Specific Depletion of Myelin-Reactive B Cells via BCR-Targeting

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  • Authors: Stepanov A.V.1,2, Belogurov A.A.1,2,3, Kothapalli P.4, Shamborant O.G.1, Knorre V.D.1, Telegin G.B.1, Ovsepyan A.A.1, Ponomarenko N.A1, Deyev S.M.1, Kaveri S.V.4, Gabibov A.G.1,2,3
  • Affiliations:
    1. M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry
    2. Kazan Federal University
    3. Institute of Gene Biology, Russian Academy of Sciences
    4. Centre de Recherche des Cordeliers, Université Pierre et Marie Curie
  • Issue: Vol 7, No 2 (2015)
  • Pages: 74-79
  • Section: Research Articles
  • URL: http://actanaturae.ru/2075-8251/article/view/10502
  • DOI: https://doi.org/10.32607/20758251-2015-7-2-74-79
  • Cite item

Abstract


B cells play a crucial role in the development and pathogenesis of systemic and organ-specific autoimmune diseases. Autoreactive B cells not only produce antibodies, but also secrete pro-inflammatory cytokines and present specific autoantigens to T cells. The treatment of autoimmune diseases via the elimination of the majority of B cells using the monoclonal anti-CD19/20 antibody (Rituximab) causes systemic side effects and, thus, requires a major revision. Therapeutic intervention directed towards selective elimination of pathogenic autoreactive B cells has the potential to become a universal approach to the treatment of various autoimmune abnormalities. Here, we developed a recombinant immunotoxin based on the immunodominant peptide of the myelin basic protein (MBP), fused to the antibody Fc domain. We showed that the obtained immunotoxin provides selective in vivo elimination of autoreactive B cells in mice with experimental autoimmune encephalomyelitis. The proposed conception may be further used for the development of new therapeutics for a targeted treatment of multiple sclerosis and other autoimmune disorders.


A. V. Stepanov

M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry; Kazan Federal University

Author for correspondence.
Email: stepanov.aleksei.v@gmail.com

Russian Federation

A. A. Belogurov

M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry; Kazan Federal University; Institute of Gene Biology, Russian Academy of Sciences

Email: stepanov.aleksei.v@gmail.com

Russian Federation

P. Kothapalli

Centre de Recherche des Cordeliers, Université Pierre et Marie Curie

Email: stepanov.aleksei.v@gmail.com

France

O. G. Shamborant

M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry

Email: stepanov.aleksei.v@gmail.com

Russian Federation

V. D. Knorre

M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry

Email: stepanov.aleksei.v@gmail.com

Russian Federation

G. B. Telegin

M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry

Email: stepanov.aleksei.v@gmail.com

Russian Federation

A. A. Ovsepyan

M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry

Email: stepanov.aleksei.v@gmail.com

Russian Federation

N. A Ponomarenko

M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry

Email: stepanov.aleksei.v@gmail.com

Russian Federation

S. M. Deyev

M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry

Email: stepanov.aleksei.v@gmail.com

Russian Federation

S. V. Kaveri

Centre de Recherche des Cordeliers, Université Pierre et Marie Curie

Email: stepanov.aleksei.v@gmail.com

France

A. G. Gabibov

M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry; Kazan Federal University; Institute of Gene Biology, Russian Academy of Sciences

