title: Activating autoantibodies against the calcium-sensing receptor detected in two patients with autoimmune polyendocrine syndrome type 1.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Human Metabolism, School of Medicine, University of Sheffield, Royal Hallamshire Hospital, Glossop Road, Sheffield S10 2JF, United Kingdom. e.h.kemp@sheffield.ac.uk
authors.forename: E Helen
authors.initials: EH
authors.lastname: Kemp
authors.forename: Nikos G
authors.initials: NG
authors.lastname: Gavalas
authors.forename: Kai J E
authors.initials: KJ
authors.lastname: Krohn
authors.forename: Edward M
authors.initials: EM
authors.lastname: Brown
authors.forename: Philip F
authors.initials: PF
authors.lastname: Watson
authors.forename: Anthony P
authors.initials: AP
authors.lastname: Weetman
mesh_terms: D000293:Adolescent; D000328:Adult; D001323:Autoantibodies / Q000276:immunology*; D002460:Cell Line; D002648:Child; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D006801:Humans; D007011:Hypoparathyroidism / Q000378:metabolism; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000276:immunology; D007295:Inositol Phosphates / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D016884:Polyendocrinopathies, Autoimmune / Q000276:immunology*; D044169:Receptors, Calcium-Sensing / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D007074:Immunoglobulin G; D007295:Inositol Phosphates; D044169:Receptors, Calcium-Sensing; D048049:Extracellular Signal-Regulated MAP Kinases