Abstract Autoimmune thyroid disease (AITD) includes Graves’ disease (GD), chronic lymphoid thyroiditis, and idiopathic hypothyroidism, and is often associated with other autoimmune disorders. HLA-II and CTLA-4 genes play an important role in the development of GD and idiopathic hypothyroidism. The HLA-II and CTLA-4 genes play an important role in the development of GD and idiopathic hypothyroidism, and the TSH-R and IL-1ra genes are susceptibility genes for GD.AITD usually develops in response to environmental factors, such as fatigue, infections, trauma, stress, or increased iodine intake, and is characterized by lymphocytic infiltration of the thyroid gland and abnormally high levels of serum TRAb, TPOAb, and TGAb.AITD is the result of the interaction of genetic and environmental factors. AITD is the result of the interaction between genetic and environmental factors. Thyroid diseases are closely related to autoimmunity, and AITD includes Graves’ disease (GD), chronic lymphoid thyroiditis, and idiopathic hypothyroidism.AITD is often associated with other autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, systemic vasculitis, pernicious anemia, myasthenia gravis, vitiligo, and pemphigus vulgaris, among others. Autoimmunity is a phenomenon in which the body’s immune system mounts an immune response to its own components. The body’s immune response to foreign antigens usually results in the removal of the antigen, while the immune response to their own components of the immune response, their own cells or tissues are not easy to be completely removed by the immune system’s effector cells, but constantly attacked, as a result of which the body enters a state of disease, known as autoimmune disease. There are more than 80 autoimmune-related diseases, ranging from the life-threatening systemic lupus erythematosus (SLE) to autoimmune thyroid disorders, which have a relatively high incidence. Currently, research on autoimmunity focuses on the pathogenesis of autoimmune diseases. Possible mechanisms of AITD and autoimmune aspects are reviewed below. 1 Basic etiology of AITD Genetic factors The HLA-II and CTLA-4 genes play an important role in the pathogenesis of GD and idiopathic hypothyroidism, and the TSH-R and IL-1ra genes are also susceptibility genes for GD . Endogenous factors Women are more susceptible to AITD, which may be related to the effect of estrogen on the immune system. However, the reduced incidence of GD in pregnant women during pregnancy may again be related to the suppressed state of the immune system during pregnancy. Exogenous factors GD mostly develops due to external factors such as exertion, infection, trauma, stress or increased iodine intake as triggers. Infections can lead to an immune response in the thyroid gland by altering the autoantigens of the target organ or by cross-reactivity. Currently, the incidence of GD has increased due to increased iodine intake, which has been associated with increased thyroid lymphocyte infiltration, and has also increased the incidence of thyroiditis. 2 Immunologic Factors in Autoimmune Thyroid Disease Immunologic factors participating in AITD are humoral immunity, cellular immunity, immune complexes, cytokines, and Fas-mediated apoptosis, among others. Autoantigens of the thyroid gland The autoantigens of the thyroid gland are thyroglobulin (Tg), thyroid peroxidase (TPO) and thyroid-stimulating-hormone receptor (TSH-R). The presence of large numbers of antibodies against Tg, TPO, and TSH-R in patients with AITD suggests that humoral immunity plays a role in pathogenesis and that these antibodies play a very important role in the diagnosis of AITD. T cells The traditional theory is that autoantibodies are produced by B lymphocytes interacting with normal antigens due to decreased activity of suppressor T cells. In contrast, newer studies have suggested that sensitized T cells provide helper cytokines for autoantibody production. Cytokines IL-1α, IL-1β, IL-10, IFN-γ, IL-6, IL-8, and TNF-α have been found to be present in thyroid cells suffering from AITD.IL-1β inhibits TSH-stimulated thyroid function, and IL-1α/β inhibits gene expression of Tg and TPO.TNF-α inhibits thyroid follicular cell function in vitro, and it inhibits not only Tg and cAMP release, but also inhibits iodine uptake.IFN-γ induces thyroid cells to express HLA-class I molecules and HLA-class II molecules.IFN-γ also inhibits thyroid Tg, TPO, and TSH receptor expression, and results in decreased production of Tg, TPO, and iodine uptake.IFN-γ enhances the antigenicity of the thyroid on the one hand, and on the other hand, it inhibits differentiated cell function. In contrast to IFN-γ, TNF-α does not induce thyroid cells to express HLA-II-like molecules but inhibits the induction of IFN-γ. Autoantibodies and Immune Complexes Antithyroid antibodies are present in the serum of most AITD patients. Autoimmune disease effector antibodies are characterized by the following features: organ specificity; binding to specific cell surface antigens; and the ability to transfer autoimmune disease. Transfer of TSH-R antibodies (TSH-receptor angibody, TRAb) from patients with GD into normal subjects or into the fetus of a pregnant woman by passive