Test Id : GAES

Screening tests are performed for IgG and IgM antibodies to gangliosides GM1 and GD1b. If positive, the appropriate titer will be performed at an additional charge.

For more information see:

-Ganglioside Antibody Panel Algorithm.

-Acquired Neuropathy Diagnostic Algorithm

Patient Preparation: For optimal antibody detection, specimen collection is recommended to occur prior to initiation of immunosuppressant medication or intravenous immunoglobulin treatment.

Supplies: Sarstedt Aliquot Tube, 5 mL (T914)

Collection Container/Tube:

Preferred: Red top

Acceptable: Serum gel

Submission Container/Tube: Plastic vial

Specimen Volume: 1 mL

Collection Instructions: Centrifuge and aliquot serum into a plastic vial.

• Ganglioside Antibody Panel Algorithm
• Acquired Neuropathy Diagnostic Algorithm

If not ordering electronically, complete, print, and send a Neurology Specialty Testing Client Test Request (T732) with the specimen.

0.5 mL

Supporting the diagnosis of an autoimmune neuropathy

Screening tests are performed for IgG and IgM antibodies to gangliosides GM1 and GD1b. If positive, the appropriate titer will be performed at an additional charge.

For more information see:

-Ganglioside Antibody Panel Algorithm.

-Acquired Neuropathy Diagnostic Algorithm

Neuropathy patients have variable sensory disturbance (loss or exaggerated sensation including with pain), weakness, and autonomic involvements (sweat abnormalities, gastrointestinal dysfunction, and lightheadedness on standing). These symptoms are a result of injury to the distal nerves, roots, and ganglia or their gathering points (nerve plexus in the thighs and arms). Patients may have symmetric or asymmetric involvement of the extremities, trunk, and head, including extraocular muscles. Subacute onsets and asymmetric involvements favor inflammatory or immune causes over inherited or metabolic forms. Depending on the specific inflammatory or immune-mediated causes, other parts of the nervous system may also be affected (brain, cerebellum, spinal cord). Nerve conduction studies and needle electromyography can help classify the neuropathy as primary axonal, primary demyelinating, or mixed axonal and demyelinating.

Among the immune-mediated peripheral neuropathies, autoantibodies to gangliosides represent an important class of noncancer-associated autoimmune peripheral neuropathies. Gangliosides are glycosphingolipids that contain sialic acid and are present in many cell types, most abundantly within neural tissues along their linings (myelin). Depending on the specific ganglioside autoantibody found and the antibody titer, in the appropriate clinical context these findings may be supportive of a specific clinical diagnosis and may also be prognostic for treatment response.(1,2)

Specifically, in multifocal motor neuropathy (MMN) and multifocal acquired demyelinating sensory and motor (MADSAM) neuropathy, also known as Lewis-Sumner syndrome or multifocal chronic immune demyelinating polyradiculoneuropathy, the presence ganglioside autoantibodies, particularly high-titer GM1 IgM autoantibodies, may be supportive of the diagnosis in the correct clinical context. Furthermore, ganglioside seropositivity has been associated with favorable response to immunotherapy among patients suspected to have MMN during the initial clinical evaluation.(1)

Additionally, the presence of ganglioside antibodies may support a diagnosis of Guillain-Barre syndrome (GBS) in the appropriate clinical context.(3) GBS is a class of autoimmune peripheral neuropathies that comprises a spectrum of disorders, including acute inflammatory demyelinating polyradiculoneuropathy, acute motor axonal neuropathy, and acute motor and sensory axonal neuropathy. This class of autoimmune neuropathies is generally characterized by an acute onset. Although the diagnosis of these disorders is dependent on clinical evaluation and electrophysiologic studies, assessment of ganglioside antibodies can further support the diagnosis.

