Specific Depletion of Myelin-Reactive B Cells via BCR-Targeting
- 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
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Affiliations:
- M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry
- Kazan Federal University
- Institute of Gene Biology, Russian Academy of Sciences
- Centre de Recherche des Cordeliers, Université Pierre et Marie Curie
- Issue: Vol 7, No 2 (2015)
- Pages: 74-79
- Section: Research Articles
- URL: https://actanaturae.ru/2075-8251/article/view/10502
- DOI: https://doi.org/10.32607/20758251-2015-7-2-74-79
- ID: 10502
Cite item
Full Text
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.
Keywords
About the authors
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
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