The human calcium-sensing receptor (CaSR) is a 1078 residue cell surface protein, which is predominantly expressed in the parathyroid glands and kidney. It is a member of the G protein-coupled receptor family. The CaSR allows regulation of parathyroid hormone (PTH) secretion and renal tubular calcium reabsorption in response to alterations in extracellular calcium concentrations. Abnormalities of the CaSR are associated with both hypercalcemic and hypocalcemic disorders.
The human CaSR gene is located on chromosome 3q21.1 and loss-of-function CaSR mutations have been reported in the hypercalcemic disoders of familial benign hypocalciric-hypercalcemia (FHH, FBH, or FBHH) and neonatal severe primary hyperparathyroidism (NSHPT).
CaSR autoantibodies have been found in FHH patients who did not have loss-of-function CaSR mutations, and in patients with an acquired form (i.e. autoimmune) of hypoparathyroidism. Autoimmune hypoparathyroidism can occur as an isolated clinical abnormality, as part of autoimmune polyendocrinopathy syndrome (APS-2 and APS-2). APS-1 most commonly comprises mucocutaneous candidiasis, hypoparathyroidism, and Addison's disease. APS-2 includes two or more of the following: Addison's disease, Graves' disease, autoimmune thyroiditis, type 1 diabetes mellitus, primary hypogonadism, myasthenia gravis, celiac sprue.
Studies have demonstrated that CaSR autoantibody is present in about one third of patients with isolated acquired hypoparathyroidism. On the other hand, it is also reported that some clinical primary hypoparathyroidism can harbor autoantibodies to human CaSR. Therefore, there is a great clinical value of detecting this autoantibody to assess the autoimmune origin of the disease.