CONTEXT: Autoimmune polyendocrine syndrome type 1 (APS1) is an autosomal recessive disorder caused by mutations in the autoimmune regulator (AIRE) gene. Hypoparathyroidism occurs in 80% of patients with APS1 and has been suggested to result from an autoimmune reaction against the calcium-sensing receptor (CaSR) in parathyroid cells. Anti-CaSR binding antibodies have previously been detected in patients with APS1. OBJECTIVE: The aim of this study was to determine whether anti-CaSR antibodies present in APS1 patients could modulate the response of the CaSR to stimulation by Ca(2+). RESULTS: The results indicated that two of the 14 APS1 patients included in the study had anti-CaSR antibodies that stimulated the receptor. These antibodies were detected by their ability to increase both Ca(2+)-dependent extracellular signal-regulated kinase phosphorylation and inositol phosphate accumulation in human embryonic kidney 293 cells expressing the CaSR. CONCLUSION: An important implication of the present results is that although the majority of APS1 patients do not have CaSR-stimulating antibodies, there may be a small but substantial minority of patients in whom the hypoparathyroid state is the result of functional suppression of the parathyroid glands rather than their irreversible destruction.
CONTEXT: Autoimmune polyendocrine syndrome type 1 (APS1) is an autosomal recessive disorder caused by mutations in the autoimmune regulator (AIRE) gene. Hypoparathyroidism occurs in 80% of patients with APS1 and has been suggested to result from an autoimmune reaction against the calcium-sensing receptor (CaSR) in parathyroid cells. Anti-CaSR binding antibodies have previously been detected in patients with APS1. OBJECTIVE: The aim of this study was to determine whether anti-CaSR antibodies present in APS1patients could modulate the response of the CaSR to stimulation by Ca(2+). RESULTS: The results indicated that two of the 14 APS1patients included in the study had anti-CaSR antibodies that stimulated the receptor. These antibodies were detected by their ability to increase both Ca(2+)-dependent extracellular signal-regulated kinase phosphorylation and inositol phosphate accumulation in humanembryonic kidney 293 cells expressing the CaSR. CONCLUSION: An important implication of the present results is that although the majority of APS1patients do not have CaSR-stimulating antibodies, there may be a small but substantial minority of patients in whom the hypoparathyroid state is the result of functional suppression of the parathyroid glands rather than their irreversible destruction.
Authors: K Nagamine; P Peterson; H S Scott; J Kudoh; S Minoshima; M Heino; K J Krohn; M D Lalioti; P E Mullis; S E Antonarakis; K Kawasaki; S Asakawa; F Ito; N Shimizu Journal: Nat Genet Date: 1997-12 Impact factor: 38.330
Authors: O Ekwall; H Hedstrand; L Grimelius; J Haavik; J Perheentupa; J Gustafsson; E Husebye; O Kämpe; F Rorsman Journal: Lancet Date: 1998-07-25 Impact factor: 79.321
Authors: John P Bilezikian; Aliya Khan; John T Potts; Maria Luisa Brandi; Bart L Clarke; Dolores Shoback; Harald Jüppner; Pierre D'Amour; John Fox; Lars Rejnmark; Leif Mosekilde; Mishaela R Rubin; David Dempster; Rachel Gafni; Michael T Collins; Jim Sliney; James Sanders Journal: J Bone Miner Res Date: 2011-10 Impact factor: 6.741
Authors: J Carl Pallais; E Helen Kemp; Clemens Bergwitz; Lakshmi Kantham; David M Slovik; Anthony P Weetman; Edward M Brown Journal: J Clin Endocrinol Metab Date: 2010-12-15 Impact factor: 5.958