Submitted by Silvana Teresinha Dornelles Studzinski (sstudzinski) on 2015-10-19T17:55:48Z No. of bitstreams: 1 NELSON MANOEL DE MOURA QUEVEDO_.pdf: 1744806 bytes, checksum: faaf5521ba9ca9a40ca45be29cfd07c2 (MD5) / Made available in DSpace on 2015-10-19T17:55:48Z (GMT). No. of bitstreams: 1 NELSON MANOEL DE MOURA QUEVEDO_.pdf: 1744806 bytes, checksum: faaf5521ba9ca9a40ca45be29cfd07c2 (MD5) Previous issue date: 2015-08-19 / UNISINOS - Universidade do Vale do Rio dos Sinos / Avanços em computação ubíqua estão permitindo o surgimento de oportunidades em diversas áreas, entre elas está a área da saúde. Nessa área surgem diversas aplicações que utilizam computação ubíqua para cuidados com a saúde, chamadas de aplicações de Cuidados Ubíquos. Conforme pesquisa realizada, foram encontrados vários modelos que possibilitam cuidados ubíquos para os usuários, tais como planejamento alimentar, controle de ingestão de alimentos calóricos, sugestão de restaurantes, acompanhamento diário dos alimentos ingeridos e suporte na seleção de menus conforme restrições para uma dieta segura. Entretanto, nenhum dos modelos considerados fornece suporte de maneira ubíqua a usuários que sofrem de alergia alimentar. Assim, a proposta deste trabalho é a de desenvolver um modelo ubíquo, baseado em ciência de situação, de detecção de risco de ingestão dos oito ingredientes alergênicos (soja, ovo, leite, trigo, peixe, crustáceo, amêndoas oriundas de árvores e amendoim) e seus derivados, que são responsáveis por mais de 90% dos casos de alergias alimentares. A maior contribuição do modelo Allergy Detector para a comunidade científica consiste em empregar a ciência de situação para o propósito específico de dar suporte a usuários na área de alergia alimentar. Além disso, o modelo apresenta também uma importante contribuição para a sociedade, dando suporte a usuários que sofrem de alergia aos oito principais alergênicos, apontando as proteínas contidas nesses alimentos ou em seus derivados, sendo essas informações obtidas da base dados apresentada no site da União Internacional de Sociedades de Imunologia (WHO/IUIS). Utilizou-se o modelo de Endsley como base para poder-se aplicar a técnica de ciência de situação, que a partir da utilização dos contextos de perfil e de localização, somados à correlação desses dois contextos, permite realizar as inferências necessárias. E que a partir da correlação desses dois contextos, o modelo consegue identificar se existem pratos com alergênicos à saúde do usuário. Essa correlação só é possível graças à ontologia criada, que armazena todas as informações sobre os pratos e ingredientes desses pratos do restaurante identificado, bem como as informações das proteínas alergênicas contidas nos oito principais alergênicos. O modelo proposto teve três avaliações, sendo uma avaliação através de um estudo de caso, outra quanto ao desempenho do aplicativo e uma terceira avaliação relativa à usabilidade do modelo. Para o estudo de caso utilizou-se o protótipo criado e confirmou-se a expectativa de que a aplicação de ciência de situação, baseada no modelo de Endsley, possibilitaria que o modelo de forma ubíqua detectasse riscos ao usuário da presença de alergênicos nos pratos servidos nos restaurantes. Enquanto que para avaliação do desempenho, coletou-se os tempos médios de respostas para requisições entre os principais serviços, bem como mediu-se o consumo de CPU durante os conjuntos de requisições aplicadas, constando-se que o tempo médio de resposta cresce linearmente até um determinado número de requisições e após isso apresenta um comportamento exponencial e quanto ao consumo de CPU, constatou-se que os serviços pouco oneraram as plataformas PaaSs. Como última avaliação mediu-se a usabilidade do modelo através de experimentos de campo com 10 voluntários, que atestaram que o modelo atendeu a todos os construtos medidos e a partir dos resultados de análise estatística, pode-se confirmar que o modelo de medição proposto é coerente com as Hipóteses identificadas sobre influência entre construtos. / Advances in ubiquitous computing are enabling the emergence of opportunities in many areas, among them is the health area. In this area emerge many applications using ubiquitous computing for health care, called Ubiquitous Healthcare applications. According to survey conducted, have been found many models that enable ubiquitous healthcare to users, such as food planning, control intake of high-calorie foods, restaurant suggestions, daily monitoring