uu.seUppsala University Publications
Change search
ReferencesLink to record
Permanent link

Direct link
Autoimmune Polyendocrine Syndrome Type 1: NALP5 in Autoimmune Polyendocrine Syndrome Type 1
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
Show others and affiliations
2006 (English)In: The New England Journal of Medicine, Vol. 358, no 10, 1018-28 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2006. Vol. 358, no 10, 1018-28 p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-98038OAI: oai:DiVA.org:uu-98038DiVA: diva2:173202
Available from: 2009-02-11 Created: 2009-02-11 Last updated: 2009-09-29Bibliographically approved
In thesis
1. Molecular Targets in Autoimmune Polyendocrine Syndrome Type1 and Their Clinical Implications
Open this publication in new window or tab >>Molecular Targets in Autoimmune Polyendocrine Syndrome Type1 and Their Clinical Implications
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Autoimmune diseases occur when the immune system attacks and destroys healthy body tissue. Autoimmunity is known to cause a wide range of disorders, and is suspected to be responsible for many more. Most autoimmune disorders are chronic and cause severe morbidity for the patients, and are also costly for society. A majority of these disorders are today considered as complex diseases with incompletely known etiology. Hence, model systems for studying the pathogenesis of autoimmunity are important to unravel its causes.

Autoimmune Polyendocrine Syndrome Type 1 (APS-1), (OMIM 240300), is a rare autoimmune disorder. Patients with APS-1 progressively develop multiple organ-specific autoimmune lesions involving both endocrine and non endocrine tissues. Typical autoimmune disease components in APS-1 are hypoparathyroidism, Addison’s disease, vitiligo, alopecia and type 1 diabetes. The gene preventing APS-1 has been identified and designated Autoimmune Regulator (AIRE). It has been shown that mutations of AIRE cause loss of tolerance to self-structures, resulting in organ-specific autoimmunity.

Although APS-1 is a rare syndrome occurring mainly in genetically isolated populations, the disease components of APS-1 are, in isolated forms, not unusual in the general population and affect many patients. Hence, APS-1 is an attractive model disease for studies of molecular mechanisms underlying organ-specific autoimmunity.

This thesis concerns investigations in which two novel autoantigens are identified in APS-1 and used in serological diagnosis of the disease. NALP5, is identified as a parathyroid autoantigen - an important finding since autoimmune hypoparathyroidism is one of the cardinal symptoms of APS-1. Additionally, KCNRG is identified as a bronchial autoantigen in APS-1 patients with respiratory symptoms. Finally, studies that compare the immune response in APS-1 patients and the mouse model for APS-1 are presented.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2009. 59 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 417
autoimmunity, autoantibodies, endocrinology, parathyroid, hypoparathyroidism, Addison's disease, pulmonary symptoms, NALP, NALP5, NLR, KCNRG
National Category
Cell and Molecular Biology
urn:nbn:se:uu:diva-9549 (URN)978-91-554-7403-4 (ISBN)
Public defence
2009-03-05, Enghoffsalen, Enterence 50, Akademiska Sjukhuset, Uppsala University Hospital, SE75185, 09:15 (English)
Available from: 2009-02-11 Created: 2009-02-11 Last updated: 2009-04-17Bibliographically approved

Open Access in DiVA

No full text

Other links

By organisation
Department of Medical Sciences
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar

Total: 461 hits
ReferencesLink to record
Permanent link

Direct link