A molecular hypothesis concerning the pathogenesis of myasthenia gravis

Abstract

The purine enzyme, adenosine deaminase, is essential for the maturation of lymphocytes, cell growth and normal immune function. Since adenosine deaminase has the highest activity in the thymus and in T lymphocytes, it is hypothesized that a defective or altered enzyme may be a cause of myasthenia gravis, a lymphoid dyscrasia. It is proposed that the alteration is on the non-catalytic portion of adenosine deaminase concerned with the normal immune function of T lymphocytes. Lymphocytes, particularly suppressor T lymphocytes containing a defective adenosine deaminase will function improperly. They will lose their normal immune regulatory function, allowing immunoglobulin-producing B lymphocytes to produce autoantibodies against the nicotinic acetylcholine receptor, with resultant induction and perpetuation of the autoimmune state. In an attempt to compensate for the defect, there may be hypertrophy of the thymus and lymphoid system, with overproduction of a defective adenosine deaminase. Since many of the functions of thymosin, the alleged active principle in thymus are identical to those of adenosine deaminase, it is postulated that thymosin may be a subunit of adenosine deaminase.