title: Prevalence of calcium sensing receptor autoantibodies in patients with sporadic idiopathic hypoparathyroidism.
abstract: OBJECTIVE
  The pathogenesis of sporadic idiopathic hypoparathyroidism is unclear. The calcium sensing receptor (CaSR) plays a pivotal role in extracellular calcium homeostasis and is the candidate autoantigen in hypoparathyroidism associated with autoimmune polyglandular endocrinopathy syndrome. We therefore looked for antibodies (Ab) against the CaSR in patients with sporadic idiopathic hypoparathyroidism and their association, if any, with the major histocompatibility complex (MHC) class II human leukocyte antigen (HLA)-DR haplotypes.
  
  
  METHODS
  The subjects included 51 patients with sporadic idiopathic hypoparathyroidism and 45 healthy controls. Investigations included computerised tomography, serum calcium, phosphorus, thyroxine, TSH, cortisol, intact parathyroid hormone (iPTH), ACTH and thyroid peroxidase (TPO) and adrenal antibodies. The CaSRAb were assayed in patients' sera by Western blot. Genotyping of the HLA-DR locus was performed using PCR and sequence-specific oligonucleotide probes.
  
  
  RESULTS
  Intracranial calcification and cataract were present in 76.5% and 41.1% of the patients respectively and 62.7% had convulsions. Autoantibodies against the 168 kDa CaSR protein were demonstrated in the serum of 49.0% of the patients and in 13.3% of the controls (P<0.001). Pre-incubating serum samples from the CaSRAb-positive patients with parathyroid membrane produced a 90% decrease in the band intensity. HLA-DRB1*01 and DRB1*09 alleles were significantly associated with idiopathic hypoparathyroidism (relative risk of 7.8, P=0.001). The frequency of HLA-DRB1*09 and DRB1*10 alleles tended to be higher in patients positive for the CaSRAb. There was no significant difference in the frequency of occurrence of convulsions, cataract, intracranial calcification, calcium:phosphorus ratio, and iPTH levels between patients with and without CaSRAb.
  
  
  CONCLUSIONS
  49.0% of the patients studied had serological evidence of organ-specific autoimmunity against the CaSR protein. The occurrence of CaSRAb and the HLA-DR associations imply an autoimmune component to the disease, but the primary role of the CaSRAb in the pathogenesis of the disease needs to be assessed further.
authors.affiliation: Department of Endocrinology and Metabolism, All India Institute of Medical Sciences, New Delhi 110029, India. gosravinder@hotmail.com
authors.forename: Ravinder
authors.initials: R
authors.lastname: Goswami
authors.forename: Edward M
authors.initials: EM
authors.lastname: Brown
authors.forename: Narayana
authors.initials: N
authors.lastname: Kochupillai
authors.forename: Nandita
authors.initials: N
authors.lastname: Gupta
authors.forename: Rajni
authors.initials: R
authors.lastname: Rani
authors.forename: Olga
authors.initials: O
authors.lastname: Kifor
authors.forename: Naibedya
authors.initials: N
authors.lastname: Chattopadhyay
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D001323:Autoantibodies / Q000097:blood*; D005260:Female; D006684:HLA-DR Antigens / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D007011:Hypoparathyroidism / Q000453:epidemiology* / Q000276:immunology*; D008099:Liver / Q000276:immunology; D008297:Male; D009206:Myocardium / Q000276:immunology; D051381:Rats; D044169:Receptors, Calcium-Sensing / Q000276:immunology*; D016036:Seroepidemiologic Studies
chemical_list: D001323:Autoantibodies; D006684:HLA-DR Antigens; D044169:Receptors, Calcium-Sensing