Report: Use Multiple Tests to Find LEMS Antibodies
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Immunofluorescence, a technique that can be used to detect antibodies associated with Lambert-Eaton myasthenic syndrome (LEMS), was negative in a 72-year-old woman, but another technique — called immunoblot — was positive for LEMS-associated antibodies. This ultimately allowed for a LEMS diagnosis and the discovery of a previously unknown tumor.
According to researchers at the University Clinic Hospital of Valencia in Spain, these observations highlight the importance of combining multiple tests, rather than relying on a single one, to identify LEMS.
The team’s findings were described in the study, “Discordant SOX-1 antibodies results in paraneoplastic Lambert-Eaton syndrome diagnosis by the clinical laboratory,” published in the journal Clinical Biochemistry.
The 72-year-old woman was admitted to the hospital with complaints of progressive girdle weakness, which is weakness in the shoulders and hips. She described a sensation of heaviness in her legs that led to instability while walking, and said symptoms had started some four or five months earlier.
Electromyography — a technique that ca be used to assess the electrical activity of muscle cells — revealed several abnormalities, but laboratory tests indicated her blood parameters, liver and kidney function were all within normal limits.
Collectively, these findings led to a suspicion of an autoimmune myopathic disorder, a condition in which the immune system wrongly launches an attack on healthy tissue, causing muscle dysfunction. This suspicion led the patient’s care team to test for antibodies that are characteristic of these diseases.
To do so, the team used a technique called immunofluorescence. This technique involves using a fluorescent molecule that binds to a specific antibody of interest, allowing researchers to assess the antibody’s presence in a sample. However, immunofluorescence testing came back negative for all tested antibodies.
The team then conducted another series of tests using a different method called immunoblotting. Immunoblotting and immunofluorescence are somewhat similar in concept, since both rely on molecules that specifically bind to an antibody of interest. But in immunoblot, additional steps are taken to separate proteins by size and immobilize them on a membrane, prior to visualization.
Immunoblotting revealed that the patient was positive for antibodies against SOX-1 — a type of antibody that is found commonly in people with paraneoplastic LEMS, meaning LEMS that develops in association with cancer.
Further workup revealed that, indeed, the patient had small cell lung cancer — the type of cancer most commonly associated with LEMS.
“Although this pattern was not evident in [immunofluorescence] images in our patient sample, SOX-1 autoantibodies were detected with immunoblot,” the researchers wrote.
“Considering only the [immunofluorescence] result could have resulted in false negative results, and immunoblot was particularly helpful in detecting the tumor,” they wrote.
They added that these findings highlight “the importance of combining several methodologies rather than relying solely upon [immunofluorescence] when paraneoplastic neurological syndromes are highly suspected.”
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