Genetic Susceptibility to Graves’ Ophthalmopathy
نویسندگان
چکیده
Graves’ disease (GD) is an autoimmune thyroid disorder (AITD) with aberrant antibody production resulting in hyperthyroidism [1]. It is characterized by T cell and B cell reactivity to the thyrotropin (thyroid stimulating hormone; TSH) receptor (TSHR) located on the endothelial surface of thyroid follicular cells, and the presence of abundant serum antibodies against TSHR (TRAb) is used as a specific marker of GD. Follicular hyperplasia, intracellular colloid droplets, cell thinning and patchy T cell-predominant lymphocytic infiltrations can be observed in thyroid gland histology of GD patients. GD is considered primarily a T helper-2 (Th2) autoimmune disease, as TRAb stimulates TSHR as an agonist, resulting in the excessive production of thyroid hormones. The pathogenesis of GD has been studied for decades and several risk factors have been identified. Similar to other autoimmune diseases, GD is believed to develop because of a combination of genetic susceptibility and environmental triggers. Often there is a familial history of disease and it is prevalent in women [2]. These facts support a role for genetic susceptibility in the pathogenesis of GD. Environmental factors are also considered important for the susceptibility and onset of disease. Infections have been predicted to have a pivotal role in triggering autoimmune reactions and the breakdown of tolerance leading to GD, although evidence is scarce. Patients with GD frequently have a history of some type of psychological and/or physiological stress [3]. Recently, epigenetic factors have also been demonstrated to be involved in autoimmune pathogenesis [4]. Classical GD was descri‐ bed as a syndrome consisting of tachycardia, goiter and orbitopathy, called “Merseburg triad”. Most GD patients develop tachycardia and goiter; however, GD patients with orbitopathy, named Graves’ ophthalmopathy (GO), occur in up to 60% of all GD patients [5]. In particular, GO worsens the patients quality of life because of its intractable symptoms, including diplopia, proptosis, chemosis and retro-orbital pain. With severe GO patients may risk visual loss. Moreover, GO is also experienced in patients with Hashimoto’s thyroiditis (HT) across ethnic backgrounds [6, 7]. HT is another common AITD, which is thought to develop from a combi‐
منابع مشابه
KIR Gene Content Does Not Contribute to Susceptibility to Graves’ Disease
Background: Killer cell immunoglobulin-like receptors (KIR) are expressed on NK cells and a subset of T cells. The variable KIR receptors along with their ligands, HLA class I, influence risk for autoimmune and malignant diseases. Objective: To investigate the KIR gene profiles in relation to susceptibility to Graves’ disease in patients with ophthalmopathy. Methods: KIR genes profiles were ana...
متن کاملAssociation of Human Leukocyte Antigens Class I & II with Graves’ Disease in Iranian Population
Background: Graves’ disease (GD), a highly rampant autoimmune disorder of the thyroid gland, is responsible for 60-80% of the clinical cases of hyperthyroidism. Over the past decades, genetic association studies have identified several GD susceptibility loci in CTLA-4, TSHR and major histocompatibility complex regions. The information on the association between the human leukocyte antigens (HLA...
متن کاملAuthor's response to reviews Title: Toll-Like Receptor Gene Polymorphisms are Associated with Susceptibility to Graves' Ophthalmopathy in Taiwan Males Authors:
متن کامل
Etiopathogenesis of Graves' disease.
Graves' disease is an autoimmune disorder, caused by thyroid-stimulating antibodies, which bind to and activate the thyrotropin receptor on thyroid cells, inducing the synthesis and release of thyroid hormones. It is a polygenic and multifactorial disease that develops as a result of complex interaction between genetic susceptibility and environmental and/or endogenous factors. Graves' disease ...
متن کاملAssociations of CTLA4 Gene Polymorphisms with Graves' Ophthalmopathy: A Meta-Analysis
Many studies have established that T-lymphocyte antigen-4 (CTLA4) is a susceptible gene for Graves' disease (GD). Also many studies showed the association between the CTLA4 exon-1 49A/G polymorphism and the risk of developing Graves' ophthalmopathy (GO) in GD patients. But those results were inconsistent. In recent years many new studies were published which helped to shed light on the relation...
متن کاملKIR gene content does not contribute to susceptibility to Graves' disease.
BACKGROUND Killer cell immunoglobulin-like receptors (KIR) are expressed on NK cells and a subset of T cells. The variable KIR receptors along with their ligands, HLA class I, influence risk for autoimmune and malignant diseases. OBJECTIVE To investigate the KIR gene profiles in relation to susceptibility to Graves' disease in patients with ophthalmopathy. METHODS KIR genes profiles were an...
متن کامل