RESUMO
AIM: Previous studies have suggested that Down's syndrome is an independent risk factor for severe respiratory infection due to respiratory syncytial virus (RSV). We compared the clinical characteristics of children with and without Down's syndrome hospitalised due to RSV. METHODS: This retrospective cohort study compared data from hospitalisations due to RSV lower respiratory tract infections (LRTI) in children under 14 years of age with (n = 58) and without (n = 58) Down's syndrome. RESULTS: The Down's group had longer hospital stays than the controls of six versus four days (p < 0.0001), even after adjusting for age, weeks of gestation at birth, presence of asthma, bronchopulmonary dysplasia, haemodynamically significant and nonsignificant congenital heart disease. This difference increased when only children under one year of age were analysed to 11 versus five days (p < 0.0001). Children with Down's syndrome were more likely to be admitted to intensive care unit (43.1% versus 22.4%, p = 0.017), need noninvasive mechanical ventilation (36.2% versus 13.7%, p = 0.005) and be prescribed antibiotics and steroids. CONCLUSION: Children with Down's syndrome hospitalised due to RSV LRTI had longer hospital stays and worse clinical courses than controls, highlighting the need for RSV prophylaxis for children with Down's syndrome, especially under one year of age.
Assuntos
Síndrome de Down/complicações , Pacientes Internados/estatística & dados numéricos , Infecções por Vírus Respiratório Sincicial/mortalidade , Criança , Pré-Escolar , Chile/epidemiologia , Comorbidade , Síndrome de Down/epidemiologia , Síndrome de Down/imunologia , Feminino , Mortalidade Hospitalar , Humanos , Lactente , Unidades de Terapia Intensiva Pediátrica/estatística & dados numéricos , Tempo de Internação/estatística & dados numéricos , Masculino , Respiração Artificial/estatística & dados numéricos , Infecções por Vírus Respiratório Sincicial/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de DoençaRESUMO
OBJECTIVE: The aim of the study was to investigate the expression patterns of a specific set of genes involved in the inflammation process in children with Down Syndrome (DS) and children without the syndrome (control group) to identify differences that may be related to the immune abnormalities observed in DS individuals. METHOD: RNA samples were obtained from peripheral blood, and gene expression was quantified using the TaqMan® Array Plate Human Inflammation Kit, which facilitated the investigation into 92 inflammation-related genes and four reference genes using real-time polymerase chain reaction (qPCR). RESULTS: Twenty genes showed differential expression in children with DS; 12 were overexpressed (PLA2G2D, CACNA1D, ALOX12, VCAM1, ICAM1, PLCD1, ADRB1, HTR3A, PDE4C, CASP1, PLA2G5, and PLCB4), and eight were underexpressed (LTA4H, BDKRB1, ADRB2, CD40LG, ITGAM, TNFRSF1B, ITGB1, and TBXAS1). After statistically correcting for the false discovery rate, only the genes BDKRB1 and LTA4H showed differential expression, and both were underexpressed within the DS group. CONCLUSION: DS children showed differential expression of inflammation-related genes that were not located on chromosome 21 compared with children without DS. The BDKRB1 and LTA4H genes may differentiate the case and control groups based on the inflammatory response, which plays an important role in DS pathogenesis.
Assuntos
Síndrome de Down/genética , Inflamação/genética , Proteínas Adaptadoras de Transdução de Sinal , Antígeno CD11b/genética , Canais de Cálcio Tipo L/genética , Caspase 1/genética , Criança , Pré-Escolar , Nucleotídeo Cíclico Fosfodiesterase do Tipo 4/genética , Síndrome de Down/imunologia , Feminino , Perfilação da Expressão Gênica , Fosfolipases A2 do Grupo II/genética , Fosfolipases A2 do Grupo V/genética , Humanos , Inflamação/imunologia , Molécula 1 de Adesão Intercelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Masculino , Proteínas de Membrana/genética , Fosfolipase C beta/genética , Fosfolipase C delta/genética , Reação em Cadeia da Polimerase em Tempo Real , Receptores Adrenérgicos beta 1/genética , Receptores Adrenérgicos beta 2/genética , Receptores 5-HT3 de Serotonina/genética , Receptores Tipo II do Fator de Necrose Tumoral/genética , Proteínas Recombinantes de Fusão/genética , Molécula 1 de Adesão de Célula Vascular/genéticaRESUMO
In addition to previously studied immunological variables, the relative expression of IFNGR2, IFNAR1, CD18, and CD275 (all encoded in chromosome 21) on circulating leucocytes and multifunctional T cells (evaluated by an intracellular cytokine/proliferation assay) were compared between children with Down syndrome (DS) and healthy controls (HC). As previously reported, numbers of lymphocytes, CD4(+) T cells, Treg cells, B cells, and levels of serum IgM were decreased, and levels of IgG and IgA were increased in children with DS. Moreover, the relative expression of CD18 on T and B cells (previously and not previously reported, respectively) were elevated in DS children (p⩽0.01). Age and numbers of B and Treg cells moderately correlated with retrospectively identified infection related hospitalizations (rho: 0.300-0.460, p⩽0.003). Age and the numbers of Treg cells also correlated with prospectively identified infection related hospitalizations. Future studies are necessary to clarify the role of these parameters in the immunity of DS patients.
