Brain, Vol. 122, No. 11, 2047-2056,
November 1999
© 1999 Oxford University Press
Invited review |
Antibodies against the myelin oligodendrocyte glycoprotein and the myelin basic protein in multiple sclerosis and other neurological diseases: a comparative study
1 Department of Neurology, University of Innsbruck, Innsbruck, Austria and 2 Department of Neuroimmunology, Max Planck Institute for Neurobiology, Martinsried, Germany
Correspondence to:
Dr T. Berger, Department of Neurology, University of Innsbruck, Anichstrasse 35, A-6020 Innsbruck, Austria E-mail: Thomas.Berger{at}uibk.ac.at
In experimental animal models of multiple sclerosis demyelinating antibody responses are directed against the myelin oligodendrocyte glycoprotein (MOG). We have investigated whether a similar antibody response is also present in multiple sclerosis patients. Using the recombinant human extracellular immunoglobulin domain of MOG (MOG-Ig) we have screened the sera and CSFs of 130 multiple sclerosis patients, 32 patients with other inflammatory neurological diseases (OIND), 30 patients with other non-inflammatory neurological diseases (ONND) and 10 patients with rheumatoid arthritis. We report that 38% of multiple sclerosis patients are seropositive for IgG antibodies to MOG-Ig compared with 28% seropositive for anti-myelin basic protein (MBP). In contrast, OIND are characterized by similar frequencies of serum IgG antibody responses to MOG-Ig (53%) and MBP (47%), whereas serum IgG responses to MOG-Ig are rare in ONND (3%) and rheumatoid arthritis (10%). Anti-MBP IgG antibodies, however, are a frequent finding in ONND (23%) and rheumatoid arthritis (60%). Our results provide clear evidence that anti-MOG-Ig antibodies are common in CNS inflammation. However, in OIND these antibody responses are transient, whereas they persist in multiple sclerosis. We demonstrate that the serum anti-MOG-Ig response is already established in early multiple sclerosis (multiple sclerosis-R0; 36%). In later multiple sclerosis stages frequencies and titres are comparable with early multiple sclerosis. In contrast, the frequency of anti-MBP antibodies is low in multiple sclerosis-R0 (12%) and increases during disease progression in relapsing–remitting (32%) and chronic progressive multiple sclerosis (40%), thus suggesting that anti-MBP responses accumulate over time. Finally we provide evidence for intrathecal synthesis of IgG antibodies to MOG-Ig in multiple sclerosis.
multiple sclerosis; autoantibodies; myelin oligodendrocyte glycoprotein; myelin basic protein; brain inflammation
ELISA = enzyme-linked immunosorbent assay; Ig = immunoglobulin; MBP = myelin basic protein; MOG = myelin oligodendrocyte glycoprotein; MOG-Ig = extracellular immunoglobulin domain of MOG; multiple sclerosis-CP = multiple sclerosis, chronic progressive disease course; multiple sclerosis-R0 = multiple sclerosis, first attack; multiple sclerosis-RR = multiple sclerosis, relapsing–remitting disease course; OIND = other inflammatory neurological diseases; ONND = other non-inflammatory neurological diseases; Q-Alb = albumin quotient