of the diet and support in the selection menus as restrictions for safe diet. However, none of the models concerned provides support ubiquitous way for users who suffer from food allergies. Thus, this paper proposes to develop a ubiquitous model based on situation awareness, of risk detection intake of the eight major allergens (soy, egg, milk, wheat, fish, crustacean, trees nuts and peanuts) and their derivate, which causes about 90% of cases of all food allergies. The biggest model contribution to the scientific community consists of using the situation awareness for the specific purpose of supporting users in food allergy area. In addition, the model presents too an important contribution for society, supporting users who suffer from allergy to eight major allergens, presenting proteins contained in these foods or its derivatives, and that information obtained from the database hosted on the Union International Immunology Societies (WHO / IUIS) website. Was used the Endsley´s model as base to apply the situation awareness technique, which from the use of the profile and location contexts, added to the correlation of these two contexts, allows to perform the necessary inferences. And that from the correlation of these two contexts, the model is able to identify if there are dishes with allergens to the user's health. This correlation is only possible due to the ontology created, which stores all the information about the dishes and ingredients in these dishes the restaurant identified as well as the information of allergenic proteins contained in the eight major allergens. The proposed model had three evaluations, the first as an assessment by a case study, another on the application performance and a third evaluation on the usability of the model. For the case study were used the prototype created and confirmed the expectation that the situation awareness application, based on the Endsley´s model, would enable the model ubiquitously detect hazards to the user of the presence of allergens in food served in restaurants. While for performance evaluation, were collected the average response times for requests among the main services, and was measured CPU consumption during the sets applied requests, stating that the average response time increases linearly up a number of requests and thereafter presents an exponential behavior, and as the CPU consumption, it was found that the service used PaaSs platforms bit. As a final evaluation measured the usability of the model through field experiments with 10 volunteers, who testified that the model met all the measured constructs and from the results of statistical analysis, it can be confirmed that the proposed measurement model is consistent with the hypotheses identified on influence among constructs.

The prevalence of food allergies is a growing concern in the United States. Approximately 8% of the pediatric population has some form of food allergy. Many of these children are either in the preschool and primary school setting, which is where the majority of allergic reactions occur. If the symptoms of a food allergy reaction are not treated within minutes of exposure, the results can be damaging or fatal. Evidence continues to demonstrate that preschool and school personnel do not feel trained or prepared should a severe reaction arise. The purpose of this evidence-based project was to determine if the implementation and instruction of food allergy guidelines and an educational in-service program on the treatment of food allergies would increase the knowledge and ability of preschool personnel to respond should a reaction occur. The adult learning theory of Knowles and Bandura's theory of self-efficacy were the theoretical frameworks for this project. This project incorporated a 40-minute educational in-service along with the introduction of food allergy guidelines including an emergency action plan and epinephrine auto-injector training. A pretest and posttest were administered prior to and following the educational in-service, respectively. A paired sample t test revealed there was a dramatic increase in knowledge following the educational in-service about food allergy management, recognition, and treatment. Preschool personnel felt more empowered to react should a food allergy reaction occur. By teaching preschool-personnel about food allergies, they will have the necessary resources that will support the creation of a safer environment for children challenged with food allergies.

