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A Benchmark for Autoimmunity

 
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Myasthenia gravis (MG) has been called a benchmark for understanding autoimmunity because the mechanism of illness is the simplest of all autoimmune conditions. The immune attack targets specific proteins in the neuromuscular junction. A wide variety of treatments have been used with some success. The goal of MG research is to correct the abnormality without interfering with other functions of the immune system.

The symptoms of myasthenia gravis include muscle weakness that worsens with use of the affected muscles, and often hits the eyelids first. These were described as early as 1664 in colonial America. In the 1800's, the condition was treated with surgery to remove the thymus and with anticholinesterase drugs including physostigmine from the Calabar bean. The treatments used today represent a spectrum of approaches which are used for most autoimmune conditions:

Corticosteroids. Steroids such as prednisone are used for a wide variety of inflammatory and autoimmune conditions. These drugs have multiple effects to reduce the number and function of lymphocytes in the affected areas.

Azathioprine. This is one of the oldest immunosuppressive drugs. It interferes with nucleic acid synthesis, thereby limiting T and B cell proliferation.

Cyclosporine. This drug is a cyclic peptide best known for suppressing the immune system's rejection of organ transplants. It interferes with the production of IL-2 by helper T cells.

Tacrolimus (Prograf) and mycophenolate mofetil (CellCept). These are newer drugs similar to cyclosporine that are also used for organ transplants.

Etanercept (Enbrel). This biologic drug blocks the action of tumor necrosis factor (TNF). See Ref. 2.

Plasmapheresis (plasma exchange). This process is similar to dialysis. Blood is removed from the patient and separated into cells and plasma. The plasma is replaced with a solution that contains small molecules normally found in the blood, but without the antibodies involved in immune response. The blood cells and solution are returned to the patient. See Ref. 3.

Immunoadsorption. Similar to plasmapheresis, this is a more specific technique for removing the antibodies that are causing the problem.

Thymectomy. The thymus gland is part of the immune system, located in the chest. Removal of this gland is still recommended for some myasthenia gravis patients. See Ref. 4.

Intravenous immunoglobulin, IVIg. This is a very specific transfusion of immunoglobulin proteins from human blood donors. The mechanism of action is complex.

Based on the results of these various approaches, research is in progress to develop new therapies to target the cause of autoimmune conditions more precisely.

References:

1. Conti-Fine BM et al, “Myasthenia gravis: past, present, and future”, Journal of Clinical Investigation 2006 Nov;116(11):2843-52.

2. TNF blockers:
https://www.empowher.com/news/herarticle/2009/12/17/tnf-blockers-miracle-drugs-or-minefields

3. Muscular Dystrophy Association information on plasmapheresis:
http://www.mda.org/publications/fa-plasmaph.html

4. Thymectomy:
http://www.netwellness.org/healthtopics/gravis/box5.cfm

Linda Fugate is a scientist and writer in Austin, Texas. She has a Ph.D. in Physics and an M.S. in Macromolecular Science and Engineering. Her background includes academic and industrial research in materials science. She currently writes song lyrics and health articles.

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