The diagnosis of Lambert-Eaton myasthenic syndrome (LEMS) includes blood tests that can confirm the presence of autoantibodies against a protein called voltage-gated calcium channel (VGCC). Blood tests can confirm the results of other diagnostic tests such as electromyography (EMG).

Blood tests can also be performed to detect antibodies against a protein called SOX1, which is found in a large number of patients with LEMS associated with small-cell lung cancer (SCLC).

Antibodies in the blood of LEMS patients

Autoantibodies against VGCC can be detected in 85 to 90 percent of LEMS patients and 100 percent of patients with SCLC-associated LEMS. These antibodies against VGCC can also be detected in 3% to 5% percent of patients with SCLC who do not show symptoms of LEMS, such as muscle weakness or autonomic nervous system dysfunction. In approximately 10% to 15% of LEMS patients, autoantibodies against VGCC cannot be detected by blood tests.

Antibodies against SOX1 are specific markers for SCLC and can be used to identify LEMS patients with SCLC. They can be detected in 67 percent of patients.

The presence of these two antibodies in the blood can confirm the diagnosis of non-SCLC-LEMS and SCLC-LEMS, but negative results cannot be taken as confirmation of the disease being absent because it is possible that the levels of these antibodies are too low to detect.

How blood tests work to diagnose LEMS

In general, blood taken from a suspected LEMS patient is first centrifuged or filtered to separate the plasma  (the liquid part of the blood) from the blood cells. Then, small samples of plasma are subjected to experimental analysis to determine the presence of anti-VGCC and anti-SOX1 antibodies.

Anti-VGCC antibody detection

For the detection of anti-VGCC autoantibodies, a radioimmune assay (RIA) is performed. A small sample of plasma is mixed with a certain amount of a radioiodine-labeled human VGCC protein complex that is commercially available. If there is a detectable amount of anti-VGCC antibodies in the plasma sample, it binds to the radioiodine-labeled human VGCC protein complex and precipitates out of solution. This precipitate is then quantified based on comparison with experimental controls. If the anti-VGCC antibodies are absent or are present in very low amounts, they will not form a precipitate and the test will be negative.

Anti-SOX1 antibody detection

For the detection of anti-SOX1 antibodies in the blood, methods such as enzyme-linked immunosorbent assay (ELISA) or immunoblot are used.

In ELISA, recombinant human SOX1 protein is coated onto so-called ELISA plates and incubated with serum from the patient for a defined period of time to allow interaction and possible binding. The recombinant SOX1-antiSOX1 antibody interaction is detected and quantified. If anti-SOX1 antibodies are present in the blood plasma, a positive result will be obtained.

Anti-SOX1 antibodies can also be detected and quantified using an immunoblot method. The recombinant SOX1 protein is spotted on a membrane and then incubated with the patient’s serum sample. If the anti-SOX1 antibody is present in the serum, it will bind to the recombinant SOX1 protein on the membrane and form a complex that can be detected and quantified.

 

Last updated: July 25, 2019

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