Activating autoantibodies against the calcium-sensing receptor detected in two patients with autoimmune polyendocrine syndrome type 1

J Clin Endocrinol Metab. 2009 Dec;94(12):4749-56. doi: 10.1210/jc.2009-1080. Epub 2009 Oct 16.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Autoantibodies / immunology*
  • Cell Line
  • Child
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Female
  • Humans
  • Hypoparathyroidism / metabolism
  • Immunoglobulin G / biosynthesis
  • Immunoglobulin G / immunology
  • Inositol Phosphates / metabolism
  • Male
  • Middle Aged
  • Phosphorylation
  • Polyendocrinopathies, Autoimmune / immunology*
  • Receptors, Calcium-Sensing / immunology*


  • Autoantibodies
  • Immunoglobulin G
  • Inositol Phosphates
  • Receptors, Calcium-Sensing
  • Extracellular Signal-Regulated MAP Kinases