The Hypoparathyroidism of Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy Protective Effect of Male Sex

Gylling, M; Kääriäinen, Essi; Väisänen, Riitta; Kerosuo, Laura; Solin, Marja-Liisa; Halme, Leena; Saari, Seppo; Halonen, Maria; Kämpe, Olle; Perheentupa, Jaakko; Miettinen, Aaro

doi:10.1210/jc.2003-030700

Cited by 56 publications

(28 citation statements)

References 39 publications

(49 reference statements)

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“…In APS I, males are partially protected from the development of autoimmune hypoparathyroidism. 45 Also, gonadal insufficiency is recognized in 60% of the female patients 1 but is rarely seen among the male patients.…”

Section: Discussionmentioning

confidence: 99%

Aire-deficient mice develop hematopoetic irregularities and marginal zone B-cell lymphoma

Hässler

Ramsey

Karlsson

et al. 2006

Blood

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Autoimmune polyendocrine syndrome type I (APS I) is an inherited recessive disorder with a progressive immunological destruction of many tissues including the adrenal cortex, the parathyroid glands, and the gonads. APS I is caused by mutations in the AIRE gene (autoimmune regulator), expressed in cells of the thymus and spleen, suggesting a role in central and peripheral tolerance. Aire ؊/؊ mice replicate the autoimmune features of APS I patients with the presence of multiple autoantibodies and lymphocytic infiltrates in various tissues, but young mice appear clinically healthy. We here report the investigation of 15-to 24-monthold Aire ؊/؊ mice. We did not observe any endocrinological abnormalities, nor did sera from these mice recognize known APS I autoantigens. Interestingly, however, there was a high frequency of marginal zone B-cell lymphoma in Aire ؊/؊ mice and liver infiltrates of B cells, suggesting chronic antigen exposure and exaggerated activation. Furthermore, increased numbers of monocytes in blood were identified as well as augmented numbers of metallophilic macrophages in the spleen. We propose that Aire, in addition to its function in the thymus, also has a peripheral regulatory role by controlling the development of antigen-presenting cells ( IntroductionIn autoimmune polyendocrine syndrome type I 1 (APS I, or autoimmune-polyendocrinopathy-candidiasis-ectodermal dystrophy [APECED]; Online Mendelian Inheritance in Man [OMIM] no. 240300), an inherited autoimmune disorder without major histocompatibility complex (MHC) linkage, 2,3 patients progressively lose tolerance to various tissue-specific antigens, with ensuing endocrine and nonendocrine disorders. APS I patients suffer from multiple organ failures due to immunologic destruction of the adrenal cortex, the parathyroid glands, the liver, ␤-cells of the islets of Langerhans, and enterochromaffin cells of the small intestine. In addition, probably as a sign of immune dysfunction, the patients suffer from a chronic mucocutaneous candidiasis. 1 The prevalence of APS I is increased in Finland, Sardinia, and among Iranian Jews. [4][5][6] The disease-causing gene was localized to the long arm of chromosome 21 7 and has later been identified and named the autoimmune regulator (AIRE). 8,9 AIRE has been proposed to function as a transcription factor. [10][11][12][13][14] Aire is expressed in thymic medullary epithelial cells, in dendritic cells, [15][16][17][18] and in blood monocytes, 19 suggesting a role of Aire in both central and peripheral tolerance. To define the role of Aire in immunologic tolerance, we previously reported an Aire Ϫ/Ϫ mouse line engineered to reproduce the most common Finnish APS I mutation. 20 In analogy with APS I, Aire Ϫ/Ϫ mice display multiple organ-specific autoantibodies and lymphocytic infiltrates. 20,21 Since Aire is expressed in medullary epithelial cells of the thymus (mTEC), studies have so far focused on central tolerance and have addressed the role of Aire in negative selection. 21,22 Aire has been proposed to ac...

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Section: Discussionmentioning

confidence: 99%

Aire-deficient mice develop hematopoetic irregularities and marginal zone B-cell lymphoma

Hässler

Ramsey

Karlsson

et al. 2006

Blood

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“…Isolated primary HP is extremely rare, and therefore APECED diagnosis should be considered in any patient with this endocrinopathy. HP is the first endocrine disorder to develop in most APECED patients (e.g., in 64 % of Finnish patients) [7], but it can be diagnosed until 40 years of age [88]. Symptoms are related to hypocalcemia: muscle cramps, mild paresthesia and clumsiness [11].…”

Section: Endocrine Manifestationsmentioning

confidence: 99%

Autoimmune Polyendocrinopathy Candidiasis Ectodermal Dystrophy

Kisand

Peterson

2015

J Clin Immunol

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Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) is an autosomal recessive disease caused by mutations in the autoimmune regulator (AIRE) gene. This review focuses on the clinical and immunological features of APECED, summarizes the current knowledge on the function of AIRE and discusses the importance of autoantibodies in disease diagnosis and prognosis. Additionally, we review the outcome of recent immunomodulatory treatments in APECED patients.

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“…It varies according to gender, affecting 98% of female patients, but only 71% of male patients (17). Interestingly, when adrenal insufficiency is the first endocrinopathy, susceptibility to HP appears to be reduced (12,17).…”

Section: Clinical Manifestations Of Aps-1mentioning

confidence: 99%

Autoimmune polyendocrine syndrome type 1: case report and review of literature

Weiler

Silva

Lazaretti-Castro

2012

Arq Bras Endocrinol Metab

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SUMMARYAutoimmune polyendocrine syndrome type 1 (APECED) is a rare autosomal recessive disorder characterized by autoimmune multiorgan attack. The disease is caused by mutations in the autoimmune regulator gene (AIRE), resulting in defective AIRE protein, which is essential for selftolerance. Clinical manifestations are widely variable. Although the classic triad is composed by mucocutaneous candidiasis, hypoparathyroidism and adrenal failure, many other components may develop. Treatment is based on supplementation of the various deficiencies, and patients require regular follow-up throughout their lifespan. This article describes the case of a patient with the disease, and reviews literature data on the epidemiology, clinical course, immunogenetic aspects, diagnosis and treatment of the syndrome. Arq Bras Endocrinol Metab. 2012;56(1):54-66 SUMÁRIOSíndrome poliglandular autoimune tipo 1 é uma rara desordem autossômica recessiva caracterizada por ataque autoimune a diversos órgãos. A doença é causada por mutações no gene AIRE (autoimmune regulator), resultando em uma proteína AIRE defeituosa, proteína esta essencial para a manutenção da autotolerância. As manifestações clínicas são extremamente variáveis. A tríade clássica é composta por candidíase mucocutânea crônica, hipoparatiroidismo e insuficiência adrenal, porém diversos outros componentes podem estar presentes. A base do tratamento é a reposição das diversas deficiências, e os pacientes devem ser acompanhados por toda a vida. Este artigo descreve o caso de uma paciente com a síndrome e apresenta uma revisão sobre a epidemiologia, quadro clínico, aspectos imunogenéticos, diagnóstico e tratamento da desordem, de acordo com a literatura publicada. Arq Bras Endocrinol Metab. 2012;56(1):54-66

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The Hypoparathyroidism of Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy Protective Effect of Male Sex

Cited by 56 publications

References 39 publications

Aire-deficient mice develop hematopoetic irregularities and marginal zone B-cell lymphoma

Aire-deficient mice develop hematopoetic irregularities and marginal zone B-cell lymphoma

Autoimmune Polyendocrinopathy Candidiasis Ectodermal Dystrophy

Autoimmune polyendocrine syndrome type 1: case report and review of literature

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