title: AIRE gene mutations and autoantibodies to interferon omega in patients with chronic hypoparathyroidism without APECED.
abstract: OBJECTIVE
  To assess autoimmune regulator (AIRE) gene mutations, class II HLA haplotypes, and organ- or non-organ-specific autoantibodies in patients with chronic hypoparathyroidism (CH) without associated Addison's disease (AD) or chronic candidiasis (CC).
  
  
  METHODS
  Twenty-four patients who had CH without AD or CC were included in the study. AIRE gene mutations in all 14 exons were studied using PCR in 24 patients, 105 healthy controls and 15 first-degree relatives of CH patients with AIRE mutations. Human leucocyte antigens (HLA) were determined for all 24 patients and 105 healthy controls. Autoantibodies to a range of antigens including NACHT leucine-rich-repeat protein-5 (NALP5) and interferon omega (IFNω) were tested in all 24 patients.
  
  
  RESULTS
  AIRE gene mutations were found in 6 of 24 (25%) patients, all females, and this was significantly higher (P < 0·001) compared with AIRE mutations found in healthy controls (2/105). Three patients (12·5%) had homozygous AIRE mutations characteristic of Autoimmune-Poly-Endocrinopathy-Candidiasis-Ectodermal-Dystrophy and all three were also positive for IFNω-autoantibodies. Three patients (12·5%) had heterozygous AIRE mutations; two of these were novel mutations. One of the patients with heterozygous AIRE mutations was positive for both NACHT leucine-rich-repeat protein 5 and IFNω autoantibodies. Heterozygous AIRE mutations were found in 10 of 15 first-degree relatives of CH patients with AIRE mutations, although none was affected by CH. Class II HLA haplotypes were not statistically different in patients with CH compared to healthy controls.
  
  
  CONCLUSIONS
  Analysis of AIRE gene mutations together with serum autoantibody profile should be helpful in the assessment of patients with CH, in particular young women with associated autoimmune diseases.
authors: Department of Medical and Surgical Sciences Blood Transfusion Center, Azienda Ospedaliera-Università di Padova, Padova, Italy.
authors: Sara
authors: S
authors: Cervato
authors: Luca
authors: L
authors: Morlin
authors: Maria Paola
authors: MP
authors: Albergoni
authors: Stefano
authors: S
authors: Masiero
authors: Nella
authors: N
authors: Greggio
authors: Cristiano
authors: C
authors: Meossi
authors: Shu
authors: S
authors: Chen
authors: Maria
authors: M
authors: del Pilar Larosa
authors: Jadwiga
authors: J
authors: Furmaniak
authors: Bernard
authors: B
authors: Rees Smith
authors: Mohammad
authors: M
authors: Alimohammadi
authors: Olle
authors: O
authors: Kämpe
authors: Mariella
authors: M
authors: Valenzise
authors: Corrado
authors: C
authors: Betterle
mesh_terms: D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D005260:Female; D006680:HLA Antigens / Q000097:blood; D006801:Humans; D007011:Hypoparathyroidism / Q000235:genetics* / Q000276:immunology; D007370:Interferon Type I / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D016884:Polyendocrinopathies, Autoimmune / Q000235:genetics* / Q000276:immunology; D014157:Transcription Factors / Q000235:genetics*; D000096927:AIRE Protein
chemical_list: D001323:Autoantibodies; D006680:HLA Antigens; D007370:Interferon Type I; D014157:Transcription Factors; D000096927:AIRE Protein; C063743:interferon omega 1