Myelin Associated Glycoproteins (MAG) Antibodies

Peripheral neuropathies, autoimmune responses of the peripheral nervous system, are associated with autoantibodies against various neural glycoconjugates. Neuropathies associated with anti-MAG with IgM paraproteinemia are often slowly progressive with evidence of demyelination and a variable degree of axonal loss associated with gait ataxia. 50% of all peripheral neuropathy cases with IgM paraproteinemia possess anti-MAG
antibodies. Detection of anti-MAG autoantibodies is useful for the clinician, as it suggests active demyelination in a peripheral neuropathy.

Immunofluorescence is a sensitive method for the screening and detection of anti-nerve myelin associated proteins and ganglioside autoantibodies.

Pareneoplastic Syndromes

Neuronal Antibodies

Autoimmune responses of the central nervous system (CNS), recognized as paraneoplastic neurologic disorders are manifestations of an antitumor immune response. The following autoantibodies are found in paraneoplastic syndromes:

• anti-Hu, type I anti-neuronal nuclear antibody (ANNA-1), is associated with small cell lung cancer resulting in paraneoplastic encephalomyelitis (PE).

• anti-Yo, anti-purkinje cell antibodies (PCA-1), is associated with ovarian and breast carcinomas resulting in paraneoplastic cerebellar degeneration (PCD).

• anti-Ri, type II anti-neuronal nuclear antibody (ANNA-2), is associated with neuroblastoma (children) and fallopian or breast cancer (adults) resulting in paraneoplasticopsoclonus myoclonus ataxia (POMA).

These markers help in discriminating between true paraneoplastic disorders and other inflammatory disorders of the nervous system that mimic a paraneoplastic syndrome. IFA provides a sensitive method of detecting these auto antibodies. Anti-Hu/anti-Ri auto antibodies, which characteristically stain the granular cell nucleus, are easily distinguished from the Purkinjee cell cytoplasm staining anti-Yo antibodies.

Motor-Neuron disorders (neuropathies) can be debilitating or fatal if they affect vital organ functions. Neuropathic syndromes are often difficult to diagnose as they may have similar symptoms.

Neuropathies can be hereditary, infectious or autoimmune in nature. Some neuropathies, such as Guillain-Barré Syndrome (GBS), are more completely characterised than others. GBS is an acute, inflammatory autoimmune disorder characterised by limb weakness, loss of tendon reflex, sensory dysfunctions and poor prognosis.

Patients exhibiting neuropathies elicit antibodies to gangliosides, acidic glycosphingolipids localised in the outer layer of plasma membranes. These antibodies may be directed against GM1, Asialo GM1, GD1a, GD1b, GQ1b, sulfatides and/or galactocerebroside. More than two thirds of GBS patients with GM1 antibodies have had a prior infection mediated by a virus or bacteria. 

GQ1b is a minor component of gangliosides in both the central and peripheral nervous system. GQ1b antibodies occur in Miller Fisher syndrome (MFS), a variant of GBS. Symptoms consist of ophthalmoplegia, ataxia and areflexia and often follow an infectious episode similar to GBS. Since they are absent in closely related neuropathies like GBS, they represent a specific indicator for MFS.

Treatment of patients with neuropathies involves plasma exchange. This procedure can be effective provided it is initiated within two weeks of onset of symptoms. Therefore, diagnostic tests based on the early detection of auto antibodies are a valuable complement to such therapies.