Made available in DSpace on 2015-05-14T12:59:59Z (GMT). No. of bitstreams: 1 arquivototal.pdf: 2254071 bytes, checksum: 5ef1f814625ed46426cc35ec211b8399 (MD5) Previous issue date: 2013-03-27 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / Root bark infusions of the plant Cissampelos sympodialis Eichl (Menispermaceae) are used in folk medicine, in Northeast Brazil, for the treatment of diseases of the respiratory and digestive tracts. Previous studies showed that the hydroalcoholic extract of the leaves (AFL) of the plant and warifteine (W), alkaloid bisbenzylisoquinolinic, presented anti-inflammatory and anti-allergic effects. This study evaluated the effect of the oral treatment of mice with W and methyl warifteine (MW) in the paw edema formation induced by phlogistic agents, vascular leakage and cell migration in acute inflammatory models and the effect of oral treatment with AFL and its alkaloids (W and MW) in chronic inflammation represented by the experimental model of food allergy (BALB / c mice sensitized with ovalbumin - OVA). Oral treatment with W reduced the paw edema induced by carrageenan, histamine and prostaglandin E2, an effect not presented in MW treatment. The warifteine and methyl-warifteine also reduced the vascular leakage, however without inhibiting cell migration associated with inflammation. In the experimental model of food allergy the treatment with W induced weight gain in animals with decreased of diarrhea. Methylation of warifteine did not induce weight gain nor inhibited allergic diarrhea during the allergen challenge. However treatment with AFL did not induce weight gain nor inhibited allergic diarrhea. In contrast, treatment with the AFL or its alkaloids reduced the IgE specific for ovalbumin (OVA) titer, increased the proportion of CD4 + or CD8+ T lymphocytes in mesenteric lymph nodes. The proportion of regulatory T lymphocytes in the mesenteric lymph nodes was also increased by the treatments. In vitro experiments, with cells from mesenteric lymph nodes of sensitized animals, demonstrated that W and MW inhibited the secretion of interleukin (IL-) 12 and IL-10 with no change in the interferon-γ (IFN-γ) and IL- 13 levels. These results demonstrated that the oral treatment with warifteine presented anti-inflammatory activity by inhibiting the action of mediators of inflammation and the methylation of the molecule did not improve this effect. Also, the treatment with AFL, W and MW showed immunomodulatory effects in food allergy with increased of Treg cells and decreased of cytokines derived from cells of the innate immune mechanism independent of that of the adaptive immune mechanism. / Infusões das raízes da planta Cissampelos sympodialis Eichl (Menispermaceae) são utilizadas, pela medicina popular, no Nordeste Brasileiro, para o tratamento de doenças do trato respiratório e digestório. Estudos prévios demonstram que o extrato hidroalcoólico das folhas (AFL) da planta e a warifteina (W), alcaloide bisbenzilisoquinolínico, apresentam efeitos anti-inflamatórios e antialérgicos. Esse estudo avaliou, portanto, o efeito do tratamento oral de camundongos com W e a metil-warifteina (MW) na formação do edema de pata induzido por agentes flogísticos, no extravasamento vascular e na migração celular em modelos de inflamação aguda e o efeito do tratamento oral com a AFL e seus alcaloides (W e MW) na inflamação crônica representada pelo modelo experimental de alergia alimentar (camundongos BALB/c sensibilizados com ovalbumina - OVA). O tratamento com a W reduziu o edema de pata induzido por carragenina, por histamina ou prostaglandina E2, efeito esse não observado com o tratamento com MW. A warifteina e a metil-warifteina também reduziram o extravasamento vascular, contudo sem inibir a migração celular associada à inflamação. No modelo experimental de alergia alimentar o tratamento com W induziu ganho de peso dos animais com diminuição da diarreia. A metilação da warifteina, embora não tenha induzido o ganho de peso diminuiu a diarreia durante os desafios com o alérgeno. Todavia o tratamento com AFL não induziu o ganho de peso e nem inibiu a diarreia alérgica. Diferentemente, os tratamentos com o AFL e com os alcaloides reduziram os títulos de IgE específica para ovalbumina (OVA), aumentaram a proporção de linfócitos T CD4+ e CD8+ no linfonodo mesentérico. A proporção de linfócitos T reguladores foi aumentada no linfonodo mesentérico pelos tratamentos em estudo. Os experimentos in vitro, com células do linfonodo mesentérico de animais sensibilizados, demonstraram que W e MW inibiram a secreção de interleucina (IL-)12 e IL-10, sem alteração nos níveis de interferon-γ (IFN-γ) e IL-13. Esses resultados demonstraram que o tratamento oral com warifteina apresentou atividade anti-inflamatória por inibir a ação de mediadores da inflamação e que a metilação da molécula não potencializou seu efeito. Também, os tratamentos com AFL, W e MW apresentaram efeitos imunomoduladores na alergia alimentar com aumento de células Treg e com diminuição de citocinas oriundas de células do mecanismo imune inato independente das do mecanismo imune adaptativo.

