title: Calcium-sensing receptor autoantibodies and idiopathic hypoparathyroidism.
abstract: BACKGROUND
  Data on calcium-sensing receptor autoantibodies (CaSRAbs) in hypoparathyroidism are variable.
  
  
  OBJECTIVE
  We assessed the prevalence and significance of CaSRAbs in idiopathic hypoparathyroidism.
  
  
  METHODS
  This was a case-control study.
  
  
  METHODS
  One hundred forty-seven patients with idiopathic hypoparathyroidism treated during 1998-2011 in a tertiary care setting and 348 controls [healthy, n = 199; type 1 diabetes mellitus (T1DM), n = 99; and chronic lymphocytic thyroiditis (CLT), n = 50] participated in the study.
  
  
  METHODS
  CaSRAb assays included Western blot with CaSR protein expressed in Escherichia coli or human embryonic kidney (HEK)-293 cells, immunoprecipitation (IP) using in vitro-transcribed/translated protein, and indirect immunofluorescence on HEK293-CaSR. Functional significance was assessed by ERK1/2 phosphorylation. PTH and CaSR genes were sequenced for mutations.
  
  
  RESULTS
  E coli-Western blot assay revealed 16.3% CaSRAb positivity in idiopathic hypoparathyroidism, which was comparable with healthy subjects and CLT but significantly less than the T1DM controls. The prevalence of CaSRAbs on HEK293-Western blot (24.5%) against 150 kDa and/or 168 kDa protein in hypoparathyroidism was significantly higher than the healthy subjects, T1DM, and CLT. IP assay showed CaSRAbs in 12.9% of the hypoparathyroid patients but not in controls. The sensitivity and specificity of CaSRAbs in E coli and HEK-293-CaSR Western blot and IP assays were 16.3% and 83.1%, 24.5% and 88.9%, and 12.9% and 100%, respectively, and 42.1% of the cases detected were common in the IP assay and HEK293-Western blot. Duration of illness and coexistent autoimmunity were similar in patients with and without CaSRAbs. The CaSRAb-positive sera showed no immunofluorescence and phosphorylated ERK1/2 activity. The CaSR gene sequence was normal in all patients. One of the patients showed a novel p.Met1_Asp6del mutation in the signal peptide region of the PTH gene.
  
  
  CONCLUSIONS
  IP performed the best in detecting CaSRAbs in 12.9% of hypoparathyroid patients. Although CaSRAbs were functionally inert, its clinical relevance remains due to 100% specificity. Limited prevalence of CaSRAb suggests heterogeneity in the etiology of idiopathic hypoparathyroidism or the presence of CaSR epitopes other than those measured in the current study.
authors.affiliation: Department of Endocrinology and Metabolism, All India Institute of Medical Sciences, New Delhi 110029, India.
authors.forename: Neeraj
authors.initials: N
authors.lastname: Tomar
authors.forename: Nandita
authors.initials: N
authors.lastname: Gupta
authors.forename: Ravinder
authors.initials: R
authors.lastname: Goswami
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology; D016022:Case-Control Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000235:genetics / Q000276:immunology; D005260:Female; D057809:HEK293 Cells; D050031:Hashimoto Disease / Q000097:blood / Q000235:genetics / Q000276:immunology; D006801:Humans; D007011:Hypoparathyroidism / Q000097:blood / Q000235:genetics / Q000276:immunology*; D020935:MAP Kinase Signaling System / Q000502:physiology; D008297:Male; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000235:genetics / Q000276:immunology; D010766:Phosphorylation; D044169:Receptors, Calcium-Sensing / Q000235:genetics / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D010281:Parathyroid Hormone; D044169:Receptors, Calcium-Sensing