Variable patterns of anti-GM1 IgM-antibody populations defined by affinity and fine specificity in patients with motor syndromes: Evidence for their random origin

P. H.H. Lopez, R. D. Lardone, F. J. Irazoqui, A. M. Villa, M. Di Egidio, R. D. Saizar, R. E.P. Sica, G. A. Nores

Research output: Contribution to journalArticlepeer-review

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 languageEnglish (US)
Pages (from-to)131-136
Number of pages6
JournalJournal of Neuroimmunology
Volume119
Issue number1
DOIs
StatePublished - Sep 3 2001

Keywords

  • Anti-GM antibodies
  • Autoantibodies
  • Autoimmune neuropathy
  • GM

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Neurology
  • Clinical Neurology

Fingerprint Dive into the research topics of 'Variable patterns of anti-GM<sub>1</sub> IgM-antibody populations defined by affinity and fine specificity in patients with motor syndromes: Evidence for their random origin'. Together they form a unique fingerprint.

Cite this