Document Detail


Recognition and degradation of myelin basic protein peptides by serum autoantibodies: novel biomarker for multiple sclerosis.
MedLine Citation:
PMID:  18178866     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The pathologic role of autoantibodies in autoimmune disease is widely accepted. Recently, we reported that anti-myelin basic protein (MBP) serum Abs from multiple sclerosis (MS) patients exhibit proteolytic activity toward the autoantigen. The aim of this study is to determine MBP epitopes specific for the autoantibodies in MS and compare these data with those from other neuronal disorders (OND), leading to the generation of new diagnostic and prognostic criteria. We constructed a MBP-derived recombinant "epitope library" covering the entire molecule. We used ELISA and PAGE/surface-enhanced laser desorption/ionization mass spectroscopy assays to define the epitope binding/cleaving activities of autoantibodies isolated from the sera of 26 MS patients, 22 OND patients, and 11 healthy individuals. The levels of autoantibodies to MBP fragments 48-70 and 85-170 as well as to whole MBP and myelin oligodendrocyte glycoprotein molecules were significantly higher in the sera of MS patients than in those of healthy donors. In contrast, selective reactivity to the two MBP fragments 43-68 and 146-170 distinguished the OND and MS patients. Patients with MS (77% of progressive and 85% of relapsing-remitting) but only 9% of patients with OND and no healthy donors were positive for catalysis, showing pronounced epitope specificity to the encephalitogenic MBP peptide 81-103. This peptide retained its substrate properties when flanked with two fluorescent proteins, providing a novel fluorescent resonance energy transfer approach for MS studies. Thus, anti-MBP autoantibody-mediated, epitope-specific binding and cleavage may be regarded as a specific characteristic of MS compared with OND and healthy donors and may serve as an additional biomarker of disease progression.
Authors:
Alexey A Belogurov; Inna N Kurkova; Alain Friboulet; Daniel Thomas; Viktor K Misikov; Maria Yu Zakharova; Sergey V Suchkov; Sergey V Kotov; Alexander I Alehin; Bérangère Avalle; Ekaterina A Souslova; Herbert C Morse; Alexander G Gabibov; Natalia A Ponomarenko
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Intramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  180     ISSN:  0022-1767     ISO Abbreviation:  J. Immunol.     Publication Date:  2008 Jan 
Date Detail:
Created Date:  2008-01-07     Completed Date:  2008-03-10     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1258-67     Citation Subset:  AIM; IM    
Affiliation:
Institute of Bioorganic Chemistry, Clinical Hospital, Russian Academy of Sciences, Moscow, Russia.
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
Aged
Amino Acid Sequence
Antibodies, Catalytic / immunology*
Autoantibodies / immunology*
Autoantigens / blood,  immunology
Biological Markers / blood,  metabolism
Enzyme-Linked Immunosorbent Assay
Epitope Mapping
Epitopes / blood*,  immunology*
Female
Fluorescence Resonance Energy Transfer
Humans
Male
Middle Aged
Molecular Sequence Data
Multiple Sclerosis / diagnosis*,  immunology
Myelin Basic Proteins / blood*,  immunology*
Peptide Library
Peptides / blood,  immunology
Substrate Specificity
Chemical
Reg. No./Substance:
0/Antibodies, Catalytic; 0/Autoantibodies; 0/Autoantigens; 0/Biological Markers; 0/Epitopes; 0/Myelin Basic Proteins; 0/Peptide Library; 0/Peptides

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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