transfer may induce hyperthyroidism. TRAb can be detected in 95% of patients with untreated GD and can cause hyperthyroidism. In other AITDs, thyroid autoantibodies act primarily as a pathogenetic mechanism and may be involved in the destruction of thyroid tissue.There are three types of antibodies in AITDs:1. Thyroid autoantibodies, in which the cellular components of the thyroid gland stimulate the immune system to produce antibodies, most of which are organ- and species-specific, to thyroid hormones.2. Thyroid antibodies are produced by the thyroid gland, which is composed of the antigens of thyroid gland components, follicular cells, and thyroid hormones. These antigens include thyroid gland components, thyroid follicular cells, and thyroid hormones.2 , Thyroid-stimulating antibodies, including thyroid-stimulating antibodies (TSAB) and thyroid stimulating hormone-binding inhibitory immunoglobulin (TBII).3 , Thyroid suppressor antibodies (TSBAb). Immune complexes (ICs) bind to thyroid cell membranes and modulate TSH receptors, and also have the effect of altering TSH receptors, which can be induced directly by binding to antibodies, by the complement pathway, or by the presence of multinucleated leukocytes. TGAb in anti-thyroid antibodies belongs to IgG, and thyroglobulin and antibody complexes can precipitate in the thyroid gland, activating K cells and destroying the thyroid gland. Antithyroid microparticle antibodies (TMAb) are now called antithyroid peroxidase antibodies (TPOAb) because their antigen is the enzyme thyroid peroxidase in the cytoplasm. TGAb and TPOAb are present in high titers in the sera of patients with chronic lymphocytic thyroiditis, but TPOAb levels are higher.TGAb is not as common in Graves’ disease as in chronic lymphocytic thyroiditis.TPOAb is present in more than 70% of patients with Graves’ disease, and a high titer of TPOAb may be useful in the diagnosis of chronic lymphocytic thyroiditis and may be useful in the diagnosis of Graves’ disease. Graves’ disease is informative. And high titer of TGAb suggests chronic lymphocytic thyroiditis. Fas and Fasl Apoptosis is a process of programmed necrosis of tissue cells, which not only plays a role in maintaining the physiological stability of normal tissues, but also plays an important role in the process of disease occurrence and development. Apoptosis also plays an important role in the autoimmune response. Apoptosis initiates cell necrosis through the binding of Fas and Fasl. Some studies have now found Fasl expression in thyroid cells. In chronic lymphocytic thyroiditis, apoptosis of the gland is increased, and a large number of lymphocytes infiltrate, destroying the follicular cells of the thyroid gland, and ultimately hypothyroidism is clinically present.3 Graves’ disease GD is a common disease, with a prevalence rate of 0.5%-1%, and a male-to-female ratio of 1:5-10.The HLA class II antigens are closely related to the pathogenesis of Graves’ disease, and environmental factors such as fatigue, a fast pace of life, stress, mental trauma, and so on, are often associated with its onset, Environmental factors such as fatigue, fast pace of life, stress, mental trauma, etc. are often triggered by GD. Stress can increase adrenocorticotropic hormone in the blood, which can alter the function of T-cells and enhance the immune response, thus aggravating the manifestation of GD, which are the triggering factors. Autoimmunity is usually considered to be the direct cause of GD.The pathogenesis of GD is as follows:1 Genetic factors, associated with abnormal expression of HLA, such as HLA-DR3.2 Decreased or defective function of suppressor T lymphocytes, which may be an imbalance between Th1 and Th2 cytokine polarization. Specific Th cells produce high levels of IFN-γ in the presence of monocytes and specific antigens.IFN-γ induces the expression of HLA-DR antigens on the surface of thyroid cells.3 Environmental factors such as stress, infections, trauma, fast pace of life, medications, and so on suppress the function of the body’s immune system, which then changes normal thyroid cells into antigens.4 In 95% of patients with GD TRAb is elevated in the serum. TRAb binds to the TSH receptor in the thyroid follicular cell membrane, stimulating the thyroid to proliferate and synthesize and secrete more thyroid hormones, leading to hyperthyroidism. TRAb has high value in diagnosing Graves’ disease and determining the prognosis of Graves’ disease. 4 Lymphocytic thyroiditis Lymphocytic thyroiditis, also called Hashimoto’s thyroiditis, is a typical autoimmune disease. Due to the abnormality of cellular immunity, some cytokines such as IFN-γ and IL-6 are involved, and corresponding antibodies are produced, which destroys the thyroid gland through the lysis of cells by autoantibodies, the direct killing of CLT, and ADCC, and ultimately leads to hypothyroidism. Chronic lymphocytic thyroiditis and Graves’ disease share a similar pathogenesis. In the serum of patients with chronic lymphocytic thyroiditis, TGAb titers are elevated in 80-90% of patients, while serum TPOAb is elevated in more than 90% of patients. Diagnosis of chronic lymphocytic thyroiditis with reference to TGAb and TPOAb levels is of high value.