Genomic coordinate 10:39,800,001 & Cytoband 10q (AITD4).
Here I present: “Graves Disease Autoantigen”, Victor McKusick, Mendelian Inheritance in Man’, 1966. (AITD4) icd10=E05.90
In Graves’ Disease,is the thyrotropin receptor (TSHR)—also known as the TSH receptor—is the primary autoantigen.
The immune system incorrectly identifies this receptor as a threat, producing TSHR autoantibodies (TRAb) that mimic the action of thyroid-stimulating hormone (TSH). These antibodies bind to the receptor and continuously activate the thyroid gland, leading to the overproduction of thyroid hormones (hyperthyroidism) and the development of a goiter.
Key Characteristics of the TSHR Autoantigen.
Structure: TSHR is a G-protein coupled receptor primarily located on the surface of thyroid follicular cells.
The A-Subunit: The receptor undergoes intramolecular cleavage, shedding its extracellular A-subunit into circulation. This shed portion is considered the most immunogenic part of the receptor and is believed to initiate or amplify the autoimmune response.
Extrathyroidal Expression: TSHR is also expressed in other tissues, including adipocytes (fat cells) and orbital fibroblasts behind the eyes. This explains why the immune attack can also affect the eyes (Graves’ orbitopathy) and skin (pretibial myxedema).
Related Secondary Antigens
While TSHR is the hallmark antigen of Graves’ Disease, other autoantibodies are frequently found in patients, though they are more commonly associated with Hashimoto’s thyroiditis:
Thyroid Peroxidase (TPO): An enzyme involved in thyroid hormone synthesis.Thyroglobulin (Tg): A protein used by the thyroid gland to produce hormones.
IGF-1 Receptor: Recent research suggests antibodies to the insulin-like growth factor-1 (IGF-1) receptor may work alongside TRAb, particularly in the development of Thyroid-Eye Disease.
SUMMARY.
The genomic coordinate 10:39,800,001 corresponds to the AITD4 susceptibility locus on cytoband 10q. Autoimmune Thyroid Disease-4 (AITD4)is a susceptibility locus for Graves disease and Hashimoto thyroiditis.
