"Ganglioside antibodies, extended" profile

Gangliosides are glycospholipids containing a sialic acid residue. They occur in the membrane of many cells, but are particularly high in neurons. They are essential for cell growth and differentiation, nerve impulse transmission, and immune reactions. Some neurological diseases are accompanied by the production of autoantibodies to gangliosides. These antibodies are most commonly found in Guillain-Barré syndrome.

Guillain-Barré syndrome is an acute autoimmune disease characterised by peripheral nerve damage. In the vast majority of cases, the disease develops 2-4 weeks after an acute respiratory or intestinal infection. Infective agents associated with it include: Campylobacterjejuni (C. jejuni), Epstein-Barr virus, cytomegalovirus, Mycoplasmapneumoniae, hepatitis B virus, human immunodeficiency virus and some others. The protective antibodies produced against these pathogens also bind to the gangliosides of their own cell membranes. This "molecular mimicry" phenomenon is the main pathophysiological mechanism of the disease. C. jejuni infection plays a major role in the development of Guillain-Barré syndrome. The lipooligosaccharide of C. jejuni has significant antigenic similarity to the gangliosides GM1 and GD1b. Autoantibodies to gangliosides are regarded as specific markers for Guillain-Barré syndrome in laboratory diagnosis.

Autoantibodies to gangliosides are detected in 60% of patients with Guillain-Barré syndrome. Therefore, a negative test result does not completely rule out the disease.

Autoantibodies to GM1 and GD1b gangliosides are the most frequently detected autoantibodies. The clinical picture of the syndrome is heterogeneous and depends on the presence of autoantibodies to different antigens. There are several variants of the syndrome. In the vast majority of cases, the classical form is an acute inflammatory demyelinating polyradiculoneuropathy accompanied by segmental loss of myelin in the peripheral fibers and manifested by pain, paresthesias and paresis of the proximal muscle groups of the lower and then upper extremities (ascending paralysis). Muscle weakness develops acutely and can lead to paralysis of all limbs within a few days. Autoantibodies to ganglioside GD1b are the most frequently detected autoantibodies in the blood of these patients. The presence of autoantibodies to ganglioside GD1b is also associated with the development of severe coordination and balance disorders (sensory or cerebellar ataxia). The highest concentration of GD1b ganglioside has been found in the membrane neurons of the sensitive spinal ganglia, which explains the ataxia in the presence of autoantibodies to this ganglioside. In 40% of cases of acute inflammatory demyelinating polyradiculoneuropathy, antibodies to C. jejuni are detected.

Another clinical variant of the syndrome, acute motor axonal neuropathy, is characterised by predominant damage to motor axons of nerve fibres while myelin, sensitivity and cranial nerve function remain intact. This variant of the syndrome is more common in children. Ganglioside GM1 is considered to be the main antigen of this disease. Autoantibodies directed against GM1 ganglioside initiate axolemmal damage as well as blocking potential-dependent calcium channels. A particular feature of this clinical variant is the presence of hyperreflexia (in contrast to the "classical" variant of the syndrome, which is hyporeflexia). Hyperreflexia is associated with autoantibodies to GM1 ganglioside. Antibodies to C. jejuni are found in 75% of these patients.

Ganglioside GQ1b is a major antigen in Miller-Fisher syndrome, a variant of Guillain-Barré syndrome. Autoantibodies to GQ1b initiate and maintain an inflammatory response leading to the destruction of myelin. The clinical picture is due to the fact that the highest concentration of GQ1b ganglioside is found in the myelin sheath of the cranial nerves innervating the eyeball muscles and in some large nerve trunks of the extremities. The most specific test to confirm the diagnosis of Miller-Fisher syndrome is a blood test for autoantibodies to GQ1b ganglioside.

It should be noted that it is often possible to detect a combination of different autoantibodies to gangliosides in the blood of patients with different clinical forms of the syndrome.

Normally, neurological deficits in Guillain-Barré syndrome fully recover within 6-12 months. The test result becomes negative in the recovery period, but in 7-15% of patients neurological deficits persist for life. Persistent detection of autoantibodies to GM1 ganglioside is associated with a longer period of recovery.

Non-infectious diseases (systemic lupus erythematosus) and blood cancers (especially Hodgkin's lymphoma) may also contribute to autoimmune neuropathy. For this reason, if autoantibodies to gangliosides are positive and the diagnosis of Guillain-Barré syndrome is confirmed, additional general clinical tests are advisable. In addition, additional laboratory tests are recommended to rule out other more common causes of peripheral neuropathy (vitamin B12 deficiency, diabetic neuropathy, hypothyroidism).