A hipersensibilidade a alimentos é comum em crianças e adultos. O camarão, apesar de muito apreciado, é um alimento potencialmente capaz de desencadear reações alérgicas em indivíduos geneticamente predispostos. O principal alérgeno em camarão é a tropomiosina. O objetivo desse experimento foi avaliar os efeitos da radiação gama na reatividade IgE a tropomiosina de camarão da espécie Litopenaeus vannamei e avaliar as modificações físico-químicas e sensoriais no produto, induzidas por esse processo. As amostras foram constituídas de camarões sem o cefalotórax, descongelados e liofilizados, submetidos a diferentes doses de radiação gama: 0 (test.), 5, 10 e 15 kGy. Utilizou-se para a irradiação um irradiador multipropósito, semi-industrial de 60 Co. A taxa de dose empregada foi de 7,5 kGy/hora. Determinou-se a reatividade IgE utilizando as técnicas: ELISA e \"Imunobloting\". Foram realizados testes físico-químicos e sensoriais, para verificar a viabilidade do produto após a irradiação. Os dados obtidos foram submetidos à análise de variância (ANOVA) e teste de Tukey (p<=0,05). As doses de radiação gama aplicadas nesse experimento não alteraram de forma significativa a reatividade IgE, a cor, o colesterol, teor de ácidos graxos e a aceitação dos camarões. Concluiu-se que a radiação gama nessas doses, apesar de não causar modificações que comprometam a qualidade do produto, não pode ser indicada para o controle de alérgenos em camarões, por ter apresentado baixo impacto na modificação da estrutura protéica alergênica / The hypersensitivity to foods is common in children and adults. The shrimp in spite of very appreciated is a food potentially capable to unchain allergic reactions genetically in individuals per disposed. The major allergen in shrimp is the tropomiosin. The aim of this study was to evaluate the effects of gamma irradiation on IgE reactivity to shrimp tropomyosin (Litopenaeus vannamei) and evaluate the physical and chemical changes and sensory product, induced by this process. The samples will be constituted of thawed and freeze-dried shrimp submitted to different radiation doses: 0 (test.), 5, 10 and 15 kGy. Was used for irradiating an irradiation multipurpose semi-industrial sector. 60 Co. The dose rate used was 7.5 kGy / hr. The samples, later to the irradiation, they will go by analyses for allergens determination using the techniques: ELISA and Imunobloting. Acceptance test will be done to verify physic-chemical and sensorial attributes after irradiation. Datas will be evaluated by ANOVA and Tukey test (p<=0.05). The gamma radiation doses applied in this experiment did not change significantly IgE reactivity, color, cholesterol, fatty acid content and the acceptance of shrimp studied. It was concluded that the gamma radiation in these doses, although not causing changes that compromise the quality of the product cannot be indicated for control of allergens in shrimp because it presented a low impact on allergenic protein structure modification

Abstract The aim of the South Karelian Allergy Research Project (SKARP) was to quantify the occurrence of children’s food allergy and food-associated hypersensitivity symptoms and their associated factors. The study population comprised all children born between April 2001 and March 2006 and living in the province of South Karelia, in the south-eastern part of Finland. The questionnaire survey was conducted in co-operation with the child health clinics in the area in 2005&#8211;2006. Concurrently with but independently of the questionnaire study, the results of allergy tests regarding the same child population were collected from patient records. The participation rates in the questionnaire study were 54% (644/1194) among the newborn infants and 69% (3308/4779) among the