Assuntos
Linfócitos B/imunologia , Cromossomos Humanos Par 21/genética , Síndrome de Down/imunologia , Hospitalização/estatística & dados numéricos , Infecções/imunologia , Subpopulações de Linfócitos T/imunologia , Linfócitos T Reguladores/imunologia , Adolescente , Antígenos CD18/metabolismo , Proliferação de Células , Criança , Pré-Escolar , Citocinas/metabolismo , Síndrome de Down/complicações , Síndrome de Down/epidemiologia , Feminino , Humanos , Ligante Coestimulador de Linfócitos T Induzíveis/metabolismo , Lactente , Infecções/complicações , Infecções/epidemiologia , Ativação Linfocitária , Masculino , Receptor de Interferon alfa e beta/genética , Receptor de Interferon alfa e beta/metabolismo , Receptores de Interferon/genética , Receptores de Interferon/metabolismoRESUMO
Trisomy 21-driven transcriptional alterations in human thymus were characterized through gene coexpression network (GCN) and miRNA-target analyses. We used whole thymic tissue--obtained at heart surgery from Down syndrome (DS) and karyotipically normal subjects (CT)--and a network-based approach for GCN analysis that allows the identification of modular transcriptional repertoires (communities) and the interactions between all the system's constituents through community detection. Changes in the degree of connections observed for hierarchically important hubs/genes in CT and DS networks corresponded to community changes. Distinct communities of highly interconnected genes were topologically identified in these networks. The role of miRNAs in modulating the expression of highly connected genes in CT and DS was revealed through miRNA-target analysis. Trisomy 21 gene dysregulation in thymus may be depicted as the breakdown and altered reorganization of transcriptional modules. Leading networks acting in normal or disease states were identified. CT networks would depict the "canonical" way of thymus functioning. Conversely, DS networks represent a "non-canonical" way, i.e., thymic tissue adaptation under trisomy 21 genomic dysregulation. This adaptation is probably driven by epigenetic mechanisms acting at chromatin level and through the miRNA control of transcriptional programs involving the networks' high-hierarchy genes.
Assuntos
Biomarcadores/análise , Síndrome de Down/genética , Regulação da Expressão Gênica , Redes Reguladoras de Genes , Genômica/métodos , MicroRNAs/genética , Timo/metabolismo , Síndrome de Down/imunologia , Síndrome de Down/patologia , Feminino , Perfilação da Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Lactente , Masculino , Prognóstico , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Timo/imunologia , Timo/patologiaRESUMO
A terapia de fotobiomodulação tem sido vastamente utilizada em cultura de fibroblastos com o objetivo de se verificar seu real efeito na cicatrização de feridas e de se estabelecer os melhores parâmetros de luz. Pacientes com síndrome de Down (SD) possuem alta prevalência da doença periodontal (DP) e importantes alterações imunológicas, as quais podem interferir no processo de cicatrização. O objetivo do presente estudo foi de avaliar os efeitos da utilização de Laser e LED em fibroblastos gengivais de pacientes com e sem SD (FSD e FGH, respectivamente), verificando a viabilidade celular e o processo In vitro de cicatrização de feridas. As células foram cultivadas em placas de 96 poços (1x103 célula/poço) e colocadas em estado de aquiescência (meio DMEM com 1% de soro fetal bovino) 24h antes da irradiação e retomando sua condição inicial de 10% de soro fetal bovino (SFB) instantes antes da aplicação de Laser (AlGaAs - 660nm e AlGaInP - 810nm) e LED (637 ±15nm) com exceção do controle negativo (C-) que continuou com 1% de SFB. Os grupos foram divididos em: C+ (sem irradiação, 10% SFB), C- (sem irradiação, 1% SFB), LIV5 (5 J/cm2 por 3s), LIV8 (8 J/cm2 por 5s), LV5 (5 J/cm2, por 3s), LV8 (8 J/cm2 por 5s), LED3 (0,03 J/cm2 por 3s) e LED5 (0,05J/cm2 por 5s). A potência utilizada foi a mesma tanto para o Laser como para o LED (40mW). A viabilidade celular foi avaliada através dos testes colorimétricos MTT e Cristal Violeta, nos períodos de 24,48,72 e 96h. O teste de cicatrização de feridas In vitro (placas de 24 poços) para avaliação da migração dos fibroblastos, foi nos períodos de 12, 24, 36 e 48h. A análise estatística foi realizada através do teste ANOVA de medidas repetidas complementado pelo teste de Tukey (p<0,05). Os grupos experimentais, em grande parte dos períodos, obtiveram melhor viabilidade celular em relação ao C+, com exceção do grupo LIV8 que apresentou crescimento celular próximo de zero, em todos os períodos. Para FSD os melhores resultados foram com LIV5, LED3 e LED5 (p<0,05), enquanto que para FGH, foi o LV5 (p>0,05). No ensaio de cicatrização de feridas os melhores resultados foram LIV5 para FGH (p<0,05) e todos os tratamentos com exceção do LIV8 para FSD (p<0,05). Os FSD apresentaram maior fechamento da ferida em relação ao FGH nos períodos de 24 e 36h (p<0,05). Como conclusão, a fotobiomodulação por Laser e LED mostrou ser efetiva para viabilidade celular, tanto para o FGH como para o FSD, com exceção do Laser infravermelho de maior densidade de energia e maior tempo de exposição (LIV8). Na migração celular, a fotobiomodulação foi efetiva no maior fechamento da ferida para os FSD. Logo, a terapia de fotobiomodulação por Laser e LED, com os parâmetros adequados, parecer ser um tratamento adjuvante promissor para pacientes com SD.(AU)
