Axonal and oligodendrocyte-localized IgM and IgG deposits in MS lesions

J Neuroimmunol. 2012 Jun 15;247(1-2):86-94. doi: 10.1016/j.jneuroim.2012.03.020. Epub 2012 Apr 23.


Background: Recent findings support the important role of antibodies in multiple sclerosis (MS) physiopathology. Thus, local IgG synthesis is a hallmark of the disease, and intrathecal IgM synthesis associates with a poor disease outcome.

Methodology: The aim of this study was to investigate the presence of IgM and IgG in demyelinating lesions using high sensitivity immunohistochemistry techniques in necropsies from fourteen MS patients, four controls without neurological disease and four cases with non MS CNS inflammatory disease.

Results: IgG and IgM were absent in controls. Conversely, we found IgM in about 50% and IgG in 75% of MS patients. The presence of IgM and IgG antibodies was independent of disease duration, clinical disease type or lesion stage. IgM and IgG were present in acute, chronic active and chronic inactive lesions. Double immunofluorescence showed that IgM and IgG were detected on axons and oligodendrocytes in demyelinated areas. Moreover, we observed immunoglobulin deposits on oligodendrocytes in NAWM in some cases. IgG and IgM colocalized with complement C3b on demyelinated axons and oligodendrocytes and antibody-antigen immunocomplexes were detected in foamy macrophages in active lesion areas. These findings were absent from cases of non-neurological disease and cases with non-MS CNS inflammatory disease.

Significance of the study: These observations provide further evidence on the role of antibodies, complement and macrophages in plaque development, and strongly suggest they can induce axonal injury, an important cause of disability in MS. They may provide novel therapeutic strategies to limit tissue degeneration in the disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Axons / pathology*
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Cerebellum / pathology
  • Complement C3b / metabolism
  • DNA-Binding Proteins / metabolism
  • Female
  • Humans
  • Immunoglobulin G / immunology
  • Immunoglobulin G / metabolism*
  • Immunoglobulin M / immunology
  • Immunoglobulin M / metabolism*
  • Macrophages / metabolism
  • Macrophages / pathology
  • Male
  • Middle Aged
  • Multiple Sclerosis / immunology
  • Multiple Sclerosis / pathology*
  • Nerve Tissue Proteins / metabolism
  • Oligodendrocyte Transcription Factor 2
  • Oligodendroglia / immunology
  • Oligodendroglia / metabolism*
  • Phosphopyruvate Hydratase / metabolism
  • Transcription Factors / metabolism


  • Basic Helix-Loop-Helix Transcription Factors
  • DNA-Binding Proteins
  • Immunoglobulin G
  • Immunoglobulin M
  • MYT1 protein, human
  • Nerve Tissue Proteins
  • OLIG2 protein, human
  • Oligodendrocyte Transcription Factor 2
  • Transcription Factors
  • Complement C3b
  • Phosphopyruvate Hydratase