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Variable patterns of anti-GM(1) IgM-antibody populations defined by affinity and fine specificity in patients with motor syndromes: evidence for their random origin.

Abstract：

:Elevated titers of serum antibodies against GM(1)-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-GM(1) 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-GM(1) antibodies, the sera contain IgM-antibodies that recognize GM(1) 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 GM(1) and structurally related glycolipids, soluble antigen binding inhibition, and GM(1) affinity columns. Normal low-affinity anti-GM(1) antibodies cross-react with GA(1) and/or GD(1b). 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 GA(1) and GD(1b)), 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 GM(1), a restricted area of the GM(1) oligosaccharide (the terminal Galbeta1-3GalNAc) was found to be involved in binding of normal anti-GM(1) antibodies. Patient antibodies recognize slightly different areas, including additional regions of the GM(1) molecule such as the NeuNAc residue. We hypothesize that disease-associated antibodies may originate by spontaneous mutation of normal occurring antibodies.

journal_name

J Neuroimmunol

journal_title

Journal of neuroimmunology

authors

Lopez PH,Lardone RD,Irazoqui FJ,Villa AM,Di Egidio M,Saizar RD,Sica RE,Nores GA

doi

10.1016/s0165-5728(01)00355-1

subject

Has Abstract

pub_date

2001-09-03 00:00:00

pages

131-6

issue

eissn

0165-5728

issn

1872-8421

pii

S0165-5728(01)00355-1

journal_volume

119

pub_type

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Variable patterns of anti-GM(1) IgM-antibody populations defined by affinity and fine specificity in patients with motor syndromes: evidence for their random origin.