title: Prevalence and clinical associations of calcium-sensing receptor and NALP5 autoantibodies in Finnish APECED patients.
abstract: BACKGROUND
  Previous studies have identified the calcium-sensing receptor (CaSR) and NALP5 as parathyroid autoantibody targets in patients with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED). However, although NALP5 antibodies have been associated with the occurrence of hypoparathyroidism (HP) in APECED, it is unclear whether CaSR antibodies are a specific or sensitive marker for APECED-associated HP.
  
  
  OBJECTIVE
  The objective of the study was to identify associations between the presence of CaSR and NALP5 antibodies and the disease manifestations and demographic characteristics of Finnish APECED patients.
  
  
  METHODS
  This was a case-control study including 44 APECED patients and 38 age- and sex-matched healthy controls. Antibodies against the CaSR and NALP5 were detected using immunoprecipitation assays and radioligand binding assays, respectively.
  
  
  RESULTS
  CaSR and NALP5 antibodies were detected in 16 of 44 (36%) and 13 of 44 (30%) patients, respectively. No statistically significant associations were found between the presence of CaSR or NALP5 antibodies and the disease manifestations of APECED including HP (P > .05). For the diagnosis of HP, CaSR and NALP5 antibodies had specificities of 83% and 50%, respectively, and sensitivities of 39% and 26%, respectively. A significant association between both a shorter APECED and HP duration (<10 y) and positivity for CaSR antibodies was noted (P = .019 and P = .0061, respectively).
  
  
  CONCLUSIONS
  Neither CaSR nor NALP5 antibodies were found to be specific or sensitive markers for HP in APECED. Further investigations are required to determine the exact role of the autoimmune response against the CaSR and NALP5 in the pathogenesis of this autoimmune syndrome.
authors.affiliation: Department of Human Metabolism (E.H.K., M.H., H.K.S., A.P.W.), The Medical School, University of Sheffield, Sheffield S10 2RX, United Kingdom; Department of Dermatology, Allergology, and Venereology (N.K., A.R.), Institute of Clinical Medicine, University of Helsinki and Helsinki University Central Hospital, 00290 Helsinki, Finland; and Clinical Research Institute (K.J.E.K.), HUCH Ltd, 00029 HUS Helsinki, Finland.
authors.forename: E Helen
authors.initials: EH
authors.lastname: Kemp
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Habibullah
authors.forename: Nicolas
authors.initials: N
authors.lastname: Kluger
authors.forename: Annamari
authors.initials: A
authors.lastname: Ranki
authors.forename: Harpreet K
authors.initials: HK
authors.lastname: Sandhu
authors.forename: Kai J E
authors.initials: KJ
authors.lastname: Krohn
authors.forename: Anthony P
authors.initials: AP
authors.lastname: Weetman
mesh_terms: D000293:Adolescent; D000328:Adult; D001323:Autoantibodies / Q000097:blood*; D001324:Autoantigens / Q000276:immunology*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D005387:Finland / Q000453:epidemiology; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D024101:Mitochondrial Proteins; D009687:Nuclear Proteins; D016884:Polyendocrinopathies, Autoimmune / Q000097:blood / Q000453:epidemiology*; D044169:Receptors, Calcium-Sensing / Q000276:immunology*; D016036:Seroepidemiologic Studies; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D024101:Mitochondrial Proteins; C527221:NLRP5 protein, human; D009687:Nuclear Proteins; D044169:Receptors, Calcium-Sensing