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Karlander, Rasmus. "Allergi - en påminnelse om vårt ursprung : en kvantitativ enkätundersökning över förekomsten avallergier bland studenterna på Gymnastik & idrottshögskolan i Stockholm." Thesis, Gymnastik- och idrottshögskolan, GIH, Institutionen för idrotts- och hälsovetenskap, 2013. http://urn.kb.se/resolve?urn=urn:nbn:se:gih:diva-3147.
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Aim - To investigate the prevalence of allergies among students at The Swedish School of Sport and Health Sciences (GIH) in Stockholm and relate it to factors that previous research in this area found to influence the risk of developing allergic diseases. - Can Hygiene Hypothesis or more specifically the relationships of family structure, socioeconomic status and the degree of overcrowding explain the existence of allergies among students at GIH? - Can the prevalence of allergies among students at GIH be explained by any of the known relationship for the prevalence of allergic diseases this study has taken into account? Method - Quantitative survey of students at GIH in the fall of 2013. Results - 214 students from The Swedish School of Sport and Health Science participated in the study, with representation from the first - and last - year students of all educational programs. More than twice the proportion of those diagnosed respondents said that their mother smoked during pregnancy or while they were breast-fed compared with the same group of respondents with no allergic diagnosis. The correlation is not statistically significant (p -value: 0.054). The majority of respondents with an allergic diagnosis indicated that their home mopped once a week or more for most of their childhood, while the majority of respondents with no allergic diagnosis stated that their home mopped less often. The correlation is not statistically significant (p -value: 0.055). Almost twice the proportion of respondents with an allergic diagnosis indicated that they spent most of their childhood in a major city. Similarly, nearly double the proportion of respondents with no allergic diagnosis indicated that they spent most of their childhood in the country (p -value: 0.06). The majority of respondents with an allergic diagnosis had a younger mother at birth in comparison with respondents without any allergic diagnosis. The mean maternal age at birth was 28.3 years for respondents with an allergic diagnosis and 29.9 years for respondents with no diagnosis. Difference in mean age between the two groups is statistically significant (p-value: 0.038). Conclusions - None of the related factors the study took into account, for which earlier studies in the area shown to affect the incidence of allergic diseases could provide a convincing explanation for the prevalence of allergies among students at The Swedish School of Sport and Health Sciences. The resulting trend for the majority of the studied factors are in line with previous research. An elderly mother was found to be significantly associated with a decreased risk of having an allergic diagnosis. The result finds no support in previous research and should be investigated more thoroughly.Syfte - Att undersöka förekomsten av allergier bland studenterna på Gymnastik & idrottshögskolan i Stockholm och relatera det till faktorer som tidigare forskning på området visat påverka risken att utveckla allergiska sjukdomar. Frågeställningar - Kan hygienhypotesen eller närmare bestämt sambanden för familjestrukturen, den socioekonomiska statusen och graden av trångboddhet förklara förekomsten av allergier bland studenterna på Gymnastik & idrottshögskolan? - Kan förekomsten av allergier bland studenterna på Gymnastik & idrottshögskolan förklaras utifrån något av de tidigare kända sambanden för förekomsten av allergiska sjukdomar denna studie tagit i beaktande? Metod - Kvantitativ enkätundersökning av studenterna på Gymnastik & idrottshögskolan under hösten 2013. Resultat – 214 studenter från Gymnastik & idrottshögskolan deltog i studien med representation från första- och sista års- elever från samtliga utbildningsprogram. Mer än dubbelt så stor andel av de diagnosticerade respondenterna svarade att deras mor rökte under graviditeten eller under tiden de ammades i jämförelse med motsvarande grupp respondenter utan någon allergisk diagnos. Sam-bandet är inte statistiskt säkerställt (p-värde: 0,054). Majoriteten av respondenterna med en allergisk diagnos angav att deras hem våttorkades en gång i veckan eller oftare under större delen av deras barndom medan majoriteten av respondenterna utan någon allergisk diagnos uppgav att deras hem våttorkades mer sällan. Sambandet är inte statistiskt säkerställt (p-värde: 0,055). Nästan dubbelt så stor andel av respondenterna med en allergisk diagnos har angett att de spenderat större delen av sin barndom i en större stad. På motsvarande sätt har närmare den dubbla andelen av respondenterna utan någon allergisk diagnos uppgett att de spenderat merparten av sin barndom på landet (p-värde: 0,06). Majoriteten av respondenterna med en allergisk diagnos hade en yngre mor då de föddes i jämförelsen med respondenterna utan någon allergisk diagnos. Medelvärdet för mödrarnas ålder vid födseln var 28,3 år för respondenterna med en allergisk diagnos respektive 29,9 år för responden-terna utan någon diagnos. Skillnad i medelålder mellan de båda grupperna är signifikant (p-värde: 0,038). Slutsats – Inget av de samband studien tagit i beaktande för vilka tidigare studier på området visat sig påverka förekomsten av allergiska sjukdomar kunde ge en övertygande förklaring till förekomsten av allergier bland studenterna på Gymnastik & idrottshögskolan. Den resultatmässiga trenden för merparten av de studerade sambanden är dock i linje med tidigare forskning. En äldre mor visade sig vara signifikant associerad med en minskad risk att ha en allergisk diagnos. Resultatet finner inget stöd i tidigare forskning och bör utredas mer grundligt.