children aged 1 to 4 years. The lifetime prevalence of parent-reported food allergies was 9% and that of parent-perceived food-associated hypersensitivity symptoms 21% by the age of 4 years. In addition, another 19% of children adhered to an elimination diet without previous symptoms associated with any food items. The prevalence of children with such diets decreased by age. Up to the age of 4 years, 19% of the participants had undergone a food allergy test and 8% of the participants had obtained a positive result in these tests. Physician-diagnosed food allergies and food allergies based on the tests were more common for milk, egg and cereals than for other food items. The tested children and those with a positive test result were only slightly overrepresented among the participants. Allergic manifestations in either biological parent doubled and in both biological parents tripled the incidence of a positive food allergy test. The spring season coinciding with the end of the first trimester of pregnancy predicted sensitisation to food items in the children. In early childhood, food allergies and food hypersensitivities were found to be common in a child population. New population-based knowledge regarding the inheritance of these conditions was obtained. Additionally, an association was observed between the timing of the 11th gestational week in spring and the sensitisation to food items, the detailed reasons and immunological mechanisms of which must be confirmed in further studies. / Tiivistelmä Etelä-Karjalan allergiatutkimus (EKAT) käynnistettiin selvittämään lasten ruoka-allergioiden ja ruokayliherkkyysoireiden esiintyvyyttä ja niihin liittyviä tekijöitä. Tutkimusväestöön kuuluivat kaikki ne Etelä-Karjalan maakunnan alueella asuvat lapset, jotka olivat syntyneet huhtikuun 2001 ja maaliskuun 2006 välisenä aikana. Kyselyaineisto kerättiin yhteistyössä alueen neuvoloiden kanssa vuosina 2005&#8211;2006. Kyselytutkimuksen kanssa samanaikaisesti mutta siitä riippumattomasti kerättiin samaa lapsiväestöä koskevat allergiatestitulokset alueen potilasrekistereistä. Kyselytutkimuksen osallistumisaste oli vastasyntyneiden ikäluokassa 54&#160;% (644/1194) ja isommilla lapsilla 69&#160;% (3308/4779). Kolmannen ikävuoden loppuun mennessä vanhemmat ilmoittivat 9&#160;%:lla lapsista todetun ruoka-allergiaa ja lisäksi 21&#160;%:lla ruokayliherkkyys perustui ainoastaan vanhempien havaintoihin. Näiden lisäksi 19&#160;% lapsista vältti yhtä tai useampaa ruoka-ainetta ilman, että minkään ruoka-aineen olisi todettu aiheuttaneen oireita. Dieettien noudattajien osuus väheni selvästi tarkasteltaessa ikäluokkia yksivuotiaista neljävuotiaisiin. Kolmannen ikävuoden loppuun mennessä ruoka-allergiatestattuja oli 19&#160;% ja positiivisen testituloksen saaneita 8&#160;% tutkimukseen osallistuneista. Lääkärin toteamat ja testeihin perustuneet ruoka-allergiat olivat tavallisempia maidolle, kananmunalle ja viljoille kuin muille ruoka-aineille. Allergiatestatuilla ja positiivisen testituloksen saaneilla oli vain lievä yliedustus kyselytutkimukseen osallistujien joukossa verrattuna kyselyyn vastaamattomiin. Allergiset sairaudet toisella biologisella vanhemmalla kaksinkertaistivat ja molemmilla vanhemmilla kolminkertaistivat positiivisen ruoka-allergiatestin ilmaantuvuuden. Raskauden ensimmäisen kolmanneksen lopun ajoittuminen kevääseen ennakoi syntyvän lapsen herkistymistä ruoka-aineille. Varhaislapsuuden ruoka-allergioiden ja -yliherkkyyksien todettiin olevan tavallisia väestössä. Näiden sairauksien periytyvyydestä saatiin uutta väestötietoa. Lisäksi havaittiin yhteys 11. raskausviikon ajoittumisen kevääseen ja ruoka-aineille herkistymisen välillä. Yhteyden yksityiskohtaiset syytekijät ja immunologiset mekanismit täytyy ehdottomasti vahvistaa jatkotutkimuksin.

