autoimmunity 42:525–536PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Olga V. Britanova
    • 1
  • Dmitriy B. Staroverov
    • 1
  • Anna V. Chkalina
    • 1
  • Alexei A. Kotlobay
    • 1
  • Ekaterina S. Zvezdova
    • 1
  • Anna G. Bochkova
    • 2
  • Dmitriy M. Chudakov
    • 1
    Email author
  1. 1.Shemiakin-Ovchinnikov Institute of Bioorganic ChemistryRASMoscowRussia
  2. 2.Institute of RheumatologyRAMSMoscowRussia

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