Abstract
Elevated titers of serum antibodies against GM1-ganglioside are associated with a variety of autoimmune neuropathies. Although much evidence indicates that these autoantibodies play a primary role in the disease processes, the mechanism of their appearance is unclear. Low-affinity anti-GM1 antibodies of the IgM isotype are part of the normal human immunological repertoire. In patients with motor syndromes, we found that in addition to the usual anti-GM1 antibodies, the sera contain IgM-antibodies that recognize GM1 with higher affinity and/or different specificity. This latter type of antibodies was not detected in other autoimmune diseases. We studied the fine specificity of both normal and motor disease-associated antibodies using HPTLC-immunostaining of GM1 and structurally related glycolipids, soluble antigen binding inhibition, and GM1 affinity columns. Normal low-affinity anti-GM1 antibodies cross-react with GA1 and/or GD1b. In the motor syndrome patients, different populations of antibodies characterized by their affinity and cross-reactivity were detected. Although one population is relatively common (low affinity, not cross-reacting with GA1 and GD1b), there are remarkably few sera having the same set of populations. These results suggest that the appearance of the new antibody populations is a random process. When the different antibody populations were analyzed in relation to the three-dimensional structure of GM1, a restricted area of the GM1 oligosaccharide (the terminal Galβ1-3GalNAc) was found to be involved in binding of normal anti-GM1 antibodies. Patient antibodies recognize slightly different areas, including additional regions of the GM1 molecule such as the NeuNAc residue. We hypothesize that disease-associated antibodies may originate by spontaneous mutation of normal occurring antibodies.
Original language | English (US) |
---|---|
Pages (from-to) | 131-136 |
Number of pages | 6 |
Journal | Journal of Neuroimmunology |
Volume | 119 |
Issue number | 1 |
DOIs | |
State | Published - Sep 3 2001 |
Externally published | Yes |
Keywords
- Anti-GM antibodies
- Autoantibodies
- Autoimmune neuropathy
- GM
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
- Neurology
- Clinical Neurology