Food-related diseases, including food allergies and food intolerances, are on the rise worldwide. According to the World Health Organisation (WHO), allergic diseases in the economically advanced countries of the WHO have become the largest child environmental epidemic. Dysregulation of immune tolerance is the basic mechanism involved in the development of food allergy. It is believed that the risk of developing allergies is more related to other lifestyle factors such as a diet, physical activity or obesity. Food allergies in children and adult populations vary both in the spectrum of triggering foods and also their symptoms and their severity. The prognosis also differs in allergies for different types of foods. One of the most important factors affecting the correct development of the baby's immune system is nutrition. In the first 4 - 6 months, the baby should only receive breast milk - for infants it is the most appropriate and allergenically safe diet. It strengthens their immune system. Its positive effect is observed especially on the occurrence of food allergies and atopic eczema. However, developing asthma and other allergies may not be prevented. Breastfeeding has an extraordinary importance and benefits in preventing many illnesses for both the child and the mother. Milk is a major food...

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Background: Lifestyle and environmental factors are known to contribute to allergic disease development, especially very early in life. However, the link between diet composition and allergic outcomes remains unclear. Methods: In the present population-based cohort study we evaluated the dietary intake of 10-year-old children and analyses were performed with particular focus on atopic dermatitis or food allergy, allergic diseases known to be affected by dietary allergens. Dietary intake was assessed via semi-quantitative food frequency questionnaires. Based on these data, individual nutrient intake as well as children’s Dietary Inflammatory Index (C-DIITM) scores were calculated. Information about atopic manifestations during the first 10 years of life and confounding factors were obtained from standardized questionnaires during pregnancy and annually thereafter. Results: Analyses from confounder-adjusted logistic regression models (n = 211) revealed that having atopic outcomes was associated with having a pro-inflammatory pattern at the age of 10 years: OR = 2.22 (95% CI: 1.14–4.31) for children with atopic dermatitis and OR = 3.82 (95% CI: 1.47–9.93) for children with food allergy in the first 10 years of life Conclusion: A pro-inflammatory dietary pattern might worsen the atopic outcome and reduce the buffering capacity of the individual against harmful environmental exposures or triggers. For pediatricians it is recommended to test for the individual tolerance of allergenic foods and to increase the nutrient density of tolerable food items to avoid undesirable effects of eating a pro-inflammatory diet.