Email: stepanov.aleksei.v@gmail.com

Russian Federation

  1. Nylander A., Hafler D.A. // J. Clin. Invest. 2012. V. 122. P. 1180-1188.
  2. Kingwell E., Marriott J.J., Jette N., Pringsheim T., Makhani N., Morrow S.A., Fisk J.D., Evans C., Beland S.G., Kulaga S. // BMC Neurol. 2013. V. 13. P. 128.
  3. Ransohoff R.M., Hafler D.A., Lucchinetti C.F. // Nat. Rev. Neurol. 2015. V. 11. P. 134-142.
  4. Sorensen P.S. // Curr. Opin. Neurol. 2014. V. 27. P. 246-259.
  5. Krumbholz M., Derfuss T., Hohlfeld R., Meinl E. // Nat. Rev. Neurol. 2012. V. 8. P. 613-623.
  6. Marino E., Grey S.T. // Autoimmunity. 2012. V. 45. P. 377-387.
  7. Arkfeld D.G. // Rheumatol. Int. 2008. V. 28. P. 205-215.
  8. Wang M., Fowler N., Wagner-Bartak N., Feng L., Romaguera J., Neelapu S.S., Hagemeister F., Fanale M., Oki Y., Pro B. // Leukemia. 2013. V. 27. P. 1902-1909.
  9. Ransohoff R.M., Zamvil S.S. // Neurotherapeutics. 2007. V. 4. P. 569-570.
  10. Cross A.H., Stark J.L., Lauber J., Ramsbottom M.J., Lyons J.A. // J. Neuroimmunol. 2006. V. 180. P. 63-70.
  11. Deyev S.M., Lebedenko E.N. // Acta Naturae. 2009. No. 1. P. 32-50.
  12. Deyev S.M., Lebedenko E.N., Petrovskaya L.E., Dolgikh D.A., Gabibov A.G., Kirpichnikov M.P. // Russian chemical reviews. 2015. V. 84. No. 1. P. 1-26.
  13. Castillo-Trivino T., Braithwaite D., Bacchetti P., Waubant E. // PLoS One. 2013. V. 8. P. e66308.
  14. Sela M., Mozes E. // Proc. Natl. Acad. Sci. USA. 2004. V. 101. P. 14586-14592.
  15. Stepanov A.V., Belogurov A.A. Jr., Ponomarenko N.A., Stremovskiy O.A., Kozlov L.V., Bichucher A.M., Dmitriev S.E., Smirnov I.V., Shamborant O.G., Balabashin D.S., et al. // PLoS One. 2011. V. 6 (6). P. e20991.
  16. Zocher M., Baeuerle PA, Dreier T., Iglesias A. // Int Immunol. 2003. V.15 (7). P. 789-796.
  17. Johnson A.B., Dal Canto M.C. // Nature. 1976. V. 264. P. 453-454.
  18. Abramsky O., Lisak R.P., Silberberg D.H., Pleasure D.E. // New Engl. J. Med. 1978. V. 298. P. 743.
  19. Ponomarenko N.A., Durova O.M., Vorobiev I.I., Belogurov A.A. Jr., Kurkova I.N., Petrenko A.G., Telegin G.B., Suchkov S.V., Kiselev S.L., Lagarkova M.A., et al. // Proc. Natl. Acad. Sci. USA. 2006. V. 103. № 2. P. 281-286.
  20. Miller S.D., Karpus W.J., Davidson T.S. // Curr. Protoc. Immunol. 2010. Ch. 15. V. 15. P. 11.
  21. Stromnes I.M., Goverman J.M. // Nat. Protoc. 2006. V. 1. P. 1810-1819.
  22. Belogurov A.A. Jr., Kurkova I.N., Friboulet A., Thomas D., Misikov V.K., Zakharova M.Y., Suchkov S.V., Kotov S.V., Alehin A.I., Avalle B., et al. // J. Immunol. 2008. V. 180. P. 1258-1267.
  23. Yasuda T., Tsumita T., Nagai Y., Mitsuzawa E., Ohtani S. // Japan J. Exp. Med. 1975. V. 45. P. 423-427.
  24. Sela M., Teitelbaum D. // Expert Opin. Pharmacother. 2001. V. 2. P. 1149-1165.

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Copyright (c) 2015 Stepanov A.V., Belogurov A.A., Kothapalli P., Shamborant O.G., Knorre V.D., Telegin G.B., Ovsepyan A.A., Ponomarenko N.A., Deyev S.M., Kaveri S.V., Gabibov A.G.

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