Cargando…

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

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Stepanov, A. V., Belogurov Jr., 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: A.I. Gordeyev 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4463415/
https://www.ncbi.nlm.nih.gov/pubmed/26085947
_version_ 1782375765800648704
author Stepanov, A. V.
Belogurov Jr., 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.
author_facet Stepanov, A. V.
Belogurov Jr., 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.
author_sort Stepanov, A. V.
collection PubMed
description 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.
format Online
Article
Text
id pubmed-4463415
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher A.I. Gordeyev
record_format MEDLINE/PubMed
spelling pubmed-44634152015-06-17 Specific Depletion of Myelin-Reactive B Cells via BCR-Targeting Stepanov, A. V. Belogurov Jr., 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. Acta Naturae Research Article 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.I. Gordeyev 2015 /pmc/articles/PMC4463415/ /pubmed/26085947 Text en Copyright ® 2015 Park-media Ltd. http://creativecommons.org/licenses/by/2.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Stepanov, A. V.
Belogurov Jr., 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.
Specific Depletion of Myelin-Reactive B Cells via BCR-Targeting
title Specific Depletion of Myelin-Reactive B Cells via BCR-Targeting
title_full Specific Depletion of Myelin-Reactive B Cells via BCR-Targeting
title_fullStr Specific Depletion of Myelin-Reactive B Cells via BCR-Targeting
title_full_unstemmed Specific Depletion of Myelin-Reactive B Cells via BCR-Targeting
title_short Specific Depletion of Myelin-Reactive B Cells via BCR-Targeting
title_sort specific depletion of myelin-reactive b cells via bcr-targeting
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4463415/
https://www.ncbi.nlm.nih.gov/pubmed/26085947
work_keys_str_mv AT stepanovav specificdepletionofmyelinreactivebcellsviabcrtargeting
AT belogurovjraa specificdepletionofmyelinreactivebcellsviabcrtargeting
AT kothapallip specificdepletionofmyelinreactivebcellsviabcrtargeting
AT shamborantog specificdepletionofmyelinreactivebcellsviabcrtargeting
AT knorrevd specificdepletionofmyelinreactivebcellsviabcrtargeting
AT telegingb specificdepletionofmyelinreactivebcellsviabcrtargeting
AT ovsepyanaa specificdepletionofmyelinreactivebcellsviabcrtargeting
AT ponomarenkona specificdepletionofmyelinreactivebcellsviabcrtargeting
AT deyevsm specificdepletionofmyelinreactivebcellsviabcrtargeting
AT kaverisv specificdepletionofmyelinreactivebcellsviabcrtargeting
AT gabibovag specificdepletionofmyelinreactivebcellsviabcrtargeting