La prévalence des allergies alimentaires IgE-médiées aurait triplé au cours de la dernière décennie avec des études Nord-Américaines atteignant les 8% chez les enfants. Quoiqu’il n’y ait à ce jour aucun traitement curatif pour les allergies alimentaires, l’immunothérapie oral (OIT) constitue une nouvelle approche expérimentale prometteuse. Cette dernière consiste en l’administration de doses progressive d’allergènes par voie orale sur une période prolongée dans le but d’instaurer un état de désensibilisation et possiblement une tolérance orale soutenue. Cette approche a été démontrée sécuritaire et permettrait la désensibilisation à haute dose de plus de 80% des participants allergiques aux arachides, lait ou œufs. Dans cette thèse, nous présentons 2 études de phase 1 portant sur des protocoles d’OIT, destinés à optimiser l’efficience du traitement chez les sujets avec allergies alimentaires multiples. Près de 30% des enfants avec allergie alimentaire sont allergiques à plus d’un aliment, une proportion qui augmente à 70% lorsqu’on considère les cas les plus sévères. Ces enfants sont à risque augmenté de réactions accidentelles et souffrent d’un impact plus grand sur leur qualité de vie. Dans la première étude, en créant un mélange individualisé avec un ratio stochiométrique 1:1 entre les protéines des aliments allergiques de l’enfant, nous démontrons qu’il est possible de désensibiliser jusqu’à 5 aliments simultanément avec un profil d’innocuité similaire à une monothérapie. Dans la seconde étude, nous utilisons un traitement à l’omalizumab, un anticorps monoclonal anti-IgE, pour permettre une désensibilisation orale multi-allergénique fortement accélérée. Lorsque comparé à l’approche sans omalizumab, ce protocole s’associe à une nette diminution du temps requis pour atteindre les doses d’entretien, passant d’une médiane de 21 à 4 mois, sans affecter le profil d’innocuité. Alors que ces études fournissent des approches cliniques raisonnables pour désensibiliser la population multi-allergique, plusieurs questions persistent, notamment en ce qui a trait à l’induction de tolérance permanente. Une barrière majeure à cet égard réside dans notre piètre compréhension des mécanismes sous-jacents à l’immunothérapie. Prenant avantage d’échantillons cliniques bien caractérisés provenant des essais cliniques ci-haut mentionnés, nous utilisons les nouvelles technologies de séquençage TCR pour suivre la distribution clonale des lymphocytes T spécifiques aux arachides durant une immunothérapie orale. Nous démontrons que l’OIT s’associe à des changements significatifs dans les fréquences des clones spécifiques, suggérant un processus d’épuisement clonal et de remplacement. Nous démontrons par ailleurs que le test de prolifération lymphocytaire, traditionnellement utilisé pour évaluer la réponse cellulaire allergique, est dominé par une distribution polyclonale hautement non-spécifique. Cette observation a des implications majeures considérant que la plupart de la littérature actuelle sur la réponse T se base sur cette technique. En somme, cette thèse jette les bases pour des programmes de recherche translationnelle pour optimiser et personnaliser les protocoles cliniques actuels et développer de nouvelles avenues d’investigation et de traitement pour améliorer la prise en charge des sujets avec allergies alimentaires. / The prevalence of IgE-mediated food allergies has tripled over the last decade with prospective studies indicating that up to 8% of children may be affected in North America. There is currently no cure for food allergy but oral immunotherapy (OIT) is an experimental approach to treat food allergies. It consists in the progressive administration from minute to large amounts of the allergenic food by the mouth over a prolonged period of time to induce a state of desensitization and possibly sustained tolerance. This approach has been shown to be safe and to allow desensitization to high doses in over 80% of participants allergic to peanuts, milk or egg. In this thesis, we present two phase 1 trials on OIT protocols designed to efficiently treat multiple foods allergies. About 30% of children with food allergy are allergic to more than one food. This proportion increases to 70% when considering the most severe cases. Children with multiple food allergies are at higher risk of accidental reactions and suffer from greater impact on quality of life than those with single food allergies. By creating a customized treatment mix with a 1:1 stoichiometric ratio for the child’s relevant food proteins, we were first able to safely desensitize up to 5 foods simultaneously with a safety profile similar to single allergen therapy and a minimal increase in time to maintenance. Then, taking advantage of recent evidence showing that omalizumab, an anti-IgE receptor monoclonal antibody, can significantly raise reaction thresholds in food allergic subjects, we used short courses of omalizumab to allow very rapid oral desensitization to various foods in a second phase 1 study. When compared to “standard” multi-OIT, the omalizumab-enabled rush protocol resulted in a decreased time to maintenance from a median of 21 to 4 months. While these studies provide reasonable clinical approaches to this population, many questions remain, especially with regards to long term tolerance. A major limit to our progress in improving these protocols stems from our lack of understanding of the underlying immune mechanisms of oral immunotherapy. Taking advantage of well phenotyped samples from the afore-mentioned trials, we used next-generation high-throughput TCR sequencing to follow clonal distribution of peanut specific T cells during oral immunotherapy. We found that OIT is associated with significant changes in food-specific clonal frequencies, suggesting clonal exhaustion and replacement as an underlying mechanism of OIT. In addition, we show that the proliferation assay which is traditionally used to assess the cellular response is dominated by a highly non-specific polyclonal distribution. This observation has important implications considering most of the current literature on T cell response to immunotherapy is based on this assay. This highlights the need for the development of new tools to assess the cellular allergic response. Overall this thesis lays the ground for further comprehensive translational research programs on the treatment of food allergy.

