| Objective: Gangliosides, sialic acid-containing glycosphingolipids highly enriched in the vertebrate nervous system have yet to be fully defined, they are thought to mediate neural cell to cell recognition, neural tissue developing, synapse introduction and modulate intracellular signaling Gangliosides are also implicated in various neural disorders, Anti-ganglioside antibodies are associated with some immune mediated neuropathies. The mechanism could be: The C. jejuni lipopolysaccharide LPS fraction contains side chains with the same structures as some of thegangliosides, in particular gangliosides, such raise the antibody against ganglioside. Several associations between anti-ganglioside specificity and clinical features are emerging. For instance, IgG anti-GD1a and -GM1 are associated with predominant motor axonal injury in the acute motor axonal (AMAN) variant of GBS, The clinical phenotype associated with anti-GD1b antibodies is sensory ataxic neuropathies and Fisher syndrome associated with GQ1b. One conflict is that antibodies recognizing ubiquitous gangliosides are associated with clinical symptoms that imply specific cellular injury, for example motor axons in AMAN. Further, gangliosides are present in both axons and myelin, with no significant quantitative differences between major gangliosides in human ventral and dorsal roots to explain the different ganglioside associations with primary axonal injury or predominant motor or sensory fiber damage. The best option is to use patient serum to localize the ganglioside In nerve tissue. But immunolocalization studies with patient sera or with affinity purified patient antibodies would help experimentally address the issue of the selective nerve fiber injury associated with anti-ganglioside antibodies. However, patients' sera cannot be used reliably in localization studiesbecause antibodies in normal sera bind to peripheral nerves, and affinity purification techniques for anti-glycolipid antibodies are inefficient. Previous localization studies including our own, mostly in the context of anti-GM1 antibodies, are limited by the use of low affinity usually IgM anti-ganglioside antibodies or bacterial toxins and lectins. These reports do not clarify the basis of preferential damage to certain nerve cells and nature of the target antigens; however, the properties of these reagents are quite different from those of IgG anti-ganglioside antibodies usually detected in patients with GBS. In the absence of experimentally useful human anti-ganglioside antibodies, high-affinity IgG-class mouse anti-ganglioside mAbs with well-defined specificities similar to those found in GBS would be useful in probing the pathogenetic sequence of this disease. Gangliosides, glycosphingolipids bearing one or more sialic acid residues, are expressed in all vertebrate tissues, and variation in the sugar composition and sequence gives rise to dozens of distinct ganglioside structures. Raising antibodies against these determinants has been a challenge. Many anti-ganglioside mAbs have been reported, but there are few high affinity IgG antibodies against major brain gangliosides, only IgM antibody. IgM antibody is not as good as IgG in research. We demonstrated that wild type mice injected with a multivalent GD1a immunoconjugate (GD1a-KLH) mounted only a weak IgM response and no IgG response. We speculated that wild type mice, which express major gangliosides, have anergic or deleted ganglioside-reactive T-cell clones and therefore can not mount a vigorous humoral immune response against "self" gangliosides. Advances in ganglioside metabolism and genetics provides a solution to this problem. These mice were engineered to carry a deletion in the gene coding the ganglioside-specific glycosyltransferase UDP-GalNAc:GM3/GD3 4-N-acetylgalactosaminyltransferase (GM2/GD2 synthase) as described previously . The resulting gene-deleted mice failed to express the major brain gangliosides GM1, GD1a, GD1b or GT1b, instead expressing GD3 and GM3. This approach permits, for the first time, |
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