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
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-1β, 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.
Trabecular bone score (TBS) is an indirect and noninvasive measure of bone quality. A low TBS indicates degraded bone microarchitecture, predicts osteoporotic fracture, and is partially independent of clinical risk factors and bone mineral density (BMD). There is substantial evidence supporting the use of TBS to assess vertebral, hip, and major osteoporotic fracture risk in postmenopausal women, as well as to assess hip and major osteoporotic fracture risk in men aged > 50 years. TBS complements BMD information and can be used to adjust the FRAX (Fracture Risk Assessment) score to improve risk stratification. While TBS should not be used to monitor antiresorptive therapy, it may be potentially useful for monitoring anabolic therapy. There is also a growing body of evidence indicating that TBS is particularly useful as an adjunct to BMD for fracture risk assessment in conditions associated with increased fracture risk, such as type-2 diabetes, chronic corticosteroid excess, and other conditions wherein BMD readings are often misleading. The interference of abdominal soft tissue thickness (STT) on TBS should also be considered when interpreting these findings because image noise can impact TBS evaluation. A new TBS software version based on an algorithm that accounts for STT rather than BMI seems to correct this technical limitation and is under development. In this paper, we review the current state of TBS, its technical aspects, and its evolving role in the assessment and management of several clinical conditions.
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