PathwayType: signaling
PMID: 14654350
Pathway_Author: A. Nesterova ORCID:0000-0002-9448-8101
Organ: thyroid gland
Description: Graves disease (GD) is an autoimmune response to thyroid-specific antigens. Pathway is built manually using published studies.
Organ_System: endocrine system
Notes: Headnote: Graves disease (GD) is characterized by hyperthyroidism, particular ophthalmopathy, and pretibial myxedema. The disease is caused by an autoimmune response to thyroid antigens. As a result, the synthesis of thyroid hormones, metabolism, and the size of the thyroid increase. Signaling description: TSHR may act as an antigen that triggers the division and differentiation of lymphocytes and the production of antibodies. Occasionally, thyroid peroxidase (TPO) or thyroglobulin (TG) may also serve as antigens. Up to 90% of patients with GD have antibodies directed against TPO, while approximately 50% of patients have antibodies directed against TG. One of genetic causes for thyroid dysfunction may be single nucleotide polymorphisms (SNPs) in TSHR, MHC, CTLA4, and other genes. There are 3 main signaling pathways activated by TSHR including through G proteins-cAMP, G proteins-Ca2 activation, and STAT3 activation. Outcome effects: Activated by self-antigens, B cells produce immunoglobulins that enter the blood and bind to TSHR (in addition to TPO and TG). In GD patients, stimulatory, blocking, and neutral autoantibodies to TSHR present at the same time. Their degree of participation in GD progression varies significantly in different patients. When stimulatory antibodies prevail, the pathological effects on thyroid tissue are extensively produced. The TSHR signaling activation leads to the up-regulation of thyroid hormone synthesis and activation of thyroid cell proliferation. Highlighted proteins: Entities with increased expression or activity are highlighted in red and entities with decreased expression or activity are highlighted in blue.
NodeType: Pathway
Link: https://mammal-profservices.pathwaystudio.com/app/sd?urn=urn:agi-pathway:uuid-a301ea31-8d5c-4549-8d7c-b8581ed729c3
PMID: 20083159
Source: Diseases
PMID: 19258680
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