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1.
J Clin Immunol ; 43(5): 979-988, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36867340

RESUMO

Immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is a serious disorder, which may comprise diabetes, thyroid disease, enteropathy, cytopenias, eczema, and other multi-system autoimmune dysfunction features. IPEX syndrome is caused by mutations in the forkhead box P3 (FOXP3) gene. Here, we report the clinical manifestations of a patient with IPEX syndrome onset in the neonatal period. A de novo mutation at exon 11 of the FOXP3 gene (c.1190G > A, p.R397Q) was found, and its main clinical manifestations included hyperglycemia and hypothyroidism. Subsequently, we comprehensively reviewed the clinical characteristics and FOXP3 mutations of 55 reported neonatal IPEX cases. The most frequent clinical presentation included symptoms of gastrointestinal involvement (n = 51, 92.7%), followed by skin-related symptoms (n = 37, 67.3%), diabetes mellitus (DM) (n = 33, 60.0%), elevated IgE (n = 28, 50.9%), hematological abnormality (n = 23, 41.8%), thyroid dysfunction (n = 18, 32.7%), and kidney-related symptoms (n = 13, 23.6%). In total, 38 variants were observed in the 55 neonatal patients. The most frequent mutation was c.1150G > A (n = 6; 10.9%), followed by c.1189C > T (n = 4; 7.3%), c.816 + 5G > A (n = 3; 5.5%), and C.1015C > G (n = 3; 5.5%), which were reported more than twice. The genotype-phenotype relationship showed that the repressor domain mutations were associated with DM (P = 0.020), and the leucine zipper mutations were associated with nephrotic syndrome (P = 0.020). The survival analysis suggested that treatment with glucocorticoids increased the survival of the neonatal patients. This literature review provides an informative reference for the diagnosis and treatment of IPEX syndrome in the neonatal period.


Assuntos
Hipotireoidismo Congênito , Diabetes Mellitus Tipo 1 , Doenças Genéticas Ligadas ao Cromossomo X , Doenças do Sistema Imunitário , Humanos , Hipotireoidismo Congênito/diagnóstico , Hipotireoidismo Congênito/genética , Diarreia , Doenças Genéticas Ligadas ao Cromossomo X/genética , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/genética , Doenças do Sistema Imunitário/genética , Mutação/genética , Fatores de Transcrição Forkhead/genética , Linfócitos T Reguladores
2.
Exp Lung Res ; 44(8-9): 424-432, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30755044

RESUMO

Bronchopulmonary dysplasia (BPD) is a common, chronic lung disease of infants. Presently, high oxygen exposure and mechanical ventilation considerably influence the development of BPD. To clarify the pathological mechanisms of this disease, we developed a hyperoxia-induced BPD rat model and investigated the role of CDKN1A in the pathogenesis of BPD. Newborn rats were randomly assigned to the hyperoxia (85% O2) and control (normoxia, 21% O2) groups. Lung tissues were collected on days 1, 3, 7, 14, or 21 after the start of hyperoxia or normoxia exposure. The expression of CDKN1A was detected by immunohistochemistry, western blot, and real-time PCR. Starting from day 3, CDKN1A mRNA expression was higher in the hyperoxia group. From day 7, the radial alveolar count was significantly different between the two groups, and on day 14, the hyperoxia group had high CDKN1A protein expression compared to the control group. These results suggest that increased CDKN1A expression may be involved in the pathogenesis of BPD through alveolarization and lung retardation.


Assuntos
Displasia Broncopulmonar/etiologia , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Hiperóxia , Lesão Pulmonar/etiologia , Animais , Animais Recém-Nascidos , Displasia Broncopulmonar/metabolismo , Inibidor de Quinase Dependente de Ciclina p21/análise , Modelos Animais de Doenças , Pulmão/química , Pulmão/metabolismo , Ratos , Fatores de Tempo
3.
Mol Med Rep ; 13(2): 1186-94, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26675943

RESUMO

Vitamin D and its receptor have a protective effect on epithelial barriers in various tissues. Low levels of vitamin D are associated with numerous pulmonary diseases, including acute lung injury (ALI) and acute respiratory distress syndrome. The present study investigated whether the vitamin D/vitamin D receptor (VDR) pathway may ameliorate lipopolysaccharide (LPS)­induced ALI through maintaining the integrity of the alveolar epithelial barrier. This was investigated by exposing wild­type (WT) and VDR knockout C57BL/6J mice to LPS, then comparing the healthy and LPS­treated mice lungs and bronchoalveolar lavage fluid (BALF). More specifically, lung histology, mRNA levels of proinflammatory cytokines and chemokines, and protein expression levels of tight junction proteins were determined. In addition, a vitamin D analog (paricalcitol) was administered to WT mice in order to investigate the effect of vitamin D on the alveolar epithelial barrier following exposure to LPS. VDR knockout mice exhibited severe lung injuries (P<0.001), increased alveolar permeability [demonstrated by a higher wet­dry ratio of lung weight (P<0.05), greater expression levels of BALF protein (P<0.001) and fluorescein isothiocyanate­conjugated 4 kDa dextran (P<0.001) leakage into the alveolar space], elevated proinflammatory cytokine and chemokine mRNA levels, as demonstrated by reverse transcription­quantitative polymerase chain reaction (P<0.05), and decreased protein and mRNA expression levels of occludin (P<0.01) and zonula occludens­1 (ZO­1; P<0.01) compared with WT mice. Paricalcitol treatment partially inhibited these pathological changes in WT mice by maintaining the mRNA and protein expression levels of occludin (P<0.01) and ZO­1 (P<0.05). A lack of VDRs in the pulmonary epithelial barrier appeared to compromise its defense, leading to more severe LPS­induced lung injury. Furthermore, vitamin D treatment alleviated LPS­induced lung injury and preserved alveolar barrier function. Therefore vitamin D treatment may present as a potential therapeutic strategy in ALI and acute respiratory distress syndrome.


Assuntos
Lesão Pulmonar Aguda/metabolismo , Lesão Pulmonar Aguda/patologia , Epitélio/patologia , Pulmão/patologia , Receptores de Calcitriol/metabolismo , Transdução de Sinais , Vitamina D/metabolismo , Animais , Quimiocinas/genética , Quimiocinas/metabolismo , Lipopolissacarídeos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Ocludina/metabolismo , Pneumonia/complicações , Pneumonia/patologia , Edema Pulmonar/complicações , Edema Pulmonar/patologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Junções Íntimas/metabolismo , Proteína da Zônula de Oclusão-1/metabolismo
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