| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
* Institute of Bioorganic Chemistry,
Institute of Gene Biology, and
Clinical Hospital, Russian Academy of Sciences and
Vladimirsky Moscow Region Clinical Institute, Moscow, Russia;
¶ Centre National de la Recherche Scientifique, Unité Mixte de Recherche, Compiègne Technological University, Compiègne, France; and
|| Laboratory of Immunopathology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852
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.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by Biotechnology Engagement Program Grant 37. The work was also supported in part by grants from the European Union International Cooperation-Copernicus program (IC15 CT96-0909), International Centre for Genetic Engineering and Biotechnology Grant CRP/RUS04-03, the Scientific Russian Schools Program 1800.2003.4, Program on Fundamental Medicine of the Russian Academy of Sciences and Russian Foundation of Basic Research (Grant 03-04-48836-a), Network and the Intramural Research Program of the National Institutes of Health and the National Institute of Allergy and Infectious Diseases. A.A.B. was also supported by the Russian Science Support Foundation.
2 Address correspondence and reprint requests to Dr. Alexander Gabibov, Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklucho-Maklaia 16/10, Moscow, Russia. E-mail address: gabibov{at}ibch.ru
3 Abbreviations used in this paper: MS, multiple sclerosis; CDMS, clinically definite MS; CIS, clinically isolated syndrome; EDSS, expanded disability status scale; EPeFRET, encephalitogenic peptide fluorescent resonance energy transfer; FRET, fluorescent resonance energy transfer; MBP, myelin basic protein; MMP-3, matrix metalloproteinase 3; MOG, myelin oligodendrocyte glycoprotein; MRI, magnetic resonance imaging; OND, other neurological diseases; RR, relapsing-remitting (MS); PP, primary progressive (MS); SP, secondary progressive (MS); SELDI, surface-enhanced laser desorption/ionization; Trx, thioredoxin.
This article has been cited by other articles:
|
|
 |
|
  V. Sharma, W. Heriot, K. Trisler, and V. Smider A Human Germ Line Antibody Light Chain with Hydrolytic Properties Associated with Multimerization Status J. Biol. Chem., November 27, 2009; 284(48): 33079 - 33087. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-H. Yang, C.-J. Chang, Y.-H. Chuang, H.-Y. Hsu, P. P. Chen, and B.-L. Chiang Identification of anti-prothrombin antibodies in the anti-phospholipid syndrome that display the prothrombinase activity Rheumatology, November 17, 2009; (2009) kep328v1. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
