title: Specific Depletion of Myelin-Reactive B Cells via BCR-Targeting.
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.
authors.affiliation: M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, Miklukho-Maklaya Str., 16/10, Russian Academy of Sciences, 117997, Moscow, Russia ; Kazan Federal University, Kremlevskaya Str., 18, 420008, Kazan, Republic of Tatarstan, Russia.
authors.forename: A V
authors.initials: AV
authors.lastname: Stepanov
authors.affiliation: M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, Miklukho-Maklaya Str., 16/10, Russian Academy of Sciences, 117997, Moscow, Russia ; Kazan Federal University, Kremlevskaya Str., 18, 420008, Kazan, Republic of Tatarstan, Russia ; Institute of Gene Biology, Russian Academy of Sciences, Vavilova Str., 34/5, 119334, Moscow, Russia.
authors.forename: A A
authors.initials: AA
authors.lastname: Belogurov
authors.affiliation: Centre de Recherche des Cordeliers, Université Pierre et Marie Curie, UMR S 1138, F-75006, Paris, France.
authors.forename: P
authors.initials: P
authors.lastname: Kothapalli
authors.affiliation: M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, Miklukho-Maklaya Str., 16/10, Russian Academy of Sciences, 117997, Moscow, Russia.
authors.forename: O G
authors.initials: OG
authors.lastname: Shamborant
authors.affiliation: M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, Miklukho-Maklaya Str., 16/10, Russian Academy of Sciences, 117997, Moscow, Russia.
authors.forename: V D
authors.initials: VD
authors.lastname: Knorre
authors.affiliation: M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, Miklukho-Maklaya Str., 16/10, Russian Academy of Sciences, 117997, Moscow, Russia.
authors.forename: G B
authors.initials: GB
authors.lastname: Telegin
authors.affiliation: M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, Miklukho-Maklaya Str., 16/10, Russian Academy of Sciences, 117997, Moscow, Russia.
authors.forename: A A
authors.initials: AA
authors.lastname: Ovsepyan
authors.affiliation: M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, Miklukho-Maklaya Str., 16/10, Russian Academy of Sciences, 117997, Moscow, Russia.
authors.forename: N A
authors.initials: NA
authors.lastname: Ponomarenko
authors.affiliation: M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, Miklukho-Maklaya Str., 16/10, Russian Academy of Sciences, 117997, Moscow, Russia.
authors.forename: S M
authors.initials: SM
authors.lastname: Deyev
authors.affiliation: Centre de Recherche des Cordeliers, Université Pierre et Marie Curie, UMR S 1138, F-75006, Paris, France.
authors.forename: S V
authors.initials: SV
authors.lastname: Kaveri
authors.affiliation: M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, Miklukho-Maklaya Str., 16/10, Russian Academy of Sciences, 117997, Moscow, Russia ; Kazan Federal University, Kremlevskaya Str., 18, 420008, Kazan, Republic of Tatarstan, Russia ; Institute of Gene Biology, Russian Academy of Sciences, Vavilova Str., 34/5, 119334, Moscow, Russia.
authors.forename: A G
authors.initials: AG
authors.lastname: Gabibov
keywords: B cells; autoantigens; immunoglobulins; immunotoxins; multiple sclerosis