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Humanos , Asma , Terapêutica , Produtos Biológicos , Doença , Guias como Assunto , Síndromes de ImunodeficiênciaRESUMO
O presente guia apresenta revisão extensa sobre imunobiológicos utilizados, liberados e ainda sob estudo, para o tratamento da asma, doenças alérgicas e imunodeficiências. Além das características físico-químicas de alguns desses fármacos, são revisadas as indicações e os resultados de estudos clínicos realizados para avaliar eficácia e segurança. Separados por doença específica, são apresentados os principais agentes disponíveis e aprovados para utilização segundo as normas regulatórias nacionais.
This guide presents an extensive review of immunobiological drugs used, approved and/or under investigation for the treatment of asthma, allergic diseases and immunodeficiencies. In addition to the physicochemical characteristics of some of these drugs, their indications and results of clinical studies evaluating efficacy and safety are reviewed. The main agents available and approved for use in each specific disease according to national regulatory standards are presented.
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Humanos , Asma , Sinusite , Terapia Biológica , Proteínas Recombinantes de Fusão , Dermatite Atópica , Angioedemas Hereditários , Omalizumab , Hipersensibilidade Alimentar , Urticária Crônica , Anafilaxia , Anticorpos Monoclonais , Segurança , Terapêutica , Produtos Biológicos , Preparações Farmacêuticas , Doença , Eficácia , Citocinas , Regulamentação Governamental , Alergia e Imunologia , Síndromes de Imunodeficiência , ImunoterapiaRESUMO
BACKGROUND: Inflammation is the most relevant mechanism linking obesity with insulin-resistance and metabolic disease. It impacts the structure and function of tissues and organs involved in metabolism, such as the liver, pancreatic islets and the hypothalamus. Brown adipose tissue has emerged as an important component of whole body energy homeostasis, controlling caloric expenditure through the regulation of non-shivering thermogenesis. However, little is known about the impact of systemic inflammation on the structure and function of brown adipose tissue. METHODS: The relations between IL10 and mitochondria structure/function and also with thermogenesis were evaluated by bioinformatics using human and rodent data. Real-time PCR, immunoblot, fluorescence and transmission electron microscopy were employed to determine the effect of IL10 in the brown adipose tissue of wild type and IL10 knockout mice. FINDINGS: IL10 knockout mice, a model of systemic inflammation, present severe structural abnormalities of brown adipose tissue mitochondria, which are round-shaped with loss of cristae structure and increased fragmentation. IL10 deficiency leads to newborn cold intolerance and impaired UCP1-dependent brown adipose tissue mitochondrial respiration. The reduction of systemic inflammation with an anti-TNFα monoclonal antibody partially rescued the structural but not the functional abnormalities of brown adipose tissue mitochondria. Using bioinformatics analyses we show that in both humans and mice, IL10 transcripts correlate with mitochondrial lipid metabolism and caspase gene expression. INTERPRETATION: IL10 and systemic inflammation play a central role in the regulation of brown adipose tissue by controlling mitochondrial structure and function. FUND: Sao Paulo Research Foundation grant 2013/07607-8.
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Tecido Adiposo Marrom/citologia , Inflamação/patologia , Interleucina-10/genética , Mitocôndrias/patologia , Estremecimento/genética , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Marrom/patologia , Animais , Caspases/genética , Linhagem Celular , Temperatura Baixa , Biologia Computacional/métodos , Metabolismo Energético , Técnicas de Inativação de Genes , Humanos , Inflamação/genética , Inflamação/metabolismo , Metabolismo dos Lipídeos , Masculino , Camundongos , Mitocôndrias/genética , Mitocôndrias/metabolismo , Proteína Desacopladora 1/metabolismoRESUMO
[This corrects the article DOI: 10.3389/fped.2018.00230.].
