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PQ Voltage Gated Calcium Channel Antibody

Voltage-gated calcium channel (VGCC) is a large transmembrane protein with multiple subunits that are named P, Q, N, L, T and R. P/Q channels play a role in release of acetylcholine from nerve endings, while N type channels are key components of the autonomic conduction system. P/Q-type VGCCs make up greater than 95 percent of the functioning receptors at the neuromuscular junction.

Lambert-Eaton myasthenic syndrome (LEMS) is an uncommon disorder of neuromuscular junction transmission that causes slowly progressive symmetrical proximal muscle weakness.  Autonomic dysfunction such as dry eyes, dry mouth, impaired sweating and erectile dysfunction may also be present. Early recognition is particularly important because approximately 50% of cases are associated with a malignancy, mainly small cell lung cancer.

Diagnosis of LEMS is confirmed by electrophysiology studies and testing for the presence of antibodies to voltage-gated calcium channel (VGCC). Antibodies against P/Q-type VGCC are present in approximately 85 to 95 percent of patients and antibodies against N-type VGCC are found in about 30 to 40 percent of patients with LEMS. Antibodies directed against VGCC interfere with the normal calcium flux required for the release of acetylcholine. Synaptic transmission fails when antibodies cause a critical loss of calcium channels.

A high titer P/Q-type VGCC antibody is strongly suggestive of LEMS in patients with a high pretest probability of LEMS. It is important to realize that P/Q-type VGCC antibodies are present in a variety of other diseases. Low tittered antibodies are present in some patients with myasthenia gravis, amyotrophic lateral sclerosis and other autoimmune diseases. They also may be detected in paraneoplastic disorders associated with lung, ovarian, or breast carcinoma. Thus, while the VGCC antibody test is confirmatory in patients with clinical and electrophysiologic features of LEMS, the antibody test alone is not diagnostic, especially in the presence of malignancy or amyotrophic lateral sclerosis.

Antibodies may not be present at onset of LEMS. Testing should be repeated later if clinical suspicion remains high. Titers are generally higher in patients with severe weakness, but severity cannot be predicted by antibody titer.

Calcium channel binding antibodies (IgG and IgM) are measured quantitatively by immunoprecipitation assays. Serum is the preferred specimen. However, antibody may be detected in cerebrospinal fluid when serum results are negative. If a spinal tap has been already been performed, it is recommended that CSF be submitted with serum and tested if serum is negative. 

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