GQ1b-IgG ELISA: Negative

IgG Disialo. GD1b: Negative

IgM Disialo. GD1b: Negative

IgG Monos. GM1: Negative

IgM Monos. GM1: Negative

IgG Disialo GD1b Titer: <1:2000

IgM Disialo GD1b Titer: <1:2000

IgG Monos GM1 Titer: <1:2000

IgM Monos GM1 Titer: <1:4000

High titers (>1:8000) favor the diagnosis of multifocal motor neuropathy or multifocal acquired demyelinating sensory and motor (MADSAM) neuropathy over motor neuron disease. About 30% to 50% of patients with these clinical syndromes or the pure motor variant of chronic inflammatory demyelinating polyneuropathy have ganglioside autoantibodies. High-antibody titers appear to be a specific, but not sensitive, marker of these related disorders.

Positive titer values less than 1:16,000 may be found in motor neuron disease, monoclonal gammopathy of uncertain significance, and healthy individuals. High titers are very specific of an autoimmune neuropathy.

This test is not diagnostic and should be interpreted in the appropriate clinical context.

This test does not include testing for ganglioside GD1a autoantibodies.

1. Martinez JM, Snyder MR, Ettore M, et al. Composite ganglioside autoantibodies and immune treatment response in MMN and MADSAM. Muscle Nerve. 2018;57:1000-1005. doi:10.1002/mus.26051

2. Taylor BV, Gross L, Windebank AJ. The sensitivity and specificity of anti-GM1 antibody testing. Neurology. 1996;47:951-955

3. Kaida K, Ariga T, Yu RK. Antiganglioside antibodies and their pathophysiological effects on Guillain-Barre syndrome and related disorders-a review. Glycobiology. 2009;19:676-692. doi:10.1093/glycob/cwp027

Ganglioside Antibodies IgG/IgM Disialo, GD1b; IgG/IgM Monos, GM1 Enzyme-Linked Immunosorbent Assays:

Antiganglioside antibodies are detected by enzyme-linked immunosorbent assays (ELISA). Microwells are precoated with GM1 or GD1b antigen. The calibrator, controls, and diluted patient samples are added to the wells, and autoantibodies recognizing GM1 or GD1b bind during the first incubation. After washing the wells to remove all unbound proteins, purified alkaline phosphatase-conjugated antihuman IgG or IgM is added. The conjugated secondary IgG or IgM binds to the captured human autoantibody, and the excess unbound conjugated IgG or IgM is removed by a further wash step. The bound conjugated IgG or IgM is visualized with 4-nitrophenyl phosphate substrate, which gives a yellow reaction product, the intensity of which is proportional to a concentration of autoantibody in the sample. A base is added to each well to stop the reaction, and the final product is read at 405 nm. For screening assays, patient results are calculated by dividing the optical density (OD) of patient samples or controls by the average OD of the calibrator. Any sample with a ratio of patient to calibrator OD greater than 2.0 is considered positive. Any positive sample on screening is then titered. For titer assays, patient samples are diluted and the last dilution where the ratio of patient to calibrator OD greater than 2.0, is reported as the end-point titer.(Unpublished Mayo method)

Ganglioside GQ1b Antibody IgG ELISA:

Microwells are precoated with GQ1b antigen. The calibrator, controls, and diluted patient samples are added to the wells, and autoantibodies recognizing GQ1b bind during the first incubation. After washing the wells to remove all unbound proteins, purified horseradish peroxidase-labeled anti-human IgG conjugate is added. The conjugated IgG binds to the captured human autoantibody, and the excess unbound conjugated IgG is removed by a further wash step. The bound conjugated IgG is visualized with 3,3',5,5'-tetramethylbenzidine substrate, which gives a blue reaction product, the intensity of which is proportional to a concentration of autoantibody in the sample. Acid is added to each well to stop the reaction. This produces a yellow end-product color, which is read at 450 nm. Patient results are calculated as a cutoff index (COI) by dividing the OD of patient samples or controls by the average OD of the calibrator. Any sample with a COI greater than or equal to1.0 is considered positive. Any sample with a COI less than 1.0 is considered negative. Results are reported qualitatively as positive or negative.(Unpublished Mayo method)

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This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. It has not been cleared or approved by the US Food and Drug Administration.

83516 x5

83520 x4 (if applicable)