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Autoimmune pathophysiology of LEMS
What is the autoimmune pathophysiology involved in LEMS?
The primary antigen for the LEMS antibodies is found both at the presynapse and in small-cell carcinoma of the lung.
LEMS antibodies cross-react with N-type and L-type voltage-gated Ca 2+ channels and with synaptotagmin in the presynapse.
This decreases the number of voltage-gated Ca 2+ channels, which reduces activation of the cascade, thus leading to the release of fewer ACh vesicles.
Decreased ACh release decreases depolarization at the muscle endplate, and threshold for activation of the muscle fiber is not reached.