The photobiomodulation therapy has been widely used in fibroblast culture in order to verify its effects on wound healing and to establish the best parameters of light. Down's syndrome patients (DS) present high prevalence of periodontal disease (PD) and important immunological changes, which could interfere on the wound healing process. The aim of this study was to evaluate the Laser and LED effects on gingival fibroblasts cultures from patients with or without DS (FSD and FGH, respectively), through cell viability tests and in vitro wound healing test. Cells were grown in 96-well plates (1x103 cells / well) and then, put in a quiescence environment, (DMEM medium with 1% fetal bovine serum) for 24 hours before irradiation. After that an initial condition of 10% fetal bovine serum (FBS) was set before Laser (Red -AlGaAs - 660nm and Infrared - AlGaInP - 810nm) and LED (637 ± 15nm) application, with the exception of the negative control (C-) which still remained with 1% FBS. The groups were divided in: C+ (no irradiation, 10% FBS), C (no irradiation 1% FBS), LIV5 (5J/cm2 for 3s), LIV8 (8 J / cm2 for 5s), LV5 (5J/cm2 for 3s), LV8 (8J/cm2 for 5s), LED3 (0.03J/cm2 for 3 seconds) and LED5 (0,05J / cm2 for 5s). The power output was the same for both Laser and LED (40mW). Cell viability was evaluated through MTT and Crystal Violet colorimetric tests, in periods of 24,48,72 and 96h. The in vitro wound healing assay (24 well plates), measured the fibroblasts migration, during 12, 24, 36 and 48 hours. Statistical analysis was performed using repeated measures ANOVA complemented by Tukeys test (p <0.05). The experimental groups, in most periods, presented higher cell viability compared to C+, except for the LIV8 group that exhibited cell growth near to zero, in all periods. In relation to FSD, the best results were with LIV5, LED 3 and LED 5 (p<0.05), while to FGH, the LV5 presented higher viability (p<0.05). The best results for the wound healing test were LIV5 for FGH (p<0,05) and all groups but LIV8 for FSD (p<0,05). FSD cells presented higher wound closure in relation to FGH at 24 and 36h (p<0,05). In conclusion, the Laser and LED photobiomodulation was effective for cell growth, for both FGH and FSD cells, except for the infrared laser with higher energy density and longer exposure time (LIV8). Photobiomodulation was more effective for wound closure by FSD cells. Therefore, laser and LED photobiomodulation therapy, with appropriate parameters, seems to be a promising adjunctive treatment for patients with DS.(AU)
Assuntos
Humanos , Síndrome de Down/imunologia , Fibroblastos/efeitos da radiação , Gengiva/citologia , Lasers Semicondutores/uso terapêutico , Terapia com Luz de Baixa Intensidade/métodos , Cicatrização/efeitos da radiação , Análise de Variância , Movimento Celular/efeitos da radiação , Proliferação de Células/efeitos da radiação , Sobrevivência Celular/efeitos da radiação , Células Cultivadas , Formazans , Reprodutibilidade dos Testes , Sais de Tetrazólio , Fatores de TempoRESUMO
Individuals with Down syndrome (DS) have a high incidence of immunological alterations with increased susceptibility to bacterial and viral infections and high frequency of different types of hematologic malignancies and autoimmune disorders. In the current study, we profiled the expression pattern of 92 immune-related genes in peripheral blood mononuclear cells (PBMCs) of two different groups, children with DS and control children, to identify differentially expressed genes that might be of pathogenetic importance for the development and phenotype of the immunological alterations observed in individuals with DS. PBMCs samples were obtained from six DS individuals with karyotypically confirmed full trisomy 21 and six healthy control individuals (ages 2-6 years). Gene expression was profiled in duplicate according to the manufacturer's instructions provided by commercially available TaqMan Human Immune Array representing 92 immune function genes and four reference genes on a 96-plex gene card. A set of 17 differentially expressed genes, not located on chromosome 21 (HSA21), involved in immune and inflammatory pathways was identified including 13 genes (BCL2, CCL3, CCR7, CD19, CD28, CD40, CD40LG, CD80, EDN1, IKBKB, IL6, NOS2 and SKI) significantly down-regulated and four genes (BCL2L1, CCR2, CCR5 and IL10) significantly up-regulated in children with DS. These findings highlight a list of candidate genes for further investigation into the molecular mechanism underlying DS pathology and reinforce the secondary effects of the presence of a third copy of HSA21.