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M H J Vogt, C E Teunissen, E Iacobaeus, D A M Heijnen, E C W Breij, T Olsson, L Brundin, J Killestein, and C. D Dijkstra Cerebrospinal fluid anti-myelin antibodies are related to magnetic resonance measures of disease activity in multiple sclerosis J. Neurol. Neurosurg. Psychiatry, October 1, 2009; 80(10): 1110 - 1115. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. A. McLaughlin, T. Chitnis, J. Newcombe, B. Franz, J. Kennedy, S. McArdel, J. Kuhle, L. Kappos, K. Rostasy, D. Pohl, et al. Age-Dependent B Cell Autoimmunity to a Myelin Surface Antigen in Pediatric Multiple Sclerosis J. Immunol., September 15, 2009; 183(6): 4067 - 4076. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Breithaupt, B. Schafer, H. Pellkofer, R. Huber, C. Linington, and U. Jacob Demyelinating Myelin Oligodendrocyte Glycoprotein-Specific Autoantibody Response Is Focused on One Dominant Conformational Epitope Region in Rodents J. Immunol., July 15, 2008; 181(2): 1255 - 1263. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Somers, C. Govarts, K. Somers, R. Hupperts, R. Medaer, and P. Stinissen Autoantibody Profiling in Multiple Sclerosis Reveals Novel Antigenic Candidates J. Immunol., March 15, 2008; 180(6): 3957 - 3963. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Tomassini, L. De Giglio, M. Reindl, P. Russo, I. Pestalozza, P. Pantano, T. Berger, and C. Pozzilli Anti-myelin antibodies predict the clinical outcome after a first episode suggestive of MS Multiple Sclerosis, November 1, 2007; 13(9): 1086 - 1094. [Abstract] [PDF]
|
|
|
|
|
|
J.-F. Jegou, P. Chan, M.-T. Schouft, M. R. Griffiths, J. W. Neal, P. Gasque, H. Vaudry, and M. Fontaine C3d Binding to the Myelin Oligodendrocyte Glycoprotein Results in an Exacerbated Experimental Autoimmune Encephalomyelitis J. Immunol., March 1, 2007; 178(5): 3323 - 3331. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Kuhle, C. Pohl, M. Mehling, G. Edan, M. S. Freedman, H.-P. Hartung, C. H. Polman, D. H. Miller, X. Montalban, F. Barkhof, et al. Lack of Association between Antimyelin Antibodies and Progression to Multiple Sclerosis N. Engl. J. Med., January 25, 2007; 356(4): 371 - 378. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Pelayo, M. Tintore, X. Montalban, A. Rovira, C. Espejo, M. Reindl, and T. Berger Antimyelin Antibodies with No Progression to Multiple Sclerosis N. Engl. J. Med., January 25, 2007; 356(4): 426 - 428. [Full Text] [PDF]
|
|
|
|
|
|
S J Pittock, M Reindl, S Achenbach, T Berger, W Bruck, F Konig, Y Morales, H Lassmann, S Bryant, S B Moore, et al. Myelin oligodendrocyte glycoprotein antibodies in pathologically proven multiple sclerosis: frequency, stability and clinicopathologic correlations Multiple Sclerosis, January 1, 2007; 13(1): 7 - 16. [Abstract] [PDF]
|
|
|
|
 |
|
 D. Zhou, R. Srivastava, S. Nessler, V. Grummel, N. Sommer, W. Bruck, H.-P. Hartung, C. Stadelmann, and B. Hemmer Identification of a pathogenic antibody response to native myelin oligodendrocyte glycoprotein in multiple sclerosis PNAS, December 12, 2006; 103(50): 19057 - 19062. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S Rauer, B Euler, M Reindl, and T Berger Antimyelin antibodies and the risk of relapse in patients with a primary demyelinating event. J. Neurol. Neurosurg. Psychiatry, June 1, 2006; 77(6): 739 - 742. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. A. Ponomarenko, O. M. Durova, I. I. Vorobiev, A. A. Belogurov Jr., I. N. Kurkova, A. G. Petrenko, G. B. Telegin, S. V. Suchkov, S. L. Kiselev, M. A. Lagarkova, et al. Autoantibodies to myelin basic protein catalyze site-specific degradation of their antigen PNAS, January 10, 2006; 103(2): 281 - 286. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E T Lim, T Berger, M Reindl, C M Dalton, K Fernando, G Keir, E J Thompson, D H Miller, and G Giovannoni Anti-myelin antibodies do not allow earlier diagnosis of multiple sclerosis Multiple Sclerosis, August 1, 2005; 11(4): 492 - 494. [Abstract] [PDF]
|
|
|
|
|
|
