Causes/Inheritance

Normally (A), the immune system releases antibodies to attack foreign invaders, such as bacteria. In autoimmune diseases (B), the antibodies mistakenly attack a person’s own tissues. In LEMS, they attack and damage muscle cells.

The immune system normally defends the body against diseases, but sometimes it can turn against the body, leading to an autoimmune disease. LEMS is one of many autoimmune diseases, which include arthritis and type 1 diabetes.

In all of these diseases, an army of immune cells that would normally attack bacteria and disease-causing "germs" mistakenly attacks cells and/or proteins that have essential functions in the body.

At the normal neuromuscular junction, a nerve cell tells a muscle cell to contract by releasing the chemical acetylcholine (ACh). ACh attaches to the ACh receptor — a pore or "channel" in the surface of the muscle cell — twisting it open and allowing an inward flux of electrical current that triggers muscle contraction. These contractions enable someone to move a hand, to dial the telephone, walk through a door or complete any other voluntary movement.

While myasthenia gravis (MG) targets the ACh receptors on muscle cells, LEMS interferes with ACh release from nerve cells.

Some 85 to 90 percent of people with LEMS test positive for antibodies against a protein called P/Q type voltage-gated calcium channel (VGCC). This protein is a pore that allows calcium entry into nerve cells, which is required for ACh release.

In cases where LEMS is associated with cancer, it's thought that the cancer cells inappropriately make VGCC, triggering the immune system to make anti-VGCC antibodies. The trigger for LEMS without cancer is unknown.

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