Assuntos
Síndrome de Down/imunologia , Criança , Pré-Escolar , Cromossomos Humanos Par 21/genética , Síndrome de Down/genética , Feminino , Humanos , Masculino , TranscriptomaRESUMO
JUSTIFICATIVA E OBJETIVO: A síndrome de Down (SD) é a anormalidade cromossômica mais comum em recém-nascidos (RN) vivos. Em virtude do maior conhecimento sobre todos os aspectos que envolvem a síndrome de Down, nas duas últi- mas décadas a expectativa de vida das pessoas com síndrome de Down mais que dobrou. Ela representa um desafio para o clínico, devido aos diversos e complexos problemas de saúde que os acometem e o atendimento adequado ao paciente necessita de conhecimento atualizado sobre as suas principais intercorrências, que apresenta algumas particularidades relacionadas ao sistema imune. O objetivo deste estudo foi rever os principais problemas de saúde relacionados ao sistema imunológico do paciente com SD, bem como atualizar o clínico sobre os novos conhecimentos da síndrome de Down. CONTEÚDO: Foram consultadas as bases de dados para a busca dos artigos recentes e relevantes sobre a resposta imunológica do paciente com sín- drome de Down. No presente artigo, são abordados temas que focam a atenção no cuidado ao paciente adulto com síndrome de Down tais como infecções recorrentes, respostas às vacinas, doenças autoimunes e outros assuntos relacionados à resposta imunológica dessas pessoas. CONCLUSÃO: Devido à maior expectativa de vida, um número crescente de pessoas adultas e idosas com síndrome de Down será atendido por todas as especialidades médicas, tornando-se necessária uma constante atualização sobre a síndrome. Em relação ao sistema imunológico, o clínico deve ter especial atenção com infecções, resposta vacinal diminuída e maior prevalência de doenças autoimunes.(AU)
BACKGROUND AND OBJECTIVE: Down syndrome (DS) is the most common chromosomal abnormality in live newborns. Due to the greater knowledge of all aspects involving DS, in the last two decades the life expectancy from people with Down syndrome more than doubled. It represents a challenge to physicians due to the diverse and complex health problems that affects this patient and the proper care needs current knowledge about its main complications, which presents some particularities related to the immune system. The objective of this study was to review the major health problems related to the immune system of patients with Down syndrome, also to update the physician on the new clinical knowledge in Down syndrome. CONTENTS: We consulted databases for the search of relevant and recent articles on the subject. In the present manuscript, issues are addressed with focus on attention in the care of adult patients with Down syndrome among which we highlight the recurrent infections, responses to vaccines, autoimmune diseases, as well as other matters related to the immune response of these individuals. CONCLUSION: Due to the longer life expectancy, a growing number of adults and elderly patients with Down syndrome will be attended by all medical specialties, requiring the acquisition of more knowledge about this syndrome. Regarding the immune system, the physician should pay special attention to infections, decreased vaccine response and a higher prevalence of autoimmune diseases.(AU)
Assuntos
Humanos , Infecções Respiratórias , Doenças Autoimunes , Vacinas/imunologia , Expectativa de Vida , Síndrome de Down/imunologiaRESUMO
BACKGROUND: It has been reported that vaccination against hepatitis B is less effective among people with Down syndrome than in the general population. We aimed to evaluate the rate of seroconversion to hepatitis B vaccine in children with Down syndrome from Brazil. METHODS: A total of 120 people with Down syndrome were included. All of them received the vaccine at intervals of 0, 30 and 180 days and serum samples were tested for the presence of antibodies to the hepatitis B surface antigen (anti-HBs) 30 days after the last dose. RESULTS: In the studied group, 58.3% (70/120) were male and 41.7% (50/120) female, with the median age of 5 years (range 2-15 years). Fifty-eight of 120 (48.3%) developed anti-HBs after vaccination. No association was found between gender and/or age and vaccine response. CONCLUSIONS: The low rate of seroconversion in response to hepatitis B vaccine suggests that all patients with Down syndrome immunized against hepatitis B should be followed and monitored by clinicians.