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We report a novel homozygous JAK3 mutation in two female Brazilian SCID infants from two unrelated kindreds. Patient 1 was referred at 2 months of age due to a family history of immunodeficiency and the appearance of a facial rash. The infant was screened for TRECs (T-cell receptor excision circles) and KRECs (kappa-deleting recombination excision circles) for the assessment of newly formed naïve T and B cells respectively, which showed undetectable TRECs and normal numbers of KRECs. Lymphocyte immunophenotyping by flow cytometry confirmed the screening results, revealing a T-B+NK- SCID. The patient underwent successful HSCT. Patient 2 was admitted to an intensive care unit at 8 months of age with severe pneumonia, BCGosis, and oral moniliasis; she also had a positive family history for SCID but newborn screening was not performed at birth. At 10 months of age she was diagnosed as a T-B+NK- SCID and underwent successful HSCT. JAK3 sequencing revealed the same homozygous missense mutation (c.2350G>A) in both patients. This mutation affects the last nucleotide of exon 17 and it is predicted to disrupt the donor splice site. cDNA sequencing revealed skipping of exon 17 missing in both patients, confirming the predicted effect on mRNA splicing. Skipping of exon 17 leads to an out of frame deletion of 151 nucleotides, frameshift and creation of a new stop codon 60 amino acids downstream of the mutation resulting in a truncated protein which is likely nonfunctional.
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BACKGROUND: Food allergy (FA) prevalence has increased in the last decades, but epidemiologic studies could show overestimated results. The objective of this study is to estimate the prevalence of immediate FA in adults in a region of Central Brazil, using a questionnaire to try to reduce misperceptions about FA reaction. METHODS: A cross-sectional study was conducted, enrolling an adult population aged 18-65 years comprised of families in a Central Brazilian city. In the first phase, participants answered a self-administered questionnaire for FA screening. In the second phase, the participants who reported an FA in the first questionnaire were visited to complete the second questionnaire applied by trained researchers. RESULTS: Of the 4,916 adults visited, 1,583 returned a completed questionnaire. Reported FA occurred in 171 (10.8%) subjects, and the more frequent citations were cow's milk, pork, fruits, shrimp, and vegetables. One hundred and four of these individuals completed the second questionnaire, and 15 (1.0%) were considered to have an FA diagnosis. The main foods were fruits, followed by cow's milk, shrimp, pork, and vegetables. CONCLUSION: After use of a specific questionnaire to recognize possible IgE-mediated FAs, a low frequency of FA was considered in this population. Use of a directed questionnaire administered by trained researchers could be an alternative for epidemiological IgE-mediated FA studies to achieve more accurate results.
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Hipersensibilidade Alimentar/epidemiologia , Adolescente , Adulto , Idoso , Viés , Brasil/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Vigilância da População , Prevalência , Inquéritos e Questionários , Adulto JovemRESUMO
BACKGROUND: This study was designed to analyze spirometric parameters and cytokine (interferon [IFN] gamma and IL-5) levels in induced sputum from patients with asthma or allergic rhinitis (AR) and nonatopic subjects. METHODS: Thirty-three subjects aged 18-60 years were enrolled in the present study. Eight patients had asthma without AR symptoms, 16 had AR without asthma symptoms or history, and both groups had positive skin-prick test (SPT) to aeroallergens. The nine remaining subjects were healthy nonatopic subjects with negative SPT to aeroallergens. Spirometry was performed by evaluating the forced vital capacity (FVC), forced expiratory volume in the 1st second (FEV(1)), and forced expiratory flow between 25 and 75% (FEF(25-75)) of FVC before and after bronchodilator use. Induced sputum samples were also collected for measuring cytokine (IFN-gamma and IL-5) levels by enzyme-linked immunosorbent assay. RESULTS: Significant pre- and postbronchodilator change was observed only for FEV(1) with higher variation values in asthmatic subjects compared with patients with AR (p < 0.05) and nonatopic subjects (p < 0.01). There was no significant difference in pre- and postbronchodilator spirometric parameters among the three groups, although asthmatic patients showed lower prebronchodilator FEF(25-75) values (p = 0.065). IL-5 levels were higher in induced sputum from patients with asthma and AR compared with nonatopic subjects (p = 0.020 and p = 0.032, respectively), but IFN-gamma levels showed no significant difference between the groups. CONCLUSION: Spirometric measurements were not able to show any occurrence of bronchial constriction in patients with AR, but predominant IL-5 levels in induced sputum from these patients reinforce the role of Th2-type immune response in lower respiratory airways that could contribute to the concept of "one airway, one disease."