Made available in DSpace on 2016-04-26T20:21:46Z (GMT). No. of bitstreams: 1 Maria Cecilia Cury Chaddad.pdf: 2206986 bytes, checksum: 82564a4366fdadb6ebbc1aee18a566f3 (MD5) Previous issue date: 2013-06-11 / This study aim to protect the rights to health and adequate food of the population with food allergy, estimated at about 8% of children and 3% to 5% of adults, arguing there is a need for the provision of information about allergens on product labels, as well as along consumers service assistance (such as electronic websites and phone numbers). It is pointed the interrelationship between the right to health and right to life as well as that between the right to health and the right to adequate food, rights whose effective protection depend on the consumers access to information. The relevance of the topic regarding the right to information about the presence of allergens and feasibility of the proposal of the obligation of allergens labeling are demonstrated through the analysis of existing standards relating to food labeling in Brazil, as well as which treatment given to the issue of labeling of allergens in comparative law. Finally, on the premise that people with food hypersensitivity need to maintain a diet that excludes the presence of allergens, as a way to ensure their well-being and their life with dignity, it is pointed to the State's responsibility to protect the rights to health and to adequate food of this portion of the Brazilian population, with the regulating of the duty of providing information about the presence (or absence) of such substances in food available for consumption for part of the food industry, although this presence give up unintentionally (traces), which depends on compliance with good manufacturing practices for food products and careful risk assessment / Este trabalho objetiva tutelar os direitos à saúde e à alimentação adequada da população com alergia alimentar, estimada em cerca de 8% das crianças e entre 3% e 5% dos adultos, sustentando a necessidade de que haja a disponibilização de informações a respeito de substâncias alérgenas nos rótulos dos produtos, assim como junto aos canais de atendimento ao consumidor (como sítios eletrônicos e telefones). Como fundamentação, aponta para a inter-relação existente entre o direito à saúde e o direito à vida, assim como aquela existente entre o direito à saúde e o direito à alimentação adequada, direitos cuja tutela efetiva dependem do acesso à informação por parte dos consumidores. A relevância do tema, atinente ao direito à informação quanto à presença de alérgenos e a viabilidade da proposta de rotulagem obrigatória, é demonstrada a partir da análise das atuais normas relacionadas à rotulagem de alimentos no Brasil, assim como qual o tratamento conferido ao tema da rotulagem de alérgenos no direito comparado. Por fim, partindo da premissa de que as pessoas com hipersensibilidade alimentar necessitam manter uma dieta que exclua a presença de alérgenos, como forma de se garantir o seu bem-estar e sua existência digna, aponta-se a responsabilidade do Estado em proteger os direitos à saúde e à alimentação adequada desta parcela da população brasileira, através da regulamentação do dever de disponibilização de informações quanto à presença (ou ausência) de tais substâncias nos alimentos disponibilizados ao consumo por parte das indústrias alimentícias, ainda que tal presença se dê de forma involuntária (traços), o que depende da observância de boas práticas de produção de produtos destinados à alimentação e criteriosa avaliação de riscos