Antibody Mediated Demyelination

  • A. Van Der Goes
  • E. C. W. Breij
  • M. Kortekaas
  • K. Hoekstra
  • P. J. H. Jongen
  • C. D. Dijkstra
  • S. Amor
Part of the Topics in Neuroscience book series (TOPNEURO)


Intrathecal oligoclonal IgG antibodies (Abs) are present in more than 90% of multiple sclerosis (MS) patients and the presence of such Abs serves as a laboratory marker supporting the diagnosis of this disease. The intrathecal IgG fractions contain Abs with many different specificities, including myelin-specific Abs. Reports on anti-myelin Abs in cerebrospinal (CSF) and sera are controversial [1-7]. Several reports describe the presence of anti-myelin Ab in serum and CSF, whereas others find anti-myelin Abs only in the CSF, and yet others report that anti-myelin Abs are absent in MS patients. However, B lymphocytes specific for, and plasma cells secreting Abs to myelin basic protein (MBP), myelin-associated glycoprotein (MAG), myelin oligodendrocyte glycoprotein (MOG), and proteolipid protein (PLP) are consistently detected in the central nervous system (CNS) of MS patients [8-11]. Such cells are even found in the CSF in the absence of anti-myelin Abs, suggesting that antibodies rapidly bind to target structures, such as the corresponding auto-antigens or to Fcreceptors, and therefore become undetectable [8, 9]. In organotypic, myelinated cultures of CNS tissue, sera of MS patients promoted myelin breakdown [12]. Similar results were obtained using rabbit anti-galactocerebroside (GalC) sera and anti-whole myelin sera [13, 14]. Genain et al. [15] identified auto-antibodies against MOG within acute MS lesions, where they were associated with damaged myelin membranes, and within macrophages ingesting myelin [15]. Lassmann et al. [16] described abundant deposition of immunoglobulins in a subclass of active MS.


