Gangliosides, SGPG (glycosphingolipids) and MAG (glycoprotein) are important components of neuronal cell membranes of both, the peripheral and central nervous system. Different antibodies targeting these structures have been found which can cause autoimmune neuropathies. Anti-ganglioside antibodies can provide better understanding and practical information about the pathophysiology of peripheral neuropathies (23, 24).
While many neural antibodies have been described, only a few of them are diagnostically relevant in specific peripheral neuropathies. BÜHLMANN was one of the first companies who made anti-ganglioside, -MAG and -SGPG antibody IVD tests commercially available and offered such tests to the market.
We are regarded as experts in this field of study and provide a package of sensitive and high quality standardized IVD ELISAs.
Anti-ganglioside antibodies: descriptions
Different anti-ganglioside antibodies are associated with different neuropathies. Anti-GM1 and -GD1b antibodies have been described for the first time in 1986 in a patient with a motor neuron disease (1, 2, 3, 4). In 1990, IgG type anti-GM1 antibodies were identified in patients with acute axonal polyneuropathies (5, 6, 7). First descriptions followed with GQ1b antibodies as specific marker for the Miller-Fisher Syndrome (6) and GD1a antibodies for axonal neuropathies (7).
In 2001, antibodies against glycosphingolipids with two sialic (disialosyl) acids (e.g. GQ1b and GD1b) have been described in the context of chronic ataxic neuropathies (14). Associations of other antibodies (e.g. GM2-antibodies) are less clear but are described in the context of cytomegalovirus (CMV)-induced Guillain-Barré syndrome (GBS; 12, 13). The associations between anti-glycolipid antibodies and inflammatory neuropathies are described in a large collection of literature whereas only limited data for antibodies against other glycolipids exist.
Basically, it is the set of IgG and IgM type anti-ganglioside antibodies (table 1) which are associated with peripheral neuropathies. They facilitate the diagnosis of both, acute and chronic immune neuropathies.
Table 1: Neural antigens and clinical correlates; abbreviation: CANOMAD: chronic ataxic neuropathy ophthalmoplegia IgM agglutinins disialosyl antibodies
Anti-MAG and -SGPG antibodies
Reports in the early 80-ies describe neurological manifestations of monoclonal antibodies and distinct clinical syndromes which are associated with particular anti-MAG antibody specificities (15, 16). Ever since, a large bulk of papers have demonstrated the pathogenic role of these antibodies.
The IgM antibodies in most affected patients with neuropathies react with the oligosaccharides (HNK-1-epitope) of glycolipids and glycoproteins that are concentrated in the peripheral nerves. A small molecular weight HNK-1 mimetic has been chemically synthesized in 2015 and the relevance of HNK-1 antibodies against the minimal HNK-1 epitope was shown in 2019 (19, 20, 21, 22).
Anti-Ganglioside Antibody IVD test Development
BÜHLMANN has been at the forefront of neuroimmunology test development for roughly a third of a century, combining innovation with commitment to high quality standards. The first IVD anti-ganglioside antibody ELISA assay was launched soon after studies demonstrated associations of anti-GM1 and -GD1b antibodies and acute and chronic neuropathies. Thereafter, BÜHLMANN generated a range of IVD ELISA tests for peripheral neuropathies. Key steps of the development of neuroimmunology ELISAs by BÜHLMANN are presented in the timeline below.
Today, we offer a broad portfolio of IVD ELISA tests with the GanglioCombi™ MAG ELISA combining MAG and gangliosides on the same microtiter plate. The GanglioCombi™ Light ELISA offers to test the three most relevant and frequent gangliosides GD1b, GQ1b and GM1. With our anti-MAG antibody ELISA test we provide an assay characterized by an outstanding sensitivity and specificity which is referred as gold standard by many Neurologists and Laboratories to reliably quantify anti-MAG antibodies in immune-mediated demyelinating neuropathies. Further we offer an anti-SGPG ELISA which enhances the chance to detect all IgM-related neuropathies and an anti-GM1 ELISA which allows individual testing of anti-GM1 antibodies of the IgG and/or the IgM isotype.