| 摘要 |
Acquired hypoparathyroidism (AH) occurs frequently as a component of type I autoimmune polyglandular diseases (APS-I) or as a sporadic isolated disease in adults. Whereas autoantibodies to the parathyroid glands have been reported in AH, their very existence remains controversial. We report here the detection of autoantibodies as identified through immunoblotting using sera from AH patients. The antibodies were specific to parathyroid autoantigens obtained through differential centrifugation of fresh human hypercellular parathyroid glands, obtained shortly after their surgical removal for tertiary hyperparathyroidism in patients with renal failure. Autoantibodies were detected against several parathyroid specific proteins in the 17 AH sera tested. Twelve (70 %) reacted to a protein of 70 kDa, while 16 (94 %) reacted to a protein of 80 kDa, and 3 (18 %) reacted to a protein of 120-140 kDa, respectively. The 70 and 80 kDa proteins were localized to the cytosolic fraction of the parathyroid extract, and the 120-140 kDa protein to the membrane fraction. The autoantibodies were also detectable using a dog parathyroid gland as an antigen source. However, they could not be identified using cultured human melanocytes or in rat pituitary cells as antigen sources. Sera from 50 patients with various other autoimmune diseases as well as 22 normal controls were also tested, and none reacted with any of the above specific parathyroid proteins. It is concluded that autoantibodies to 3 major autoantigens in the human parathyroid gland extract have been detected in AH patients. Furthermore, our data indicates that the 120-140 kDa autoantigen is the calcium sensing receptor and that the reactive epitope largely resides in its extracellular domain. These data confirm the autoimmune nature of AH, and the invention provides a method for detecting AH or propensity for AH as well as a method for treating AH.
|