Multiple Sclerosis Myelin Basic Protein Experimental Allergic Encephalomyelitis Myelin Oligodendrocyte Glyco Central Nervous System Tissue 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Möller JR et al (1989) Antibodies to myelin-associated glycoprotein (MAG) in the cerebrospinal fluid of multiple sclerosis patients. J Neuroimmunol 22:55–61PubMedCrossRefGoogle Scholar
  2. 2.
    Cruz M et al (1987) Immunoblot detection of oligoclonal anti-myelin basic protein IgG antibodies in cerebrospinal fluid in multiple sclerosis. Neurology 37:1515–1519PubMedCrossRefGoogle Scholar
  3. 3.
    Henneberg A et al (1991) Antibodies to brain tissue in sera of patients with chronic progressive multiple sclerosis. J Neuroimmunol 34:223–227PubMedCrossRefGoogle Scholar
  4. 4.
    Bernard CCA et al (1981) Antibody to myelin basic protein in extracts of multiple sclerosis brain. Immunology 43:447–457PubMedGoogle Scholar
  5. 5.
    Ryberg B, Jacque C (1986) Are anti-brain antibodies in multiple sclerosis directed to myelin basic protein. Acta Neurol Scand 73:247–252PubMedCrossRefGoogle Scholar
  6. 6.
    Wajgt A, Górny M (1983) CSF antibodies to myelin basic protein and to myelin-associated glycoprotein in multiple sclerosis. Evidence of the intrathecal production of antibodies. Acta Neurol Scand 68:337–343PubMedCrossRefGoogle Scholar
  7. 7.
    Xiao BX et al (1991) Antibodies to myelin-oligodendrocyte glycoprotein in cerebrospinal fluid from patients with multiple sclerosis and controls. J Neuroimmunol 31:91–96PubMedCrossRefGoogle Scholar
  8. 8.
    Sun JB et al (1991) T and B cell responses to myelin-oligodendrocye glycoprotein in multiple sclerosis. J Immunol 146:1490–1495PubMedGoogle Scholar
  9. 9.
    Sun JB et al (1991) Autoreactive T and B cells responding to myelin proteolipid in multiple sclerosis and controls. Eur J Immunol 21:1461–1468PubMedCrossRefGoogle Scholar
  10. 10.
    Baig S et al (1991) Multiple sclerosis: cells secreting antibodies against myelin-associated glycoprotein are present in cerebrospinal fluid. Scand J Immunol 33:73–79PubMedCrossRefGoogle Scholar
  11. 11.
    Link H et al (1990) Persistent anti-myelin basic protein IgG antibody response in multiple sclerosis cerebrospinal fluid. J Neuroimmunol 28:237–248PubMedCrossRefGoogle Scholar
  12. 12.
    Raine CS et al (1973) Multiple sclerosis: serum-induced demyelination in vitro. J Neurol Sci 20:127–148PubMedCrossRefGoogle Scholar
  13. 13.
    Seil FJ (1968) The in vitro demyelinating activity of sera from guinea pigs sensitized with while CNS and with purified encephalitogen. Exp Neurol 22:545–555PubMedCrossRefGoogle Scholar
  14. 14.
    Raine CS et al (1981) Demyelination in vitro: absorption studies demonstrate that galactocerebroside is a major target. J Neurolog Sci 52:117–131CrossRefGoogle Scholar
  15. 15.
    Genain CP et al (1999) Identification of autoantibodies with myelin damage in multiple sclerosis. Nat Med 5:170–175PubMedCrossRefGoogle Scholar
  16. 16.
    Lassmann H et al (2001) Heterogeneity of multiple sclerosis pathogenesis: implications for diagnosis and therapy. Trends Mol Med 7:115–121PubMedCrossRefGoogle Scholar
  17. 17.
    Morris MM et al (1998) Antibodies to myelin components modulate experimental allergic encephalomyelitis in Biozzi ABH (H-2Ag7) mice. Biochem Soc Trans 25:168S–173SGoogle Scholar
  18. 18.
    Linington C, Lassmann H (1987) Antibody responses in chronic relapsing experimental allergic encephalomyelitis: correlation of serum demyelinating activity with antibody titre to the myelin/oligodendrocyte glycoprotein (MOG). J Neuroimmunol 17:61–69PubMedCrossRefGoogle Scholar
  19. 19.
    Lassmann H et al (1981) In vivo effect of sera from animals with chronic relapsing experimental allergic encephalomyelitis on central and peripheral myelin. Acta Neuropathol (Berl) 55:297–306CrossRefGoogle Scholar
  20. 20.
    Moore GRW et al (1984) Experimental autoimmune encephalomyelitis: augmentation of demyelination by different myelin lipids. Lab Invest 51:416–424PubMedGoogle Scholar
  21. 21.
    Linington C et al (1988) Augmentation of demyelination in rat acute allergic encephalomyelitis by circulating mouse monoclonal antibodies directed against a myelin/ologodendrocyte glycoprotein. Am J Pathol 130:443–454PubMedGoogle Scholar
  22. 22.
    Schluesner HJ et al (1987) A monoclonal antibody against a myelin ologodendrocyte glycoprotein induces relapses and demyelination in central nervous system autoimmune disease. J Immunol 139:4016–4021Google Scholar
  23. 23.
    Piddlesden SJ et al (1993) The demyelinating potential of antibodies to myelin oligodendrocyte glycoprotein is related to their ability to fix complement. Am J Pathol 143:555–564PubMedGoogle Scholar
  24. 24.
    Piddlesden SJ et al (1991) Antibody-mediated demyelination in experimental allergic encephalomyelitis is independent of complement membrane attack complex formation. Exp Immunol 83:245–250CrossRefGoogle Scholar
  25. 25.
    Piddlesden SJ et al (1994) Soluble recombinant complement receptor 1 inhibits inflammation and demyelination in antibody-mediated demyelinating experimental allergic encephalomyelitis. J Immunol 152:5477–5484PubMedGoogle Scholar
  26. 26.
    Van der Goes A et al (1999) The role of anti-myelin (auto)-antibodies in the phagocytosis of myelin by macrophages. J Neuroimmunol 101:61–67PubMedCrossRefGoogle Scholar
  27. 27.
    Abdul-Majid K et al (2002) Fc Receptors are critical for autoimmune inflammatory damage to the central nervous system in experimental autoimmune encephalomyelitis. Scand J Immunol 55:70–81PubMedCrossRefGoogle Scholar
  28. 28.
    Lock C (2002) Gene-microarray analysis of multiple sclerosis lesions yields new targets validated in autoimmune encephalomyelitis. Nat Med 8:500–508PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Italia 2004

Authors and Affiliations

  • A. Van Der Goes
  • E. C. W. Breij
  • M. Kortekaas
  • K. Hoekstra
  • P. J. H. Jongen
  • C. D. Dijkstra
  • S. Amor

There are no affiliations available

Personalised recommendations