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Antígenos de Dermatophagoides/imunologia , Asma/diagnóstico , Interleucina-5/metabolismo , Rinite Alérgica Perene/diagnóstico , Escarro/metabolismo , Adulto , Animais , Asma/imunologia , Asma/fisiopatologia , Feminino , Humanos , Interferon gama/metabolismo , Interleucina-5/genética , Masculino , Pessoa de Meia-Idade , Pyroglyphidae/imunologia , Rinite Alérgica Perene/imunologia , Rinite Alérgica Perene/fisiopatologia , Espirometria , Equilíbrio Th1-Th2RESUMO
Allergic rhinitis (AR) is a public health problem with high prevalence worldwide. We evaluated levels of specific IgE, IgA, and IgG4 antibodies to the Dermatophagoides pteronyssinus (Dpt) house dust mite and to its major allergens (Der p1 and Der p2) in serum and saliva samples from allergic and nonallergic children. A total of 86 children were analyzed, from which 72 had AR and 14 were nonallergic healthy children. Serum IgE and serum/salivary IgG4 levels to Dpt, Der p1, and Der p2 were higher in allergic children whereas serum/salivary IgA levels to all allergens were higher in nonallergic children. IgE levels positively correlated with IgG4 and IgA to all allergens in allergic children, while IgA levels negatively correlated with IgG4 to Dpt and Der p1 in nonallergic children. In conclusion, mite-specific IgA antibodies predominate in the serum and saliva of nonallergic children whereas mite-specific IgE and IgG4 are prevalent in allergic children. The presence of specific IgA appears to have a key role for the healthy immune response to mucosal allergens. Also, specific IgA measurements in serum and/or saliva may be useful for monitoring activation of tolerance-inducing mechanisms during allergen specific immunotherapeutic procedures, especially sublingual immunotherapy.
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Proteínas Sanguíneas/metabolismo , Dessensibilização Imunológica , Imunoglobulina A/metabolismo , Imunoglobulina E/metabolismo , Imunoglobulina G/metabolismo , Rinite Alérgica Perene/imunologia , Proteínas e Peptídeos Salivares/metabolismo , Adolescente , Animais , Antígenos de Dermatophagoides/imunologia , Antígenos de Dermatophagoides/metabolismo , Proteínas de Artrópodes/imunologia , Proteínas de Artrópodes/metabolismo , Biomarcadores Farmacológicos/metabolismo , Proteínas Sanguíneas/imunologia , Criança , Cisteína Endopeptidases/imunologia , Cisteína Endopeptidases/metabolismo , Dermatophagoides pteronyssinus/imunologia , Epitopos/metabolismo , Feminino , Humanos , Imunidade Humoral , Imunidade nas Mucosas , Imunoglobulina A/imunologia , Imunoglobulina E/imunologia , Imunoglobulina G/imunologia , Masculino , Rinite Alérgica Perene/diagnóstico , Rinite Alérgica Perene/terapia , Proteínas e Peptídeos Salivares/imunologiaRESUMO
BACKGROUND: This study was designed to analyze spirometric parameters and cytokine (interferon [IFN] gamma and IL-5) levels in induced sputum from patients with asthma or allergic rhinitis (AR) and nonatopic subjects. METHODS: Thirty-three subjects aged 18-60 years were enrolled in the present study. Eight patients had asthma without AR symptoms, 16 had AR without asthma symptoms or history, and both groups had positive skin-prick test (SPT) to aeroallergens. The nine remaining subjects were healthy nonatopic subjects with negative SPT to aeroallergens. Spirometry was performed by evaluating the forced vital capacity (FVC), forced expiratory volume in the 1st second (FEV1), and forced expiratory flow between 25 and 75% (FEF25-75) of FVC before and after bronchodilator use. Induced sputum samples were also collected for measuring cytokine (IFN-gamma and IL-5) levels by enzyme-linked immunosorbent assay. RESULTS: Significant pre- and postbronchodilator change was observed only for FEV1 with higher variation values in asthmatic subjects compared with patients with AR (p < 0.05) and nonatopic subjects (p < 0.01). There was no significant difference in pre- and postbronchodilator spirometric parameters among the three groups, although asthmatic patients showed lower prebronchodilator FEF25-75 values (p = 0.065). IL-5 levels were higher in induced sputum from patients with asthma and AR compared with nonatopic subjects (p = 0.020 and p = 0.032, respectively), but IFN-gamma levels showed no significant difference between the groups. CONCLUSION: Spirometric measurements were not able to show any occurrence of bronchial constriction in patients with AR, but predominant IL-5 levels in induced sputum from these patients reinforce the role of Th2-type immune response in lower respiratory airways that could contribute to the concept of "one airway, one disease."