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Moreira, Sara Rios. "O paciente alérgico no consultório de medicina dentária." Master's thesis, [s.n.], 2014. http://hdl.handle.net/10284/4393.
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Projeto de Pós-Graduação/Dissertação apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Mestre em Medicina DentáriaIntrodução: A alergia é uma reação do sistema imunológico a uma série de substâncias como o pólen, o leite, o chocolate, a lã, o nylon, medicamentos e anestésicos. Afeta essencialmente indivíduos atópicos com predisposição genética. A prevalência de alergias tem vindo a aumentar na última década, estima-se que 25% da população europeia apresenta algum tipo de alergia. No consultório dentário, apesar das hipersensibilidades aos materiais dentários serem escassas, as hipersensibilidades mais comuns são as do tipo I e do tipo IV. Objetivos: Quantificar a prevalência de alergias nos pacientes atendidos na Consulta de Medicina Dentária das Clínicas Pedagógicas da Faculdade de Ciências da Saúde da Universidade Fernando Pessoa; caracterizar as alergias mais frequentes; verificar a existência de alguma relação entre a prevalência de alergias com a variável sexo e a variável idade. Metodologia: O presente estudo epidemiológico consistiu na aplicação de um inquérito como instrumento de recolha de dados quantitativos. Obteve-se uma amostra de 190 indivíduos com idade superior a 18 anos, selecionados de forma aleatória e que se dirigiram à Clinica Pedagógica de Medicina Dentária da Universidade Fernando Pessoa no ano letivo de 2013/2014. Os dados resultantes do estudo foram armazenados no programa Microsoft Excel 2010. Os procedimentos de análise estatística descritiva foram realizados utilizando o programa informático IBM SPSS Statistics. Resultados: A prevalência de alergias na população em estudo foi de 29%. A prevalência de alergias é maior no sexo feminino sendo a probabilidade (OR) de cerca de 1.89 vezes superior no sexo feminino do que no sexo masculino. No teste de correlação de Pearson, o valor observado foi de 0.302 assim não se verificou correlação entre o aumento da idade com o aumento ou diminuição das alergias. As alergias mais frequentes foi a do tipo respiratória 60%, medicamentosas 16%, doenças alérgicas com alergénios positivos 11%, do tipo cutâneas 9% e do tipo alimentares 4%. Nas alergias do tipo respiratórias observa-se uma maior percentagem na rinite alérgica com 36.40%. Relativamente às alergias do tipo medicamentosas, a penicilina apresenta 10.60%. Conclusão: A prevalência de alergias nesta população assemelha-se à de outros países Europeus. Tal como noutros países a alergia mais comum é a rinite alérgica. A análise dos resultados deste estudo pode conduzir a uma reflexão acerca do aumento da prevalência de alergias pelo que é crucial que todos os médicos dentistas tenham um cuidado extra ao abordarem os seus pacientes no sentido de diagnosticar qualquer uma das mais variadas alergias abordadas no presente trabalho. Introduction: Allergy is a reaction of the immune system to a variety of substances such as pollen, milk, chocolate, wool, nylon, drugs and anesthetics. Affects mainly atopic individuals with a genetic predisposition. The prevalence of allergies has increased in the last decade, it is estimated that 25% of the population has some type of allergy. In dental surgery, despite hypersensitivity to dental materials are rare, the most common are the hypersensitivity type I and type IV. Aims: Quantify the prevalence of allergies in patients attending at the dental medicine services of pedagogical practice in Faculdade Fernando Pessoa; characterize the most common allergies; verify the existence of any relationship between the prevalence of allergies with the gender variable and the variable age. Methodology: This epidemiological study consisted in application of a survey as a tool for collecting quantitative data. Obtained a sample of 190 individuals aged over 18 years, randomly selected and who applied to the Pedagogical Clinic of Dental Medicine, University Fernando Pessoa in the academic year 2013/2014. The data resulting from the study were stored in Microsoft Excel 2010 program. Procedures descriptive statistics were performed using the computer program SPSS Statistics. Results: The prevalence of allergies in the study population was 29%. The prevalence of allergies is higher in females and the likelihood (OR) of about 1.89 times higher in females than in males. In Pearson correlation test, the observed value was 0.302 so there was no correlation between age increase with the increase or decrease of allergies. The most common allergies of the respiratory type was 60%, 16% drug, with positive allergens allergic diseases 11%, the type Skin 9% and 4% of the food type. In the respiratory type allergies observe a higher percentage in allergic rhinitis with 36.40%. Regarding allergies drug type, penicillin has 10.60%. Conclusions: The prevalence of allergies in this population is similar to other European countries. As in other countries the most common allergy is allergic rhinitis. The results of this study may lead to a reflection on the increasing prevalence of allergies so it is crucial that all dentists take extra care when approaching their patients in order to diagnose any of the various allergies addressed in this work.
