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Neuropathy Associated Antibodies

Polyneuropathy is a disorder involving multiple large peripheral nerve fibers, usually bilaterally. Symptoms range from numbness and tingling in the feet and hands to varying degrees of muscle weakness, ataxia and autonomic dysfunction. The causes of polyneuropathy include diabetes, infections, toxicities, vitamin B12 deficiency and autoimmune diseases. Autoantibodies recognizing neurologic tissue antigens have been associated with peripheral sensory, motor, and sensorimotor neuropathies. Neurologic autoantibodies also occur in some patients with cancer, producing a variety of paraneoplastic syndromes (See Paraneoplastic Antibody).

Immune mediated peripheral neuropathy can be acute or chronic and can result in either axonal degeneration or demyelination. The antibodies can either be associated with monoclonal gammopathies or inflammatory disorders. In the latter case, the antibodies are polyclonal. Inflammatory polyneuropathies include Guillain-Barre syndrome (GBS), chronic inflammatory demyelinating polyneuropathy (CIDP), GALOP (gait disorder, autoantibody, late age onset, polyneuropathy) syndrome, and multifocal motor neuropathy (MMN). GBS is acute in onset, while CIDP is chronic and progressive.

Ganglioside antibodies

Gangliosides are a group of glycosphingolipids widely distributed in membrane components of the nervous system. They possess a common long chain fatty acid, but exhibit distinctive carbohydrate moieties containing one or more sialic acid residues. Ganglioside nomenclature is defined by the following scheme:

  • G refers to ganglio
  • M, D, T, and Q refer to the number of sialic acid residues (mono, di, tri, and quad)
  • Numbers and lower case letters refer to the sequence of migration on thin layer chromatography (TLC)

Thus, both GD1a and GD1b express two sialic acid residues, but show subtle differences in TLC migration patterns, allowing their separation into 1a and 1b.

The gangliosides most commonly recognized by neuropathy associated autoantibodies are GM1, asialo-GM1, GD1a, GD1b, and GQ1b.

Detection of GM1 antibody, usually of the IgM isotype, is associated with multifocal motor neuropathy and lower motor neuropathy, characterized by muscle weakness and atrophy. The GM1 IgM may be present as a monoclonal IgM paraprotein or as polyclonal IgM. Polyclonal GM1 IgG may also be detected in patients with motor neuropathy.

GM1 antibodies of the IgG and IgA isotypes may be found in association with amyotrophic lateral sclerosis (ALS), as well as Guillain-Barré syndrome (GBS) following

Campylobacter jejuni infection. GM1IgA may be the only GM1 antibody isotype found in approximately 20% of GBS patients. Recovery is slower and less complete in these patients compared to patients without GM1 IgA.

Antibodies recognizing GD1a, GD1b, and asialo-GM1 are found in association with motor and sensorimotor neuropathies, as well as ALS and GBS.

Of all the ganglioside antibodies studied, those recognizing GQ1b show the strongest disease association; GQ1b antibodies are found in more than 90% of patients with Miller Fisher Syndrome, characterized by ataxia, areflexia, and ophthalmoplegia. GQ1b antibodies are also found in GBS patients with ophthalmoplegia, but not in GBS patients without ophthalmoplegia.

Individual patients may possess antibodies to a single ganglioside or to multiple gangliosides. A panel assessing antibody reactivity to multiple gangliosides is thus recommended to maximize detection of neuropathy-associated ganglioside antibodies.

Myelin-associated glycoprotein antibodies

Myelin-associated glycoprotein (MAG) is a constituent of peripheral and central nervous system myelin. High titer IgM antibodies to MAG are associated with sensorimotor demyelinating peripheral neuropathy. Sensory symptoms tend to dominate early in disease, with motor symptoms occurring later. MAG antibodies are usually associated with the presence of an IgM monoclonal protein; approximately 50% of patients with IgM monoclonal gammopathies and associated peripheral neuropathies have detectable MAG antibodies.

Patients with sensory neuropathy may have MAG antibodies at low titers, usually in association with high titers of sulfatide antibodies. MAG antibodies at moderate titers have also been reported in multiple sclerosis and inflammatory neuropathies.

In general, antibodies recognizing MAG react with a carbohydrate determinant that is also present on an acidic glycolipid, sulfoglucuronyl paragloboside (SGPG). Initial assays for MAG antibody utilized SGPG as the target antigen. However, a recent study of 18 patients with sensorimotor demyelinating neuropathy identified 2 patients with antibodies recognizing the whole MAG protein but not SGPG, and 1 patient with antibodies recognizing SGPG but not the MAG protein (15 patients had antibodies recognizing both SGPG and MAG). Based on these findings, some laboratories now perform two separate ELISA procedures, one utilizing SGPG as antigen and one utilizing MAG as antigen, to maximize detection of MAG antibodies. Further, for increased specificity, specimens giving a positive result in either ELISA are automatically tested with a confirmatory MAG antibody Western blot assay.

Sulfatide is a glycolipid found in greatest quantity in the CNS and peripheral nerve myelin. Antibodies against sulfatide are associated with Guillain-Barre syndrome (GBS), chronic inflammatory demyelinating polyneuropathy (CIDP), sensory neuropathy and sensorimotor neuropathy.





Multifocal or lower motor



Motor & sensorimotor



Motor & sensorimotor



Sensory w/ or w/o ataxia



Motor & sensorimotor

Miller Fisher Syndrome


Sensory & demyelinating



Sensory & sensorimotor


SAN = sensory ataxic neuropathy, AMAN = acute motor axonal neuropathy, CANOMAD = chronic ataxic neuropathy

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