SIGNIFICANCE OF TISSUE-SPECIFIC AND TISSUE NON SPECIFIC AUTOIMMUNE REACTIONS OF GRAVES-DISEASE

The relationship between the many immunologic abnormalities demonstrat ed in the peripheral blood of patients with Graves' disease (GD) and t he broad spectrum of clinical features with which patients may present has not yet been addressed in detail. In this review we examine the e vidence to support the notion that GD could be considered a multi-syst em autoimmune disorder in which tissue damage is restricted to the thy roid gland connective tissue of the skin and orbit, extra-ocular and o ther skeletal muscles and possibly, the lacrimal glands.Apart from the well recognized reactions of autoantibodies and sensitized T lymphocy tes with epitopes on the thyroid specific TSH receptor, thyroid peroxi dase and thyroglobulin, in patients with hyperthyroidism, there is als o good evidence for autoantibody and, to a lesser extent, T lymphocyte reactivity with several eye muscle, other skeletal muscle and connect ive tissue, antigens in patients with ophthalmopathy, systemic myopath y, dermopathy and acropachy. There is also some evidence for immunorea ctivity against lacrimal gland antigens inpatients with ophthalmopathy associated with other features of GD. There are, in addition, a varie ty of organ non-specific reactions in GD; antinuclear antibodies are d etected in serum from about one-third of patients with hyperthyroidism and ophthalmopathy, while from 5% to 10% have antibodies reactive wit h several other ubiquitous tissue proteins. Cloned proteins which are autoantigenic in some patients with hyperthyroidism or Hashimoto's thy roiditis and ophthalmopathy include collagen XIII, nebulin, the calciu m binding protein calmitine, and the Mac-II antigen. All antibodies re active with eye muscle antigens, except the 64 kDa protein which is al so expressed in the thyroid cross react with the same, or a related pr otein in other skeletal muscle. Future research should focus on the un derlying mechanisms for this broad loss of tolerance to self antigens and the effect of environmental factors such as stress, radioiodine an d viral infection of the thyroid gland and other target tissues, in pr ecipitating disease.