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Slovak, Andrej Jan Michal. "Laboratory animal allergy." Thesis, University College London (University of London), 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.338450.
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Oldfield, William Laurence George. "Allergen-derived T cell peptides in the treatment of cat allergy." Thesis, Imperial College London, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.398029.
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Beuraud, Chloé. "Identification et caractérisation d'une population de cellules lymphoïdes innées de type 2 (ILC2) associée à la sévérité de la rhinite allergique et de l'asthme." Thesis, Université Paris-Saclay (ComUE), 2016. http://www.theses.fr/2016SACLS475.
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Identification et caractérisation d'une population d'ILC2 associée à la sévérité de la rhinite allergique et de l'asthmeTrois catégories de cellules lymphoïdes innées (innate lymphoid cells, ILC) ont été décrites récemment sur la base de leurs phénotypes et leurs caractéristiques fonctionnelles : les ILC1, ILC2 et ILC3. Les ILC2 semblent avoir un rôle pro-inflammatoire important dans l’allergie en raison de leur capacité à produire de grandes quantités de cytokines TH2.Pour mieux comprendre le rôle de ces cellules dans l’allergie respiratoire, nous avons comparé les ILC sanguines de patients atteints d’une rhinite allergique associée ou non à un asthme, à celles de sujets non allergiques. Cette étude révèle de multiples différences fonctionnelles entre les ILC circulantes de sujets sains et allergiques. Notamment, la fréquence d’ILC2 exprimant le récepteur aux chimiokines CCR10 est augmentée dans le sang de patients asthmatiques sévères.CCR10 pouvant permettre le recrutement des ILC vers les organes cibles, le rôle des ILC2 CCR10+ dans la physiopathologie de l’asthme a été étudié. Leur présence dans les poumons humains a été observée. Des analyses fonctionnelles et phénotypiques ont révélé que cette sous-population cellulaire était peu activée mais présentait une plasticité leur conférant des caractéristiques proches des ILC1. La déplétion de ces cellules dans un modèle murin d’asthme allergique aggrave l’hyperréactivité bronchique.Les travaux de cette thèse documentent le rôle des ILC dans l’asthme. En particulier, la fréquence sanguine d’ILC2 CCR10+ augmente avec la sévérité de la maladie. Les résultats obtenus dans les modèles animaux suggèrent que ces cellules auraient un rôle bénéfique dans le contrôle de l’asthme. La voie du CCR10 pourrait représenter une nouvelle cible pour le développement de traitements innovants contre l’asthme ou une source prometteuse de biomarqueursIdentification and characterization of an ILC2 subset linked to allergic rhinitis and asthma severityInnate lymphoid cells (ILCs) have been classified into ILC1, ILC2 and ILC3 subsets based on their respective phenotypes and functions. Considering the strong ability of ILC2s to produce TH2 cytokines, these cells likely play a significant role in allergic diseases.To better understand the role of these cells in respiratory allergies, we compared blood ILCs from allergic patients with or without asthma to non-allergic individuals. Together our results show multiple functional differences between ILC from allergic and healthy subjects. In particular, ILC2s expressing the chemokine receptor CCR10 are specifically enriched in the blood of patients with severe allergic asthma.Considering that CCR10 could allow the recruitment of ILCs to target organs, the role of CCR10+ ILC2s in asthma physiopathology has been studied. This ILC2 subtype is present in human lungs. Functional and phenotypic analyses revealed that these cells are less activated than other ILC2s and show ILC1-like properties. CCR10+ ILC2s depletion in a mouse model of allergic asthma exacerbate airway hyperreactivity.Together, this work documents the role of ILCs in asthma. Specifically, circulating CCR10+ ILC2 frequency increases with asthma severity. The results obtained in mouse models suggest that these cells could have a beneficial role in asthma control. CCR10 pathway could represent a new target to elaborate breakthrough treatments against asthma or a source of promising biomarkers
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Soulsby, William Daniel III. "Greetings from the Peanut (Allergy) Gallery: Novel Treatments of Peanut Allergy." Thesis, The University of Arizona, 2012. http://hdl.handle.net/10150/244785.
