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1.
Clin Immunol ; 197: 231-238, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30287219

RESUMO

Autoimmune polyendocrine syndrome type 1 (APS1) is characterized by multiorgan autoimmunity. We aim at characterizing a multi-center Brazilian cohort of APS1 patients by clinical evaluation, searching mutation in the AIRE gene, measuring serum autoantibodies, and investigating correlations between findings. We recruited patients based on the clinical criteria and tested them for AIRE mutations, antibodies against interferon type I and interleukins 17A, 17F and 22. We identified 12 unrelated families (13 patients) with typical signs of APS1 in the proband, and the screening of relatives recognized an asymptomatic child. Candidiasis was present in all cases, and 19 other manifestations were observed. All patients carried one of 10 different mutations in AIRE, being 3 new ones, and were positive for anti-interferon type I serum antibody. Anti-interleukin-17A levels inversely correlated with the number of manifestations in each patient. This negative correlation may suggest a protective effect of anti-interleukin-17A with a potential therapeutic application.


Assuntos
Autoanticorpos/imunologia , Citocinas/imunologia , Poliendocrinopatias Autoimunes/imunologia , Doença de Addison/etiologia , Adolescente , Adulto , Brasil , Candidíase Mucocutânea Crônica/etiologia , Criança , Estudos de Coortes , Consanguinidade , Análise Mutacional de DNA , Feminino , Humanos , Hipoparatireoidismo/etiologia , Interferon Tipo I/imunologia , Interferon alfa-2/imunologia , Interleucina-17/imunologia , Interleucinas/imunologia , Masculino , Mutação , Linhagem , Poliendocrinopatias Autoimunes/complicações , Poliendocrinopatias Autoimunes/genética , Poliendocrinopatias Autoimunes/fisiopatologia , Centros de Atenção Terciária , Fatores de Transcrição/genética , Adulto Jovem , Proteína AIRE , Interleucina 22
2.
Front Immunol ; 9: 567, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29666621

RESUMO

Autoimmune-polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a primary immunodeficiency caused by mutations in the autoimmune regulator gene (AIRE). Patients with AIRE mutations are susceptible to Candida albicans infection and present with autoimmune disorders. We previously demonstrated that cytoplasmic AIRE regulates the Syk-dependent Dectin-1 pathway. In this study, we further evaluated direct contact with fungal elements, synapse formation, and the response of macrophage-like THP-1 cells to C. albicans hyphae to determine the role of AIRE upon Dectin receptors function and signaling. We examined the fungal synapse (FS) formation in wild-type and AIRE-knockdown THP-1 cells differentiated to macrophages, as well as monocyte-derived macrophages from APECED patients. We evaluated Dectin-2 receptor signaling, phagocytosis, and cytokine secretion upon hyphal stimulation. AIRE co-localized with Dectin-2 and Syk at the FS upon hyphal stimulation of macrophage-like THP-1 cells. AIRE-knockdown macrophage-like THP-1 cells exhibited less Dectin-1 and Dectin-2 receptors accumulation, decreased signaling pathway activity at the FS, lower C. albicans phagocytosis, and less lysosome formation. Furthermore, IL-1ß, IL-6, or TNF-α secretion by AIRE-knockdown macrophage-like THP-1 cells and AIRE-deficient patient macrophages was decreased compared to control cells. Our results suggest that AIRE modulates the FS formation and hyphal recognition and help to orchestrate an effective immune response against C. albicans.


Assuntos
Candida albicans/imunologia , Hifas/imunologia , Macrófagos/imunologia , Fatores de Transcrição/imunologia , Candida albicans/fisiologia , Candidíase/genética , Candidíase/imunologia , Candidíase/microbiologia , Citocinas/imunologia , Citocinas/metabolismo , Células HEK293 , Humanos , Hifas/fisiologia , Lectinas Tipo C/genética , Lectinas Tipo C/imunologia , Lectinas Tipo C/metabolismo , Macrófagos/microbiologia , Mutação , Fagocitose/genética , Fagocitose/imunologia , Poliendocrinopatias Autoimunes/genética , Poliendocrinopatias Autoimunes/imunologia , Poliendocrinopatias Autoimunes/microbiologia , Interferência de RNA , Células THP-1 , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteína AIRE
3.
Arq Bras Endocrinol Metabol ; 56(1): 54-66, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22460196

RESUMO

Autoimmune 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.


Assuntos
Poliendocrinopatias Autoimunes , Adulto , Autoanticorpos/análise , Biomarcadores , Consanguinidade , Feminino , Humanos , Mutação/genética , Poliendocrinopatias Autoimunes/diagnóstico , Poliendocrinopatias Autoimunes/tratamento farmacológico , Poliendocrinopatias Autoimunes/genética , Poliendocrinopatias Autoimunes/imunologia , Fatores de Transcrição/genética , Fatores de Transcrição/imunologia , Proteína AIRE
4.
Arq. bras. endocrinol. metab ; 56(1): 54-66, fev. 2012. ilus, tab
Artigo em Inglês | LILACS | ID: lil-617917

RESUMO

Autoimmune 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.


Síndrome 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.


Assuntos
Adulto , Feminino , Humanos , Poliendocrinopatias Autoimunes , Autoanticorpos/análise , Biomarcadores , Consanguinidade , Mutação/genética , Poliendocrinopatias Autoimunes/diagnóstico , Poliendocrinopatias Autoimunes/tratamento farmacológico , Poliendocrinopatias Autoimunes/genética , Poliendocrinopatias Autoimunes/imunologia , Fatores de Transcrição/genética , Fatores de Transcrição/imunologia
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