Recognition and degradation of myelin basic protein peptides by serum autoantibodies: Novel biomarker for multiple sclerosis

被引:94
作者
Belogurov, Alexey A., Jr. [1 ]
Kurkova, Inna N. [1 ]
Friboulet, Alain [4 ]
Thomas, Daniel [4 ]
Misikov, Viktor K. [3 ]
Zakharova, Maria Yu. [1 ]
Suchkov, Sergey V. [3 ]
Kotov, Sergey V. [3 ]
Alehin, Alexander I. [2 ]
Avalle, Berangere [4 ]
Souslova, Ekaterina A. [1 ]
Morse, Herbert C., III [5 ]
Gabibov, Alexander G. [1 ,6 ]
Pononlarenko, Natalia A. [1 ]
机构
[1] Russian Acad Sci, Inst Bioorgan Chem, Moscow, Russia
[2] Russian Acad Sci, Clin Hosp, Moscow, Russia
[3] Vladimirsky Moscow REg Clin Inst, Moscow, Russia
[4] Univ Technol Compiegne, CNRS, Unite Mixte Rech, F-60206 Compiegne, France
[5] NIAID, Immunopathol Lab, Natl Inst Hlth, Rockville, MD 20852 USA
[6] Russian Acad Sci, Inst Gene Biol, Moscow, Russia
关键词
D O I
10.4049/jimmunol.180.2.1258
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:1258 / 1267
页数:10
相关论文
共 48 条
[1]   Antimyelin antibodies as a predictor of clinically definite multiple sclerosis after a first demyelinating event [J].
Berger, T ;
Rubner, P ;
Schautzer, F ;
Egg, R ;
Ulmer, H ;
Mayringer, I ;
Dilitz, E ;
Deisenhammer, F ;
Reindl, M .
NEW ENGLAND JOURNAL OF MEDICINE, 2003, 349 (02) :139-145
[2]   Interferon-γ regulates cathepsin G activity in microglia-derived lysosomes and controls the proteolytic processing of myelin basic protein in vitro [J].
Burster, Timo ;
Beck, Alexander ;
Poeschel, Simone ;
Oren, Anita ;
Baechle, Daniel ;
Reich, Michael ;
Roetzschke, Olaf ;
Falk, Kirsten ;
Boehm, Bernhard O. ;
Youssef, Sawsan ;
Kalbacher, Hubert ;
Overkleeft, Herman ;
Tolosa, Eva ;
Driessen, Christoph .
IMMUNOLOGY, 2007, 121 (01) :82-93
[3]  
Cao LG, 1999, BIOCHEMISTRY-US, V38, P6157
[4]   MRI and the diagnosis of multiple sclerosis: expanding the concept of "no better explanation" [J].
Charil, Arnaud ;
Yousry, Tarek A. ;
Rovaris, Marco ;
Barkhof, Frederik ;
De Stefano, Nicola ;
Fazekas, Franz ;
Miller, David H. ;
Montalban, Xavier ;
Simon, Jack H. ;
Polman, Chris ;
Filippi, Massimo .
LANCET NEUROLOGY, 2006, 5 (10) :841-852
[5]   Autocatalytic cleavage of myelin basic protein: An alternative to molecular mimicry [J].
D'Souza, CA ;
Wood, DD ;
She, YM ;
Moscarello, MA .
BIOCHEMISTRY, 2005, 44 (38) :12905-12913
[6]   Differences in susceptibility of MBP charge isomers to digestion by stromelysin-1 (MMP-3) and release of an immunodominant epitope [J].
D'Souza, Cheryl A. ;
Moscarello, Mario A. .
NEUROCHEMICAL RESEARCH, 2006, 31 (08) :1045-1054
[7]   Post-translational protein modifications in antigen recognition and autoimmunity [J].
Doyle, HA ;
Mamula, MJ .
TRENDS IN IMMUNOLOGY, 2001, 22 (08) :443-449
[8]   DIRECT BINDING OF MYELIN BASIC-PROTEIN AND SYNTHETIC COPOLYMER-1 TO CLASS-II MAJOR HISTOCOMPATIBILITY COMPLEX-MOLECULES ON LIVING ANTIGEN-PRESENTING CELLS - SPECIFICITY AND PROMISCUITY [J].
FRIDKISHARELI, M ;
TEITELBAUM, D ;
GUREVICH, E ;
PECHT, I ;
BRAUTBAR, C ;
KWON, OJ ;
BRENNER, T ;
ARNON, R ;
SELA, M .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (11) :4872-4876
[9]   DNA-HYDROLYZING AUTOANTIBODIES [J].
GABIBOV, AG ;
GOLOLOBOV, GV ;
MAKAREVICH, OI ;
SCHOUROV, DV ;
CHERNOVA, EA ;
YADAV, RP .
APPLIED BIOCHEMISTRY AND BIOTECHNOLOGY, 1994, 47 (2-3) :293-303
[10]   Identification of autoantibodies associated with myelin damage in multiple sclerosis [J].
Genain, CP ;
Cannella, B ;
Hauser, SL ;
Raine, CS .
NATURE MEDICINE, 1999, 5 (02) :170-175