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Peanut allergy is among the most prevalent and dangerous forms of allergy in today’s society. Although the physiological mechanism of peanut allergy is well understood as an IgE-mediated immunologic disorder, reasons for unbalanced proportions of this allergy across the world are not completely known. With increasing rates of peanut allergy across the world, especially in the United States, a focus on more effective treatments is essential. Currently, the two most widely used methods of treatment of peanut allergy are injectable epinephrine (EpiPen) in preventing anaphylaxis and over-the-counter antihistamines (i.e. Benadryl). However, neither of these medications is completely effective for treating the wide range of symptoms that allergic patients suffer from. Perhaps, more effective treatments can be found in novel realms, including oral immunotherapy and plasmid DNA immunization, to increase a patient’s tolerance to peanut in cases of accidental ingestion of allergen. Anti-IgE therapy is a new treatment aimed at blocking the ability of IgE to bind to mast cells, stopping IgE from mediating the release of the chemotactic and inflammatory factors that initiate the allergic reaction. Finally, new research in combined therapies for treating anaphylaxis and Chinese herbal medicines may create a new way to target a broader range of symptoms that peanut allergic patients experience during an allergic reaction.
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Gunnarsson, Nina Veetnisha. "Parenting Children with Allergy." Doctoral thesis, Hälsohögskolan, Högskolan i Jönköping, HHJ. Forskningsplattformen socialt arbete, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:hj:diva-21104.
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Mackay, Judith A. "Allergy and the neutrophil." Thesis, Imperial College London, 1989. http://hdl.handle.net/10044/1/47550.
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Ferrell, Melissa Leann. "Sublingual Immunotherapy." Diss., The University of Arizona, 2015. http://hdl.handle.net/10150/565918.
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One of the most common reasons people seek primary care and emergency care is to reduce the symptoms of allergies, such as hay fever. To meet this high demand, several recent FDA-approved methods for treating seasonal and perennial allergies have been developed, including sublingual immunotherapy tablets. Furthermore, no longer must a patient endure allergy shots; this can now be delivered sublingually. Although this method has been shown to have high safety and efficacy, very few clinicians actually utilize this form of therapy. The purpose of this paper is describe the use of sublingual immunotherapy among Nurse Practitioners (NPs) and discuss barriers that may prevent its use. Nurse Practitioners working in primary care settings were surveyed regarding their use of sublingual immunotherapy. Although many nurse practitioners treat patients with allergic disease, not one participant reported using sublingual immunotherapy. This discussion outlines some of the reasons NPs are not currently utilizing this method of allergy treatment and the findings are compared with the extant literature. This paper culminates in an evidence-based algorithm to outline best practices for utilizing sublingual immunotherapy to reduce allergy symptoms.
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Rees, Shiona Rachel. "Allergy and oral mucosal disease." Thesis, University of Glasgow, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.368579.
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Dawson, M. "Mast cell migration in allergy." Thesis, University College London (University of London), 2012. http://discovery.ucl.ac.uk/1357935/.
