Abstract
Elevated titers of serum antibodies against GM1-ganglioside are associated with a variety of autoimmune neuropathies. The origin of these autoantibodies is still unknown, although there is evidence that they are produced by CD5+ B-lymphocytes and that antigen mimicry is involved. Anti-GM1 IgM-antibodies in the normal human immunological repertoire are low affinity antibodies that cross-react with other glycoconjugates carrying Galβ1-3GalNAc and probably do not have GM1-mediated biological activity. Other anti-GM1 IgM-antibodies with higher affinity and/or different fine specificity are present in patients with motor syndromes. Based on our studies of structural requirement for binding, we hypothesize that disease-associated anti-GM1 antibodies originate at random by mutations affecting the binding site of naturally-occurring ones. The hypothesis is conceptually similar to the established phenomenon of "genetic drift" in species evolutionary biology and is therefore termed "binding site drift".
| Original language | English (US) |
|---|---|
| Pages (from-to) | 687-695 |
| Number of pages | 9 |
| Journal | Neurochemical Research |
| Volume | 27 |
| Issue number | 7-8 |
| DOIs | |
| State | Published - Aug 2002 |
| Externally published | Yes |
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Keywords
- Anti-GM antibodies
- Antigen mimicry
- Autoimmune neuropathy
- Binding site drift
- Binding site expansion
- Gangliosides
ASJC Scopus subject areas
- Neuroscience(all)
- Biochemistry
Cite this
The origin of anti-GM1 antibodies in neuropathies : The "binding site drift" hypothesis. / Lopez, Pablo; Lardone, R. D.; Irazoqui, F. J.; Maccioni, M.; Nores, G. A.
In: Neurochemical Research, Vol. 27, No. 7-8, 08.2002, p. 687-695.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The origin of anti-GM1 antibodies in neuropathies
T2 - The "binding site drift" hypothesis
AU - Lopez, Pablo
AU - Lardone, R. D.
AU - Irazoqui, F. J.
AU - Maccioni, M.
AU - Nores, G. A.
PY - 2002/8
Y1 - 2002/8
N2 - Elevated titers of serum antibodies against GM1-ganglioside are associated with a variety of autoimmune neuropathies. The origin of these autoantibodies is still unknown, although there is evidence that they are produced by CD5+ B-lymphocytes and that antigen mimicry is involved. Anti-GM1 IgM-antibodies in the normal human immunological repertoire are low affinity antibodies that cross-react with other glycoconjugates carrying Galβ1-3GalNAc and probably do not have GM1-mediated biological activity. Other anti-GM1 IgM-antibodies with higher affinity and/or different fine specificity are present in patients with motor syndromes. Based on our studies of structural requirement for binding, we hypothesize that disease-associated anti-GM1 antibodies originate at random by mutations affecting the binding site of naturally-occurring ones. The hypothesis is conceptually similar to the established phenomenon of "genetic drift" in species evolutionary biology and is therefore termed "binding site drift".
AB - Elevated titers of serum antibodies against GM1-ganglioside are associated with a variety of autoimmune neuropathies. The origin of these autoantibodies is still unknown, although there is evidence that they are produced by CD5+ B-lymphocytes and that antigen mimicry is involved. Anti-GM1 IgM-antibodies in the normal human immunological repertoire are low affinity antibodies that cross-react with other glycoconjugates carrying Galβ1-3GalNAc and probably do not have GM1-mediated biological activity. Other anti-GM1 IgM-antibodies with higher affinity and/or different fine specificity are present in patients with motor syndromes. Based on our studies of structural requirement for binding, we hypothesize that disease-associated anti-GM1 antibodies originate at random by mutations affecting the binding site of naturally-occurring ones. The hypothesis is conceptually similar to the established phenomenon of "genetic drift" in species evolutionary biology and is therefore termed "binding site drift".
KW - Anti-GM antibodies
KW - Antigen mimicry
KW - Autoimmune neuropathy
KW - Binding site drift
KW - Binding site expansion
KW - Gangliosides
UR - http://www.scopus.com/inward/record.url?scp=0036668812&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036668812&partnerID=8YFLogxK
U2 - 10.1023/A:1020232318647
DO - 10.1023/A:1020232318647
M3 - Article
C2 - 12374203
AN - SCOPUS:0036668812
VL - 27
SP - 687
EP - 695
JO - Neurochemical Research
JF - Neurochemical Research
SN - 0364-3190
IS - 7-8
ER -