Neuromuscular Autoimmunities

Autoimmunities of the Endocrine Glands

On occasion, the thyroid gland is the target of autoimmunity. The underlying cause of Graves’ disease is the attachment of autoantibodies to receptors on the follicle cells that secrete the hormone thyroxin. The abnormal stimulation of these cells causes the overproduction of this hormone and the symptoms of hyperthyroidism. In Hashimoto’s thyroiditis, both autoantibodies and T cells are reactive to the thyroid gland, but in this instance, they reduce the levels of thyroxin by destroying follicle cells and by inactivating the hormone. As a result of these reactions, the patient suffers from hypothyroidism.

The pancreas and its hormone, insulin, are other autoimmune targets. Type I diabetes mellitus is caused by a dysfunction in insulin production by beta cells in the pancreas or its utilization by cells. This form is associated with autoantibodies and sensitized T cells that damage the beta cells. A complex inflammatory reaction leading to lysis of these cells greatly reduces the amount of insulin secreted. A current theory links type I diabetes to infection by the Coxsackievirus, a common cause of colds and enteric infections in a possible case of molecular mimicry.

Myasthenia gravis is named for the pronounced muscle weakness that is its principal symptom. Although the disease afflicts all skeletal muscle, the first effects are usually felt in the muscles of the eyes and throat. Eventually, it can progress to complete loss of muscle function and death. The classic syndrome is caused by autoantibodies binding to the receptors for acetylcholine, a chemical required to transmit a nerve impulse across the synaptic junction to a muscle (figure 1). The immune attack so severely damages the muscle cell membrane that transmission is blocked and paralysis ensues. Current treatment usually includes immunosuppressive drugs and therapy to remove the autoantibodies from the circulation. Experimental therapy using immunotoxins to destroy lymphocytes that produce autoantibodies shows some promise.

Fig. 1. Mechanism for involvement of autoantibodies in myasthenia gravis. Left: Normal process. Right: Antibodiesdeveloped against receptors on the postsynaptic membrane block themso that acetylcholine cannot bind and muscle contraction is inhibited.

Multiple sclerosis (MS) is a paralyzing neuromuscular disease associated with lesions in the insulating myelin sheath that surrounds neurons in the white matter of the central nervous system. The underlying pathology involves damage to the sheath by both T cells and autoantibodies; this damage severely compromises the capacity of neurons to send impulses. The principal motor and sensory symptoms are muscular weakness and tremors, difficulties in speech and vision, and some degree of paralysis. Most MS patients first experience symptoms as young adults, and they tend to experience remissions (periods of relief) alternating with recurrences of disease throughout their lives.

Convincing evidence from studies of the brain tissue of MS patients points to a strong connection between the disease and infection with viruses. Some research suggests that MS is associated with Epstein-Barr virus; newer evidence indicates that an endogenous retrovirus may be involved. The disease can be treated passively with monoclonal antibodies that target T cells, and a vaccine containing the myelin protein has shown beneficial effects. Immunosuppressants such as cortisone and interferon beta may also alleviate symptoms.

Дата добавления: 2015-06-04