Antiganglioside Antibody Syndrome

Antiganglioside antibody syndrome (ASS) is a condition caused by anti-ganglioside antibodies (AGAs) that react with self-gangliosides. Gangliosides are essential for proper cell signaling, transduction and influence neuroplasticity, all of which are affected by autoimmune mediated damage. AGAs are implicated in many autoimmune mediated peripheral neuropathies such as acute and chronic polyradiculoneuropathies. Acute immune-mediated polyradiculoneuropathies encompass Guillain-Barre syndrome (GBS) and its variants. Chronically occurring ones include multifocal motor neuropathy (MMN) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP).

Guillain-Barré syndrome (GBS)

The antiganglioside antibody syndrome is most commonly associated with Guillain-Barré syndrome (GBS), which is an acute immune-mediated polyradiculoneuropathy that can cause acute quadriplegia. Infection with micro-organisms, including Campylobacter jejuni (C. jejuni), Haemophilus influenzae, and Cytomegalovirus (CMV), is recognized as a main triggering event for the disease. Lipooligosaccharide (LOS) genes are responsible for the formation of human ganglioside-like LOS structures in infectious micro-organisms that can induce GBS. Anti-GM1 antibody is commonly associated with a pure motor variant of GBS. Anti-GM2 IgM is linked to severe GBS following a CMV infection.

Fig. 1 Origin and contribution of antiganglioside antibodies and C. jejuni infection to GBS

Pathogenic Role of Antiganglioside Antibodies

The pathogenic mechanism of AGAs in antiganglioside antibody syndrome involves autoimmune attack on peripheral nerves, leading to inflammation, demyelination, and impairment of nerve function. Binding of AGAs to gangliosides on axonal membranes, nodes of Ranvier, myelin sheath components, Schwann cells, neuromuscular junctions or other neural cell surfaces may elicit inflammatory damage through complement-dependent and independent mechanisms, resulting in nerve conduction blocks and subsequent axonal degeneration. Other effects of AGAs include: disrupting the axonal cytoskeletal architecture, disrupting nodal and paranodal channels, and destabilizing the membrane. In addition, experimental data has revealed that AGAs in vitro can disrupt the integrity of the blood nerve barrier (BNB), possibly foreshadowing a similar effect on the blood brain barrier (BBB).

Fig.2 The mechanism involved in the pathogenesis of GBS and MFS

Laboratory tests

Ganglioside antibody measurements are useful both in confirming diagnosis and in refining classification. Different ELISA methods, blot techniques, and immunochromatographic procedures can be used. The proper assay conditions are important because anti-glycolipid antibodies often bind to their targets with low avidity. False negative results occur if assay methodology fails to preserve the antibody-antigen bond or generates a low signal-to-noise ratio. Several methodological steps seem to improve the reliability of the enzyme-linked immunosorbent assay (ELISA) techniques that are commonly utilized for particular anti-ganglioside antibody measurements. The sensitivity of the assay is increased by taking measures to preserve the antigen-antibody bond. These include incubation for a longer time (at least 4 hours), conducting the assay at 4° C, and avoiding the use of detergent in washing buffers. The specificity of the ELISA assay is improved by using human serum albumin or normal goat serum instead of bovine serum albumin to block non-specific binding sites in wells. Human serum occasionally has antibody activity to bovine serum albumin and can produce false positive or negative results depending on the type of controls used.