title: Autoantibodies to myelin basic protein catalyze site-specific degradation of their antigen.
abstract: Autoantibody-mediated tissue destruction is among the main features of organ-specific autoimmunity. This report describes "an antibody enzyme" (abzyme) contribution to the site-specific degradation of a neural antigen. We detected proteolytic activity toward myelin basic protein (MBP) in the fraction of antibodies purified from the sera of humans with multiple sclerosis (MS) and mice with induced experimental allergic encephalomyelitis. Chromatography and zymography data demonstrated that the proteolytic activity of this preparation was exclusively associated with the antibodies. No activity was found in the IgG fraction of healthy donors. The human and murine abzymes efficiently cleaved MBP but not other protein substrates tested. The sites of MBP cleavage determined by mass spectrometry were localized within immunodominant regions of MBP. The abzymes could also cleave recombinant substrates containing encephalytogenic MBP(85-101) peptide. An established MS therapeutic Copaxone appeared to be a specific abzyme inhibitor. Thus, the discovered epitope-specific antibody-mediated degradation of MBP suggests a mechanistic explanation of the slow development of neurodegeneration associated with MS.
authors.affiliation: Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 16/10, Miklukho-Maklaya Street, Moscow 117997, Russia.
authors.forename: Natalia A
authors.initials: NA
authors.lastname: Ponomarenko
authors.forename: Oxana M
authors.initials: OM
authors.lastname: Durova
authors.forename: Ivan I
authors.initials: II
authors.lastname: Vorobiev
authors.forename: Alexey A
authors.initials: AA
authors.lastname: Belogurov
authors.forename: Inna N
authors.initials: IN
authors.lastname: Kurkova
authors.forename: Alexander G
authors.initials: AG
authors.lastname: Petrenko
authors.forename: Georgy B
authors.initials: GB
authors.lastname: Telegin
authors.forename: Sergey V
authors.initials: SV
authors.lastname: Suchkov
authors.forename: Sergey L
authors.initials: SL
authors.lastname: Kiselev
authors.forename: Maria A
authors.initials: MA
authors.lastname: Lagarkova
authors.forename: Vadim M
authors.initials: VM
authors.lastname: Govorun
authors.forename: Marina V
authors.initials: MV
authors.lastname: Serebryakova
authors.forename: Bérangère
authors.initials: B
authors.lastname: Avalle
authors.forename: Pete
authors.initials: P
authors.lastname: Tornatore
authors.forename: Alexander
authors.initials: A
authors.lastname: Karavanov
authors.forename: Herbert C
authors.initials: HC
authors.lastname: Morse
authors.forename: Daniel
authors.initials: D
authors.lastname: Thomas
authors.forename: Alain
authors.initials: A
authors.lastname: Friboulet
authors.forename: Alexander G
authors.initials: AG
authors.lastname: Gabibov
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000941:Antigens / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism*; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D020134:Catalytic Domain; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology; D006801:Humans; D013058:Mass Spectrometry; D051379:Mice; D008810:Mice, Inbred C57BL; D009103:Multiple Sclerosis / Q000276:immunology / Q000473:pathology; D004676:Myelin Basic Protein / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: D000941:Antigens; D001323:Autoantibodies; D004676:Myelin Basic Protein