title: Autoimmune polyendocrine syndrome type 1 and NALP5, a parathyroid autoantigen.
abstract: BACKGROUND
  Autoimmune polyendocrine syndrome type 1 (APS-1) is a multiorgan autoimmune disorder caused by mutations in AIRE, the autoimmune regulator gene. Though recent studies concerning AIRE deficiency have begun to elucidate the molecular pathogenesis of organ-specific autoimmunity in patients with APS-1, the autoantigen responsible for hypoparathyroidism, a hallmark of APS-1 and its most common autoimmune endocrinopathy, has not yet been identified.
  
  
  METHODS
  We performed immunoscreening of a human parathyroid complementary DNA library, using serum samples from patients with APS-1 and hypoparathyroidism, to identify patients with reactivity to the NACHT leucine-rich-repeat protein 5 (NALP5). Subsequently, serum samples from 87 patients with APS-1 and 293 controls, including patients with other autoimmune disorders, were used to determine the frequency and specificity of autoantibodies against NALP5. In addition, the expression of NALP5 was investigated in various tissues.
  
  
  RESULTS
  NALP5-specific autoantibodies were detected in 49% of the patients with APS-1 and hypoparathyroidism but were absent in all patients with APS-1 but without hypoparathyroidism, in all patients with other autoimmune endocrine disorders, and in all healthy controls. NALP5 was predominantly expressed in the cytoplasm of parathyroid chief cells.
  
  
  CONCLUSIONS
  NALP5 appears to be a tissue-specific autoantigen involved in hypoparathyroidism in patients with APS-1. Autoantibodies against NALP5 appear to be highly specific and may be diagnostic for this prominent component of APS-1.
authors.affiliation: University Hospital, Uppsala University, Uppsala, Sweden.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Alimohammadi
authors.forename: Peyman
authors.initials: P
authors.lastname: Björklund
authors.forename: Asa
authors.initials: A
authors.lastname: Hallgren
authors.forename: Nora
authors.initials: N
authors.lastname: Pöntynen
authors.forename: Gabor
authors.initials: G
authors.lastname: Szinnai
authors.forename: Noriko
authors.initials: N
authors.lastname: Shikama
authors.forename: Marcel P
authors.initials: MP
authors.lastname: Keller
authors.forename: Olov
authors.initials: O
authors.lastname: Ekwall
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Kinkel
authors.forename: Eystein S
authors.initials: ES
authors.lastname: Husebye
authors.forename: Jan
authors.initials: J
authors.lastname: Gustafsson
authors.forename: Fredrik
authors.initials: F
authors.lastname: Rorsman
authors.forename: Leena
authors.initials: L
authors.lastname: Peltonen
authors.forename: Corrado
authors.initials: C
authors.lastname: Betterle
authors.forename: Jaakko
authors.initials: J
authors.lastname: Perheentupa
authors.forename: Göran
authors.initials: G
authors.lastname: Akerström
authors.forename: Gunnar
authors.initials: G
authors.lastname: Westin
authors.forename: Hamish S
authors.initials: HS
authors.lastname: Scott
authors.forename: Georg A
authors.initials: GA
authors.lastname: Holländer
authors.forename: Olle
authors.initials: O
authors.lastname: Kämpe
mesh_terms: D001323:Autoantibodies / Q000032:analysis / Q000097:blood*; D001324:Autoantigens / Q000235:genetics / Q000276:immunology*; D015415:Biomarkers / Q000032:analysis / Q000097:blood; D018076:DNA, Complementary / Q000032:analysis; D015723:Gene Library; D006801:Humans; D007011:Hypoparathyroidism / Q000175:diagnosis* / Q000209:etiology / Q000276:immunology; D024101:Mitochondrial Proteins; D009687:Nuclear Proteins; D010280:Parathyroid Glands / Q000737:chemistry / Q000276:immunology*; D016884:Polyendocrinopathies, Autoimmune / Q000150:complications / Q000276:immunology*; D012333:RNA, Messenger / Q000032:analysis
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D015415:Biomarkers; D018076:DNA, Complementary; D024101:Mitochondrial Proteins; C527221:NLRP5 protein, human; D009687:Nuclear Proteins; D012333:RNA, Messenger