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Previous Volume 358:1018-1028 March 6, 2008 Number 10 Next

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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.

Source Information

From University Hospital, Uppsala University, Uppsala, Sweden (M.A., P.B., Å.H., O.E., J.G., F.R., G.Å., G.W., O.K.); University of Helsinki and the National Public Health Institute, Biomedicum Helsinki (N.P., L.P.), and the Hospital for Children and Adolescents, Helsinki University Hospital (J.P.) — both in Helsinki; Laboratory of Pediatric Immunology, University of Basel, and the University Children's Hospital — both in Basel, Switzerland (G.S., N.S., M.P.K., G.A.H.); the Walter and Eliza Hall Institute of Medical Research and the University of Melbourne — both in Parkville, Victoria, Australia (S.A.K., H.S.S.); the Institute of Medicine, University of Bergen, and Haukeland University Hospital — both in Bergen, Norway (E.S.H.); and the University of Padua, Padua, Italy (C.B.).

Address reprint requests to Dr. Kämpe at the Department of Medical Sciences, Uppsala University Hospital, SE 75185, Uppsala, Sweden, or at olle.kampe{at}medsci.uu.se.

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