Diagnostic Tests

CLINICAL ASSOCIATIONS

Mitogen’s Neurological Disease Profile assay is an autoimmune diagnostic test that detects both IgG and IgM autoantibodies to GM1, GM2, GM3, GD1a, GD1b, GT1b, and GQ1b. Antibodies against the Monosialoganglioside GM1 are associated with multifocal motor neuropathy (MMN) with a prevalence of 40-70%. These antibodies are in most cases of class IgM/IgG. Furthermore, elevated antibody titers against the monosialoganglioside GM1 occur in 22-30% patients with Guillain-Barré syndrome. The titer correlates with disease activity: In the acute phase the titer increases to a maximum value and decreases during the disease. Antibodies against the Disialoganglioside GD1b have been described in rare cases of patients with sensory neuropathy. Antibodies against the Tetrasialoganglioside GQ1b can be detected in more than 90% of the patients with Fisher syndrome.

The antigen targets in this autoimmune assay belong to the family of gangliosides – complex molecules that contains both lipids (fats) and carbohydrates (sugars). Gangliosides are present in all tissues and body fluids, but are most abundantly expressed in the nervous system. In cells, gangliosides are most often present in plasma membranes. Hence their function includes cell-cell recognition, cellular adhesion and signal transduction.

GM1, the first ganglioside discovered, has important physiological properties and impacts neuronal plasticity and repair mechanisms. GM1 is also involved in the release of neurotrophins in the brain.
GM2 was the second monosialic ganglioside discovered. It is associated with GM2 gangliosidoses such as Tay–Sachs disease.
GM3 is the most common membrane-bound glycosphingolipid in tissues that functions in cellular signaling as well as inhibition of cell growth (inhibition of growth factor receptors) and cytokine production.
GD1a and GD1b (along with GM1) comprise the majority of gangliosides in the brain.
GQ1b plays a role in synaptic plasticity and cognition.

References:
Mocchetti I (2005). “Exogenous gangliosides, neuronal plasticity and repair, and the neurotrophins”. Cell. Mol. Life Sci. 62 (19–20): 2283–94. doi:10.1007/s00018-005-5188-y. PMID 16158191.
Guetta E, Peleg L (2008). “Rapid Detection of Fetal Mendalian Disorders: Tay–Sachs Disease”. Methods Mol. Biol. 444: 147–59. doi:10.1007/978-1-59745-066-9_11. PMID 18425478.
Chan RB, et al. (2017-02-17). “Elevated GM3 plasma concentration in idiopathic Parkinson’s disease: A lipidomic analysis”. PLOS ONE. 12 (2): e0172348. Bibcode:2017PLoSO..1272348C. doi:10.1371/journal.pone.0172348. PMC 5315374. PMID 28212433.
Tsukuda Y, et al. (2012-06-29). Rojas M (ed.). “Ganglioside GM3 has an essential role in the pathogenesis and progression of rheumatoid arthritis”. PLOS ONE. 7 (6): e40136. doi:10.1371/journal.pone.0040136. PMC 3387008. PMID 22768242.
Sturgill E, et al (2012-06-26). “Biosynthesis of the major brain gangliosides GD1a and GT1b”. Glycobiology. 2012 Oct; 22(10): 1289–1301. PMID: 22735313
Shin MK, Ch oi MS, et al. (2019) “Ganglioside GQ1b ameliorates cognitive impairments in an Alzheimer’s disease mouse model, and causes reduction of amyloid precursor protein”. Scientific Reports. 2019 Jun.