Kifor Olga, McElduff Aidan, LeBoff Meryl S, Moore Francis D, Butters Robert, Gao Ping, Cantor Thomas L, Kifor Imre, Brown Edward M
Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts 02115, USA.
J Clin Endocrinol Metab. 2004 Feb;89(2):548-56. doi: 10.1210/jc.2003-031054.
Autoimmune hypoparathyroidism is thought to result from immune-mediated destruction of the parathyroid glands. We encountered two patients with hypoparathyroidism and other autoimmune conditions (Graves' disease and Addison's disease, respectively) in whom autoimmune destruction of the parathyroid glands had not taken place. In the first, a histologically normal parathyroid gland was observed at the time of subtotal thyroidectomy; and in the second, the hypoparathyroidism remitted spontaneously. Both patients had antibodies that reacted with the cell surface of bovine parathyroid cells and human embryonic kidney (HEK293) cells transfected with the extracellular calcium-sensing receptor (CaR) but not with nontransfected HEK293 cells. The antibodies also reacted with the same bands on Western analysis of extracts of bovine parathyroid tissue and CaR-transfected HEK293 cells that were identified by an authentic, polyclonal, anti-CaR antiserum and reacted with several peptides with sequences from the CaR's extracellular domain. These anti-CaR antibodies activated the receptor based on their ability to increase inositol phosphate accumulation, activate MAPK, and inhibit PTH secretion. These results, therefore, demonstrate that patients with the biochemical findings of primary hypoparathyroidism can harbor activating antibodies to the CaR, which, in the two cases studied here, did not produce irreversible destruction of the parathyroid glands.
自身免疫性甲状旁腺功能减退症被认为是由免疫介导的甲状旁腺破坏所致。我们遇到了两名甲状旁腺功能减退症患者，他们分别伴有其他自身免疫性疾病（格雷夫斯病和艾迪生病），但甲状旁腺并未发生自身免疫性破坏。在第一例患者中，甲状腺次全切除术时观察到甲状旁腺组织学正常；在第二例患者中，甲状旁腺功能减退症自发缓解。两名患者体内均有抗体，这些抗体可与牛甲状旁腺细胞以及转染了细胞外钙敏感受体（CaR）的人胚肾（HEK293）细胞的细胞表面发生反应，但不与未转染的HEK293细胞发生反应。在对牛甲状旁腺组织提取物和转染了CaR的HEK293细胞进行蛋白质印迹分析时，这些抗体与经 authentic、多克隆抗CaR抗血清鉴定出的相同条带发生反应，并与来自CaR细胞外结构域序列的几种肽发生反应。基于其增加肌醇磷酸积累、激活丝裂原活化蛋白激酶（MAPK）以及抑制甲状旁腺激素（PTH）分泌的能力，这些抗CaR抗体激活了该受体。因此，这些结果表明，具有原发性甲状旁腺功能减退症生化表现的患者体内可能存在激活CaR的抗体，在此研究的两例病例中，这些抗体并未导致甲状旁腺的不可逆破坏。
