Autoantibodies against Type I Interferons as an Additional Diagnostic Criterion for Autoimmune Polyendocrine Syndrome Type I

Meloni, Antonella; Furcas, Maria; Cetani, Filomena; Marcocci, Claudio; Falorni, Alberto; Perniola, Roberto; Pura, Mikuláš; Wolff, Anette S. B.; Husebye, Eystein S.; Lilić, Desa; Ryan, Kelli R.; Gennery, Andrew R.; Cant, Andrew J.; Abinun, Mario; Spickett, Gavin P; Arkwright, Peter D.; Denning, David W.; Costigan, Colm; Domínguez, María del Carmen; McConnell, Vivienne; Willcox, Nick; Meager, Anthony

doi:10.1210/jc.2008-0935

Cited by 176 publications

(126 citation statements)

References 42 publications

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“…48 More recently, an additional criterion has been proposed based on the presence of neutralizing autoantibodies against type I interferons and interleukin (IL)-17A, IL-17F and/ or IL-22 in nearly all APS-1 patients. 49,50 The disease usually manifests in childhood with chronic candidiasis; all three of the main clinical manifestations are present by age 20 in about a third of the patients. 51 However, the clinical course and phenotype of the disease vary widely and although there is some association with certain human leukocyte antigen class II haplotypes, the specific mutation in the AIRE gene does not seem to dictate clinical phenotype.…”

Section: Autoimmune Oophoritis As a Cause For Primary Ovarian Insuffimentioning

confidence: 99%

Ovarian autoimmune disease: clinical concepts and animal models

et al. 2014

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The ovary is not an immunologically privileged organ, but a breakdown in tolerogenic mechanisms for ovary-specific antigens has disastrous consequences on fertility in women, and this is replicated in murine models of autoimmune disease. Isolated ovarian autoimmune disease is rare in women, likely due to the severity of the disease and the inability to transmit genetic information conferring the ovarian disease across generations. Nonetheless, autoimmune oophoritis is often observed in association with other autoimmune diseases, particularly autoimmune adrenal disease, and takes a toll on both society and individual health. Studies in mice have revealed at least two mechanisms that protect the ovary from autoimmune attack. These mechanisms include control of autoreactive T cells by thymus-derived regulatory T cells, as well as a role for the autoimmune regulator (AIRE), a transcriptional regulator that induces expression of tissue-restricted antigens in medullary thymic epithelial cells during development of T cells. Although the latter mechanism is incompletely defined, it is well established that failure of either results in autoimmune-mediated targeting and depletion of ovarian follicles. In this review, we will address the clinical features and consequences of autoimmune-mediated ovarian infertility in women, as well as the possible mechanisms of disease as revealed by animal models.

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Section: Autoimmune Oophoritis As a Cause For Primary Ovarian Insuffimentioning

confidence: 99%

Ovarian autoimmune disease: clinical concepts and animal models

et al. 2014

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“…Besides the tissue-related self-Abs, it has been found that APS-1 patients virtually always develop high-titer neutralizing type I IFN-alpha and IFN-omega self-Abs (6,13). Type I IFNs are known to be antiviral and antiproliferative cytokines, and they also stimulate cytotoxic activity in a variety of cells of the immune system.…”

Section: Self-antibodiesmentioning

confidence: 99%

“…When relatives of a patient are analyzed, only one condition is required for APS-1 diagnosis (5). Recently, some authors have proposed that genetic studies and anti-interferon (IFN) antibodies (Abs) should be included as diagnostic criteria (6).…”

Section: Introductionmentioning

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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“…Although this diagnostic criterion is valid, it leaves many patients unrecognized. Recently, Meloni et al proposed the presence of autoantibodies against interferon -ω and α 2 to diagnose APECED in patients with just one of the APECED triad (7,8) . Due to its high sensitivity and specifi city this test has been proposed as a simpler diagnostic option than detecting AIRE mutations (8) .…”

Section: Discussionmentioning

confidence: 99%

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome (APECED) due to AIRET16M mutation in a consanguineous Greek girl

Kollios¹,

Tsolaki²,

Antachopoulos³

et al. 2011

Journal of Pediatric Endocrinology and Metabolism

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Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome (APECED) or autoimmune polyendocrine syndrome type 1 (APS-1) is a rare autosomal recessive disease caused by mutations of the AutoImmune REgulator ( AIRE ) gene, an important mediator of tolerance to self-antigens. It is characterized by two out of three major components: chronic mucocutaneous candidiasis, hypoparathyroidism and Addison ' s disease. We present an 11-yearold girl suffering from recurrent episodes of mucocutaneous candidiasis and onychomycosis from 1 to 6 years of age, and transient alopecia at the age of 4 years. Hypoparathyroidism and dental enamel hypoplasia were diagnosed at 8 years. Autoantibodies to thyroid and adrenal glands were not detected and all other endocrine functions have remained normal. Genetic analysis revealed that the patient was homozygous for the mutation T16M in exon 1 of the AIRE gene (p.T16M, c.47C > T). This is the fi rst APECED case reported for carrying this mutation in homozygous form. Parents were third cousins and heterozygous carriers of this mutation.

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Autoantibodies against Type I Interferons as an Additional Diagnostic Criterion for Autoimmune Polyendocrine Syndrome Type I

Abstract: Otherwise restricted to patients with thymoma and/or myasthenia gravis, these precocious persistent antibodies show 98% or higher sensitivity and APS-I specificity and are thus a simpler diagnostic option than detecting AIRE mutations.

Cited by 176 publications

References 42 publications

Ovarian autoimmune disease: clinical concepts and animal models

Ovarian autoimmune disease: clinical concepts and animal models

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

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome (APECED) due to AIRET16M mutation in a consanguineous Greek girl

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