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The symptomology associated with allergic diseases are a direct consequence of the release of pro-inflammatory mediators from mast cells following bi- or multivalent antigen cross-linking with the high affinity immunoglobulin (Ig) E receptor, FcεR1. Chemokines, small 8-15 kDa polypeptides, control the activation and recruitment of immune cells during the allergic response. Previous studies have demonstrated that co-stimulation by the chemokine, macrophage inflammatory protein-1α (Mip-1α) and cross-linking by IgE with antigen result in four phenomenon 1) enhanced degranulation in ex vivo conjunctival mast cells and rat basophilic leukemia (RBL-2H3) cell line via its chemokine receptor (CCR) 1, cell line also referred to as RBL-CCR1; 2) arrested Mip-1α-induced chemotaxis of RBL-CCR1 cells; 3) enhanced production of proinflammatory mediators from RBL-CCR1 cells and 4) enhanced gene expression in RBL-CCR1 cells of regulatory molecules downstream of CCR1 and FcεR1 signaling pathways, Regulator of G-protein Signaling (RGS)-1 and Tribbles (TRB)- 3. It has therefore been proposed that co-engagement of CCR1 and FcεR1 affects other mast cell processes such as chemotaxis, and moreover these data indicate cross-talk between CCR1 and and FcεR1 signaling pathways. Chemotaxis of mast cells to sites of inflammation and the subsequent release of pro-inflammatory mediators are key to eliciting allergic response. Although there is a vast amount of information pertaining to the molecular mechanisms of chemotaxis in several cell types, there is very little evidence to understand mast cell chemotaxis at this level. Based on current knowledge, the main objective of this thesis was to investigate 1) the effect of CCR1 and FcεR1 co-engagement on mast cell motility and 2) the role of RGS1 and TRB3 on mast degranulation, mediator release and chemotaxis. The data obtained from this thesis is the first to demonstrate the role of WASP, CCR1 and actin polymerisation as mechanisms underlying Mip-1α induced RBLCCR1 chemotaxis, using real time microscopy. Moreover, CCR1 and FcεR1 engagement inhibits RBL-CCR1 actin cytoskeletal re-organisation and significantly increases other cell motility parameters such as directionality and Euclidean distances which are required for efficient Mip-1α-induced chemotaxis. Also, by using a murine model of allergic conjunctivitis, conjunctival mast cells accumulate in the forniceal area of an inflamed conjunctiva in comparison to non-diseased vi mice. In addition, by using siRNA the present study is also the first to show that RGS1 and TRB3 serve as negative regulators of RBL-CCR1 degranulation, mediator release and chemotaxis upon CCR1 and FcεR1 engagement. In conclusion, the data presented in this thesis could advance our understanding of the mechanisms responsible for mast cell migration and arrest during an allergic response, and hence provide new targets for anti-allergic drugs.
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Gueguen, Claire. "Caractérisation des cellules dendritiques de type 2 : Application à la recherche de biomarqueurs de l’immunothérapie spécifique allergénique." Thesis, Paris 11, 2015. http://www.theses.fr/2015PA114806.
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L’allergie ou l’hypersensibilité de type I est une réponse inappropriée du système immunitaire à une substance étrangère à l’organisme, nommée « allergène ». L’immunothérapie allergénique (ITA) est actuellement le seul traitement sur le marché qui permet de traiter l’étiologie de la maladie allergique par opposition aux traitements symptomatiques qui diminuent temporairement les manifestations allergiques. Son action consiste à réduire la sensibilité de l’organisme vis-à-vis de l’allergène en modulant progressivement la réponse immunitaire dirigée contre ce dernier. L’objectif de cette thèse était de définir des biomarqueurs d’efficacité clinique utilisables dans le cadre des traitements de l’ITA. La stratégie de recherche est basée sur une hypothèse qui consiste à suggérer que les cellules dendritiques (DCs) sont impliquées dans le succès de l’immunothérapie. En particulier, nous supposons que le traitement induit une baisse des DCs de type 2 (DC2), qui induisent des lymphocytes T auxiliaires de type 2 (TH2), et une augmentation des DCs régulatrices (DCreg), qui induisent des lymphocytes T régulateurs. La première partie de cette thèse a consisté à mettre au point des conditions de culture induisant des DC2. Pour cela, un criblage de molécules biologiques et pharmacologiques a été entrepris sur les DCs dérivées des monocytes afin d’induire in vitro des DC2 et a conduit à la mise au point d’un mélange de plusieurs molécules, dont certaines sont impliquées dans les mécanismes de l’allergie. Le phénotype des DC2 obtenu a été étudié ainsi que la polarisation des lymphocytes T induite après co-cultures en comparaison avec des DCs de type 1 (DC1) et des DCreg.La deuxième partie de cette thèse a consisté à analyser, à l’échelle moléculaire, les différents types de DCs induites (DC1, DC2 et DCreg). Pour cela, deux techniques ont été utilisées, une analyse transcriptomique