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Introdução: A deficiência de anticorpos antipolissacaride ou deficiência parcial de anticorpos é considerada uma dasquatro imunodeficiências mais comuns da infância e sua principal manifestação são as infecções bacterianas repetitivas das vias aéreas.Descrição: São relatados casos de três pacientes com historta de infecções de repetição de diferentes evoluções cujaavaliação imunológica demonstrou uma produção alterada de anticorpos ao Streptococcus pneumoniae após imunização para os sorotipos testados, embora apresentasse níveis normais deimunoglobulinas, cuja instalação de um tratamento adequado promoveu a redução nas infecções bem como da qualidade de vida desses pacientes.Comentários: A grande maioria dos pacientes com deficiência de anticorpos antipolissacaride necessita de tratamento antibiótico agressivo nas infecções, cursos de antibióticos profiláticos, e em alguns casos, de terapia de reposição de imuneglobulinas.Alguns pacientes podem se beneficiar da vacinação heptavalente conjugada para o S.pneumoniae. É necessárioampliar a informação médica com relação ao diagnóstico apresentadonessa série, bem como, melhorar a rede laboratorial de propedêutica diagnóstica para permitir a identificação dessa patologia.
Introduction: Impaired polysaccharide responsiveness or partial antibodies defect is considered one of the four mostcommon immunodeficiencies in pediatric patients and is characterized by recurrent bacterial respiratory infectlons.Description: Three cases are related with a recurrent infections history with different evaluations, which immunological evaluations showed impaired antibodies response againstStreptococcus pneumoniae after immunization for tested serotypes,although presented normal leveis of immunoglobulin. The adequate treatment reduced the number and severity of infections and improved the patient's quality of life.Comments: The majority of patients with impaired polysaccharide responsiveness require aggressive antibiotic treatmentduring infections, serres of prophylactic antibiotics, and, rarely, IgG replacement. Some patients may clinicai benefit from írnmunization with the conjugate vaccine to S.pneumoniae. It'simportant to improve the medical information about the presenteddiagnosis, in addition to amplify the number of practiced laboratories to better identification of this disease.
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Humanos , Masculino , Feminino , Criança , Técnicas de Diagnóstico do Sistema Respiratório , Alótipos de Imunoglobulina , Síndromes de Imunodeficiência , Infecções Pneumocócicas , Vacinas Pneumocócicas , Métodos , MétodosRESUMO
Objetivo: Estudar a abordagem aos quadros de sibilância infantil no pronto socorro de um Hospital Terciário. Métodos: Foi realizado estudo de coorte transversal, descritivo, com análise das Guias de Atendimento de Emergência (GAE) de pacientes atendidos durante a primeira semana de julho de 2003, sendo selecionadas as guias com diagnóstico de asma, bronquite, sibilância ou broncoespasmo (BE), como marcadores de sibilância e/ou crises de asma. Resultados: Do total de 1167 atendimentos, 130 foram por diagnósticos usados como marcadores de sibilância, com idades entre dois meses e onze anos. Noventa e quatro por cento das guias permitiram avaliar dados referentes à gravidade da crise, mas apenas 30
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Masculino , Recém-Nascido , Lactente , Criança , Adolescente , Humanos , Corticosteroides , Asma , Espasmo Brônquico , Serviços Médicos de Emergência , MétodosRESUMO
Objetivo: Avaliar a presença e nível dos alérgenos de Dermatophagoides pteronyssinus (Der p 1), Dermatophagoides farinae (Der f 1), Canis familiares (Can f 1), Felis domesticus (Fel d 1) e Blattella germanica (Bla g 2) em cinemas na cidade de Goiânia, GO, Brasil. Métodos: Foram coletadas amostras de poeira do chão e dos assentos da frente, do meio e do fundo de salas de cinemas, num total de 30 amostras após consentimento informado dos proprietários. A detecção dos alérgenos foi realizada pelo método ELISA.Resultados: As concentrações médias de alérgenos encontradas nos cinemas em 1g/g foram 0,35, 6,87, 0,65 e 0,07, respectivamente para Der p 1, Der f 1, Can f 1 e Fel d 1. Em nenhuma amostra foi possível a detecção de alérgenos de barata. Níveis sensibilizantes de alergénos foram observados em 76,6 per cent das amostras de Der f 1, mas também ocorreram para Der p 1 (3,33 per cent) e Can f 1 (10,0 per cent). Em 20 per cent das amostras, osníveis de Der f 1 encontrado foram superiores os considerados de risco para exacerbações das doenças alérgicas. Conclusões: As salas de cinema são ambientes fechados nas quais indivíduos susceptíveis podem entrar em contato com alérgenos e desencadearem exacerbações. Medidas para a redução dos níveis de alérgenos em locais públicos devem ser adotadas como estratégia global de controle ambiental para a melhoria da qualidade de vida em indivíduos atópicos.
