Study Of The Immune Pathogenesis In Patients With Graves'disease

Graves?disease(GD) refers to common form of hyperthyroidism which accounts for 80% of hyperthyroid patients. Besides diffuse enlargement of the gland, most of patients have infiltrating exophthalmos, myxedema and toxic symptoms. Although the exact causes of GD are unknow, studies indicated that autoimmune process may play an important role on pathogenesis, which is postulated that there is genetic predisposition under certain environmental factors, such as stressful life, and manifested as a organ specific autoimmune disease. At present, the disease is considered to be caused by antuantibodies, mainly IgG, directly against the thyrotropin receptor and activate the receptor, causing the autonomous production of thyroid hormones. Concerning about specific autoantigens, experiments demonstrated that most autoantibodies were against the thyroglobulin, thyroid peroxidase and TSH receptor which existed in thyroid tissues, thyroid stimulating Abs(TSAb) or thyroid stimulating immunoglobulin(TSI) were the main autoantibodies found. There is evidence for T cells involved in the development of GD. However, it is 7 ABSTRACT unclear whether this is inciting event or represents epiphenomenon secondary to the abnormal immune response. That is, T-suppressor cells appear to be functionally abnormal, and abnormal T-helper cells could stimulate B lymphocyte to produce autoantibodies, which act directly on the thyroid epithelial cells and lead to hyperfunction. Occasional evidence indicates that autoimmune process may be induced by changed autoantigens which caused by infection, radiation and damage. In clinic, currently available treatments for GD have remained limited to antithyroid drugs, radioiodine and surgery. But the long remission rate decreases with aging. It is generally accepted that normal immune response to foreign antigens depends on coordinating interaction between T cells and antigen-presenting cells(APCs). Activation of naive I lymphocytes requires two discrete signals. In the absence of second, or costimulatory signal, the T cell will lead to unresponsiveness(anergy). If second signal overstimuiate, it may activate autoreactive T lymphocyte and result in autoimmune response. Interactions between costimulatories and their Iigands are associated with the regulation of humoral immunity and cellular immunity. Recent experiments in vivo or in vitro have shown that several costimulatory molecules preferential effect at different stages of I cell activation/differentiation or promote the development of different effector functions. B7-CD28/CTLA-4 and CD4OICD4OL are two primary co-stimulatory molecules. Recently, It 8 ABSTRACT has been reported that increased expression of CD4O in GD thyroid epithelial cells, fibroblast cells and follicular cells was present. Cytokine is a kind of protein or polypeptide produced or secreted by immune cells. It exerts different biological effects through binding to its specific receptor on target cell. It is a biological response modifier involving in numerous immune response. Recent studies have confirmed that cytokine may play an important role in the pathogenesis of GD. For all these reasons, it...