Assuntos
Síndrome de Down/imunologia , Vacinas contra Hepatite B/administração & dosagem , Hepatite B/prevenção & controle , Adolescente , Brasil/epidemiologia , Criança , Pré-Escolar , Relação Dose-Resposta Imunológica , Síndrome de Down/epidemiologia , Feminino , Humanos , Esquemas de Imunização , MasculinoRESUMO
Down syndrome (DS) is the most common chromosomal abnormality among live-born infants. Respiratory tract infections are the most important cause of mortality in individuals with DS at all ages. In recent decades several studies have been performed to elucidate abnormalities of the immune system in DS. Non-immunological factors, including abnormal anatomical structures, congenital heart disease and gastro esophageal reflux, may play a role in the increased frequency of respiratory tract infections. Addressing immunological and non-immunological factors involved in the pathogenesis of infectious diseases may reduce the susceptibility to infections in DS children.
Síndrome de Down (SD) es la anormalidad cromosómica más común entre los recién nacidos vivos. Las infecciones respiratorias son la causa más importante de mortalidad en individuos con SD en todas las edades. En las últimas décadas se han realizado varios estudios para aclarar las anormalidades del sistema inmune en SD. Factores no-inmunológicos, incluyendo estructuras anatómicas anormales, enfermedad cardíaca congénita y reflujo gastroesofágico, pueden desempeñar un papel en el aumento de la frecuencia de infecciones del tracto respiratorio. Abordar los factores inmunológicos y no inmunológicos implicados en la patogenia de las enfermedades infecciosas puede reducir la susceptibilidad a las infecciones en los niños SD.
Assuntos
Humanos , Criança , Infecções Respiratórias/etiologia , Infecções Respiratórias , Síndrome de Down/complicações , Síndrome de Down/imunologia , Imunidade Adaptativa , Imunidade Inata , Infecções Respiratórias/imunologia , Infecções Respiratórias/prevenção & controleRESUMO
BACKGROUND: Individuals with Down syndrome (DS) have a higher prevalence and severity of periodontal disease, which cannot be explained by poor oral hygiene alone and is related to changes in the immune response. The aim of this study is to evaluate whether DS was associated with differential modulation of expression of genes associated with proinflammatory and anti-inflammatory responses in periodontal disease. METHODS: A total of 51 individuals were evaluated: 19 individuals with DS and periodontal disease (group 1), 20 euploid individuals with periodontal disease (group 2; positive control), and 12 euploid individuals without periodontal disease (group 3; negative control). Clinical periodontal evaluation and gingival biopsies were performed. Quantitative reverse transcription-polymerase chain reaction was used to determine expression levels of interleukin-10 (IL-10), the receptors IL-10RA and IL-10RB, intracellular adhesion molecule 1 (ICAM-1), interferon-γ-inducible protein 10 (IP-10), and the signaling intermediates Janus kinase 1, signal transducer and activator of transcription 3 (STAT-3), and suppressor of cytokine signaling 3 (SOCS-3). RESULTS: Expression of IL10, SOCS3, IP10, and ICAM1 mRNA in DS patients was significantly lower compared to euploid individuals with periodontal disease, whereas IL-10RB and STAT-3 mRNA levels were higher in individuals with DS. CONCLUSION: Reduced expression of IL-10 coupled with a possible increase of STAT3 activation (increase of STAT3 and reduction of SOCS3 mRNA) indicates an important modulation of the immune response, with attenuation of anti-inflammatory and increase of proinflammatory mediators. This modulation may be related to the increased prevalence and severity of periodontitis in individuals with DS.