Recognition and degradation of myelin basic protein peptides by serum autoantibodies: novel biomarker for multiple sclerosis.
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.
Belogurov
Alexey A
AA
Institute of Bioorganic Chemistry, Clinical Hospital, Russian Academy of Sciences, Moscow, Russia.
Kurkova
Inna N
IN
Friboulet
Alain
A
Thomas
Daniel
D
Misikov
Viktor K
VK
Zakharova
Maria Yu
MY
Suchkov
Sergey V
SV
Kotov
Sergey V
SV
Alehin
Alexander I
AI
Avalle
Bérangère
B
Souslova
Ekaterina A
EA
Morse
Herbert C
HC
Gabibov
Alexander G
AG
Ponomarenko
Natalia A
NA
D000293:Adolescent; D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D017151:Antibodies, Catalytic / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology*; D001324:Autoantigens / Q000097:blood / Q000276:immunology; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D018604:Epitope Mapping; D000939:Epitopes / Q000097:blood* / Q000276:immunology*; D005260:Female; D031541:Fluorescence Resonance Energy Transfer; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009103:Multiple Sclerosis / Q000175:diagnosis* / Q000276:immunology; D004676:Myelin Basic Protein / Q000097:blood* / Q000276:immunology*; D019151:Peptide Library; D010455:Peptides / Q000097:blood / Q000276:immunology; D013379:Substrate Specificity
D017151:Antibodies, Catalytic; D001323:Autoantibodies; D001324:Autoantigens; D015415:Biomarkers; D000939:Epitopes; D004676:Myelin Basic Protein; D019151:Peptide Library; D010455:Peptides