Autoimmune polyendocrine syndrome type 1 and NALP5, a parathyroid autoantigen

Simple item page
dc.contributor.authorAlimohammadi, M.
dc.contributor.authorBjorklund, P.
dc.contributor.authorHallgren, A.
dc.contributor.authorPontynen, N.
dc.contributor.authorSzinnai, G.
dc.contributor.authorShikama, N.
dc.contributor.authorKeller, M.
dc.contributor.authorEkwall, O.
dc.contributor.authorKinkel, S.
dc.contributor.authorHusebye, E.
dc.contributor.authorGustafsson, J.
dc.contributor.authorRorsman, F.
dc.contributor.authorPeltonen, L.
dc.contributor.authorBetterle, C.
dc.contributor.authorPerheentupa, J.
dc.contributor.authorAkerstrom, G.
dc.contributor.authorWestin, G.
dc.contributor.authorScott, H.
dc.contributor.authorHollander, G.
dc.contributor.authorKampe, O.
dc.date.issued2008
dc.descriptionThe New England Journal of Medicine is owned, published, and copyrighted © 2008 Massachusetts Medical Society. All rights reserved
dc.description.abstractBackground 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.
dc.description.statementofresponsibilityMohammad Alimohammadi, Peyman Björklund, Åsa Hallgren, Nora Pöntynen, Gabor Szinnai, Noriko Shikama, Marcel P. Keller, Olov Ekwall, Sarah A. Kinkel, Eystein S. Husebye, Jan Gustafsson, Fredrik Rorsman, Leena Peltonen, Corrado Betterle, Jaakko Perheentupa, Göran Åkerström, Gunnar Westin, Hamish S. Scott, Georg A. Holländer,and Olle Kämpe
dc.identifier.citationNew England Journal of Medicine, 2008; 358(10):1018-1028
dc.identifier.doi10.1056/NEJMoa0706487
dc.identifier.issn0028-4793
dc.identifier.issn1533-4406
dc.identifier.orcidScott, H. [0000-0002-5813-631X]
dc.identifier.urihttp://hdl.handle.net/2440/53639
dc.language.isoen
dc.publisherMassachusetts Medical Soc
dc.source.urihttp://content.nejm.org/cgi/content/abstract/358/10/1018
dc.subjectParathyroid Glands
dc.subjectHumans
dc.subjectHypoparathyroidism
dc.subjectPolyendocrinopathies, Autoimmune
dc.subjectMitochondrial Proteins
dc.subjectNuclear Proteins
dc.subjectDNA, Complementary
dc.subjectRNA, Messenger
dc.subjectAutoantibodies
dc.subjectAutoantigens
dc.subjectGene Library
dc.subjectBiomarkers
dc.titleAutoimmune polyendocrine syndrome type 1 and NALP5, a parathyroid autoantigen
dc.typeJournal article
pubs.publication-statusPublished

Files

Collections

Medicine publications