Molecular Targets in Autoimmune Polyendocrine Syndrome Type1 and Their Clinical Implications
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 costl...
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Uppsala universitet, Institutionen för medicinska vetenskaper
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ndltd-UPSALLA1-oai-DiVA.org-uu-95492013-01-08T13:05:04ZMolecular Targets in Autoimmune Polyendocrine Syndrome Type1 and Their Clinical ImplicationsengAlimohammadi, MohammadUppsala universitet, Institutionen för medicinska vetenskaperUppsala : Acta Universitatis Upsaliensis2009autoimmunityautoantibodiesendocrinologyparathyroidhypoparathyroidismAddison's diseasepulmonary symptomsNALPNALP5NLRKCNRGMolecular medicineMolekylär medicinAutoimmune 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. Doctoral thesis, comprehensive summaryinfo:eu-repo/semantics/doctoralThesistexthttp://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-9549urn:isbn:978-91-554-7403-4Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, 1651-6206 ; 417application/pdfinfo:eu-repo/semantics/openAccess |
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language |
English |
format |
Doctoral Thesis |
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autoimmunity autoantibodies endocrinology parathyroid hypoparathyroidism Addison's disease pulmonary symptoms NALP NALP5 NLR KCNRG Molecular medicine Molekylär medicin |
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autoimmunity autoantibodies endocrinology parathyroid hypoparathyroidism Addison's disease pulmonary symptoms NALP NALP5 NLR KCNRG Molecular medicine Molekylär medicin Alimohammadi, Mohammad Molecular Targets in Autoimmune Polyendocrine Syndrome Type1 and Their Clinical Implications |
description |
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. |
author |
Alimohammadi, Mohammad |
author_facet |
Alimohammadi, Mohammad |
author_sort |
Alimohammadi, Mohammad |
title |
Molecular Targets in Autoimmune Polyendocrine Syndrome Type1 and Their Clinical Implications |
title_short |
Molecular Targets in Autoimmune Polyendocrine Syndrome Type1 and Their Clinical Implications |
title_full |
Molecular Targets in Autoimmune Polyendocrine Syndrome Type1 and Their Clinical Implications |
title_fullStr |
Molecular Targets in Autoimmune Polyendocrine Syndrome Type1 and Their Clinical Implications |
title_full_unstemmed |
Molecular Targets in Autoimmune Polyendocrine Syndrome Type1 and Their Clinical Implications |
title_sort |
molecular targets in autoimmune polyendocrine syndrome type1 and their clinical implications |
publisher |
Uppsala universitet, Institutionen för medicinska vetenskaper |
publishDate |
2009 |
url |
http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-9549 http://nbn-resolving.de/urn:isbn:978-91-554-7403-4 |
work_keys_str_mv |
AT alimohammadimohammad moleculartargetsinautoimmunepolyendocrinesyndrometype1andtheirclinicalimplications |
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1716508518912098304 |