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Alérgenos , Poeira , Doenças do Sistema Imunitário , Técnicas In Vitro , Pyroglyphidae , Ensaio de Imunoadsorção Enzimática , Métodos , Estudos de AmostragemRESUMO
BACKGROUND: The role of mite and pet allergens in the development of allergic diseases has been recognized for many years. OBJECTIVE: To determine mite (Dermatophagoides pteronyssinus [Der p 1] and Dermatophagoidesfarinae [Der f 1]), cat (Felis domesticus [Fel d 1]), and dog (Canis familiaris [Can f 1]) allergen levels in Brazilian private cars. METHODS: Mite, cat, and dog allergens were measured in dust samples collected from 60 upholstered seats of private vehicles using enzyme-linked immunosorbent assays. RESULTS: Mean levels of Der p 1 (0.24 microg/g of dust; range, 0.06-2.05 microg/g of dust) and Der f 1 (0.29 microg/g of dust; range, 0.06-2.07 microg/g of dust) were extremely low in most dust samples analyzed. In contrast, sensitizing mean levels of Can f 1 (1.51 microg/g of dust; range, 0.14-30.96 microg/g of dust) and Fel d 1 (0.43 microg/g of dust; range, 0.02-5.75 microg/g of dust) were observed in 32 (53%) and 12 (20%) samples, respectively. Mean Can f 1 levels were significantly higher in cars whose owners kept dogs at home (3.27 microg/g of dust) than in those without pets (0.57 microg/g of dust; P = .008). There were no significant differences in allergen levels regarding the age of the vehicle or the number of users and whether the owners transport pets inside the vehicles. CONCLUSIONS: Private cars constitute an important pet, but not mite, allergen reservoir for continuous contamination of the indoor environment. Pet allergens may be present even in cars whose owners do not have pets. Effective measures to reduce allergen exposure in cars should be taken routinely, especially for pet-allergic patients.
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Alérgenos/análise , Antígenos de Dermatophagoides/análise , Exposição Ambiental , Glicoproteínas/análise , Veículos Automotores , Animais , Antígenos de Plantas , Proteínas de Artrópodes , Brasil , Gatos , Cisteína Endopeptidases , Cães , Humanos , Hipersensibilidade/imunologiaRESUMO
Objetivo: Determinar o nível dos alérgenos de Dermatophagoies pteronyssinus (Der p 1), Dermatophagoies farinae (Der f 1), Canis familiaris (Can f 1) e Felis domesticus (Fe d 1) em veículos privados de passeio (VPP) e em veículos de transporte escolar (VT ) na cidade de Uberlândia, MG. Métodos: Foram coletadas amostras de poeira dos assentos de 60 VPP e 60 VT após consentimento informado dos proprietários e aplicação de questionários relativos às características dos veículos, propriedade e transporte de animais, bem como número de passageiros. A quantificação dos alérgenos foi realizada pelo método LISA de duplo anticorpo. Resultados: Baixos níveis de Der p 1 e Der f 1 foram detectados em ambos os tipos de veículos. Can f 1 foi o alérgeno predominante, com médias geométricas de 1,51 8g/g (IC 95: 0,99 menos 2,31 8g/g) em VPP e 1,03 8g/g (IC 95: 0,66 menos1,62 8g/g) em VT . Níveis sensibilizantes ³ mg/g de poeira) de Can f 1 foram encontrados em 32/60 (53,3) dos VPP e 36/60 (60) dos VT , enquanto níveis sensibilizantes de Fel d 1 foram detectados em 12/60 (20) dos VPP e 16/60 (27) os VT. Conclusões: Os veículos apresentam níveis sensibilizantes de alérgenos de animais domésticos, principamente Can f 1. A realização de medidas para redução desses alérgenos, haja visto a freqüência de uso desses veículos, é importante para uma adequada estratégia global de controle ambienta em pacientes atópicos.