K. C. O'Connor, H. Appel, L. Bregoli, M. E. Call, I. Catz, J. A. Chan, N. H. Moore, K. G. Warren, S. J. Wong, D. A. Hafler, et al. Antibodies from Inflamed Central Nervous System Tissue Recognize Myelin Oligodendrocyte Glycoprotein J. Immunol., August 1, 2005; 175(3): 1974 - 1982. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Lolli, B. Mulinacci, A. Carotenuto, B. Bonetti, G. Sabatino, B. Mazzanti, A. M. D'Ursi, E. Novellino, M. Pazzagli, L. Lovato, et al. An N-glucosylated peptide detecting disease-specific autoantibodies, biomarkers of multiple sclerosis PNAS, July 19, 2005; 102(29): 10273 - 10278. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. B. Marta, M. B. Montano, C. M. Taylor, A. L. Taylor, R. Bansal, and S. E. Pfeiffer Signaling Cascades Activated upon Antibody Cross-linking of Myelin Oligodendrocyte Glycoprotein: POTENTIAL IMPLICATIONS FOR MULTIPLE SCLEROSIS J. Biol. Chem., March 11, 2005; 280(10): 8985 - 8993. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Ebringer, L. Hughes, T. Rashid, and C. Wilson Acinetobacter Immune Responses in Multiple Sclerosis: Etiopathogenetic Role and Its Possible Use as a Diagnostic Marker Arch Neurol, January 1, 2005; 62(1): 33 - 36. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Sakuma, K. Kohyama, I.-K. Park, A. Miyakoshi, N. Tanuma, and Y. Matsumoto Clinicopathological study of a myelin oligodendrocyte glycoprotein-induced demyelinating disease in LEW.1AV1 rats Brain, October 1, 2004; 127(10): 2201 - 2213. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. T. Reder and J. J. Oger Anti-myelin oligodendrocyte glycoprotein antibodies in multiple sclerosis Neurology, June 8, 2004; 62(11): 1922 - 1923. [Full Text] [PDF]
|
|
|
|
|
|
V. Lampasona, D. Franciotta, R. Furlan, S. Zanaboni, R. Fazio, E. Bonifacio, G. Comi, and G. Martino Similar low frequency of anti-MOG IgG and IgM in MS patients and healthy subjects Neurology, June 8, 2004; 62(11): 2092 - 2094. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Mantegazza, P. Cristaldini, P. Bernasconi, F. Baggi, R. Pedotti, I. Piccini, N. Mascoli, L. L. Mantia, C. Antozzi, O. Simoncini, et al. Anti-MOG autoantibodies in Italian multiple sclerosis patients: specificity, sensitivity and clinical association Int. Immunol., April 1, 2004; 16(4): 559 - 565. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Lily, J. Palace, and A. Vincent Serum autoantibodies to cell surface determinants in multiple sclerosis: a flow cytometric study Brain, February 1, 2004; 127(2): 269 - 279. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Guggenmos, A. S. Schubart, S. Ogg, M. Andersson, T. Olsson, I. H. Mather, and C. Linington Antibody Cross-Reactivity between Myelin Oligodendrocyte Glycoprotein and the Milk Protein Butyrophilin in Multiple Sclerosis J. Immunol., January 1, 2004; 172(1): 661 - 668. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. A. Maguire, R. Mantegazza, A. Chaudhuri, P. O. Behan, T. Berger, and M. Reindl Antimyelin Antibodies in Multiple Sclerosis N. Engl. J. Med., December 4, 2003; 349(23): 2269 - 2271. [Full Text] [PDF]
|
|
|
|
|
|
T. Berger, P. Rubner, F. Schautzer, R. Egg, H. Ulmer, I. Mayringer, E. Dilitz, F. Deisenhammer, and M. Reindl Antimyelin Antibodies as a Predictor of Clinically Definite Multiple Sclerosis after a First Demyelinating Event N. Engl. J. Med., July 10, 2003; 349(2): 139 - 145. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. B. Marta, C. M. Taylor, T. Coetzee, T. Kim, S. Winkler, R. Bansal, and S. E. Pfeiffer Antibody Cross-Linking of Myelin Oligodendrocyte Glycoprotein Leads to Its Rapid Repartitioning into Detergent-Insoluble Fractions, and Altered Protein Phosphorylation and Cell Morphology J. Neurosci., July 2, 2003; 23(13): 5461 - 5471. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Khare, M. Rodriguez, and C. S. David HLA class II transgenic mice authenticate restriction of myelin oligodendrocyte glycoprotein-specific immune response implicated in multiple sclerosis pathogenesis Int. Immunol., April 1, 2003; 15(4): 535 - 546. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Weissert, J. Kuhle, K. L. de Graaf, W. Wienhold, M. M. Herrmann, C. Muller, T. G. Forsthuber, K.-H. Wiesmuller, and A. Melms High Immunogenicity of Intracellular Myelin Oligodendrocyte Glycoprotein Epitopes J. Immunol., July 1, 2002; 169(1): 548 - 556. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.-C. von Budingen, S. L. Hauser, A. Fuhrmann, C. B. Nabavi, J. I. Lee, and C. P. Genain Molecular characterization of antibody specificities against myelin/oligodendrocyte glycoprotein in autoimmune demyelination PNAS, June 11, 2002; 99(12): 8207 - 8212. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. K. U. Koehler, C. P. Genain, B. Giesser, and S. L. Hauser The Human T Cell Response to Myelin Oligodendrocyte Glycoprotein: A Multiple Sclerosis Family-Based Study J. Immunol., June 1, 2002; 168(11): 5920 - 5927. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. E. Hughes, S. Bonell, R. S. Natt, C. Wilson, H. Tiwana, A. Ebringer, P. Cunningham, V. Chamoun, E. J. Thompson, J. Croker, et al. Antibody Responses to Acinetobacter spp. and Pseudomonas aeruginosa in Multiple Sclerosis: Prospects for Diagnosis Using the Myelin-Acinetobacter-Neurofilament Antibody Index Clin. Vaccine Immunol., November 1, 2001; 8(6): 1181 - 1188. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. D. Smith, P. M. Kelley, J. W. Askew, D. M. Hoover, K. E. Deffenbacher, J. Gayan, A. M. Brower, and R. K. Olson Reading Disability and Chromosome 6p21.3: Evaluation of MOG as a Candidate Gene J Learn Disabil, November 1, 2001; 34(6): 512 - 519. [Abstract] [PDF]
|
|
|
|
|
|
R Egg, M Reindl, F Deisenhammer, C Linington, and T Berger Anti-MOG and anti-MBP antibody subclasses in multiple sclerosis Multiple Sclerosis, October 1, 2001; 7(5): 285 - 289. [Abstract] [PDF]
|
|
|
|
|
|
R. Weissert, K. L. de Graaf, M. K. Storch, S. Barth, C. Linington, H. Lassmann, and T. Olsson MHC Class II-Regulated Central Nervous System Autoaggression and T Cell Responses in Peripheral Lymphoid Tissues Are Dissociated in Myelin Oligodendrocyte Glycoprotein-Induced Experimental Autoimmune Encephalomyelitis J. Immunol., June 15, 2001; 166(12): 7588 - 7599. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Bruck, K. Neubert, T. Berger, and J. R Weber Clinical, radiological, immunological and pathological findings in inflammatory CNS demyelination-possible markers for an antibody-mediated process Multiple Sclerosis, June 1, 2001; 7(3): 173 - 177. [Abstract] [PDF]
|
|
|
|
|
|
H. Lassmann The New Pathology of Multiple Sclerosis Multiple Sclerosis, December 1, 2000; 6(6): 409 - 410. [PDF]
|
|
|
|
|
|
A. Stefferl, A. Schubart, M. Storch2, A. Amini, I. Mather, H. Lassmann, and C. Linington Butyrophilin, a Milk Protein, Modulates the Encephalitogenic T Cell Response to Myelin Oligodendrocyte Glycoprotein in Experimental Autoimmune Encephalomyelitis J. Immunol., September 1, 2000; 165(5): 2859 - 2865. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. J. Barkovich Concepts of Myelin and Myelination in Neuroradiology AJNR Am. J. Neuroradiol., June 1, 2000; 21(6): 1099 - 1109. [Full Text]
|
|
|
|
|
|
R.-B. Lindert, C. G. Haase, U. Brehm, C. Linington, H. Wekerle, and R. Hohlfeld Multiple sclerosis: B- and T-cell responses to the extracellular domain of the myelin oligodendrocyte glycoprotein Brain, November 1, 1999; 122(11): 2089 - 2100. [Abstract] [Full Text] [PDF]
|
|