par puces à ADN et une analyse protéomique par spectrométrie de masse sans marquage, pour comparer le transcriptome et le protéome des DCs induites. Le différentiel d’expression des marqueurs les plus pertinents a été validé au niveau transcriptionnel et protéique.Dans la troisième partie de cette thèse, le suivi des marqueurs dans des cellules du sang de patients allergiques traités ou non par ITA lors d’une étude clinique randomisée, contrôlée, en double aveugle, a permis de définir six nouveaux candidats biomarqueurs d’efficacité de l’immunothérapie, dont trois spécifiques des DC2 et trois autres spécifiques des DCreg. Ces marqueurs pourront être suivis lors des traitements d’ITA pour distinguer les patients répondeurs des non-répondeursAllergy or type I hypersensitivity is an inappropriate response of the immune system to a foreign substance in the body, called "allergen". Allergen immunotherapy (AIT) is currently the only treatment on the market that can handle the etiology of allergic disease versus symptomatic treatments that temporarily reduce allergic manifestations. Its action is to reduce the sensitivity of the body against allergens.The aim of this thesis was to define biomarkers of clinical efficacy of AIT. The research strategy is based on the following hypothesis: dendritic cells (DCs) are involved in the success of immunotherapy. In particular, we assume that the treatment induces a decrease in DCs type 2 (DC2), which induce type 2 helper T cells, and an increase of regulatory DCs (DCreg), which induce regulatory T cells.First, we defined optimal culture conditions inducing the polarization of in vitro immature monocyte-derived DCs (MoDCs) toward a DC2 pattern. After screening several biological and pharmaceutical agents, we selected a cocktail of six molecules with some of them are pro-allergenic molecules. The phenotype of those DC2 cells and the CD4+ T cell polarization induced after coculture were characterized extensively in comparison with type 1 DC (DC1) and DCreg.In a second part, we compared the transcriptomes and the proteomes of MoDCs polarized into DC1, DC2 and DCreg by using cDNA microarrays together with label-free mass spectrometry. The differential expression of the most relevant markers was confirmed at the transcriptional and protein level. In the third part, markers were also followed in the peripheral blood from allergic patients enrolled in a randomized, double-blind, placebo-controlled AIT study. The expression of three DC2 markers was down-regulated and of three DCreg markers was up-regulated in patients who responded to the treatment and correlated with clinical efficacy. These markers could be used as follow-up read-outs of AIT efficacy in order of to discriminate responders from nonresponders
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Kronqvist, Marianne. "Clinical and immunological studies of respiratory allergy among farmers : with focus on dust mite allergy /." Stockholm, 2000. http://diss.kib.ki.se/2000/91-628-4411-3/.
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Rundqvist, Louise. "Thermodynamical and structural properties of proteins and their role in food allergy." Doctoral thesis, Umeå universitet, Institutionen för medicinsk kemi och biofysik, 2013. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-68020.
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Proteins are important building blocks of all living organisms. They are composed of a defined sequence of different amino acids, and fold into a specific three-dimensional, ordered structure. The three-dimensional structure largely determines the function of the protein, but protein function always requires motion. Small movements within the protein structure govern the functional properties, and this thesis aims to better understand these discrete protein movements. The motions within the protein structure are governed by thermodynamics, which therefore is useful to predict protein interactions. Nuclear magnetic resonance (NMR) is a powerful tool to study proteins at atomic resolution. Therefore, NMR is the primary method used within this thesis, along with other biophysical techniques such as Fluorescence spectroscopy, Circular Dichroism spectroscopy and in silico modeling. In paper I, NMR in combination with molecular engineering is used to show that the folding of the catalytical subdomains of the enzyme Adenylate kinase does not affect the core of the protein, and thus takes a first step to linking folding, thermodynamic stability and catalysis. In paper II, the structure of the primary allergen from Brazil nut, Ber e 1, is presented along with biophysical measurements that help explain the allergenic potential of the protein. Paper III describes the need for a specific Brazil nut lipid fraction needed to induce an allergenic response. NMR and fluorescence spectroscopy is used to show that there is a direct interaction between Ber e 1 and one or several components in the lipid fraction.
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Kull, Inger. "Infant feeding and allergy in children /." Stockholm : Karolinska institutet, 2005. http://diss.kib.ki.se/2005/91-7140-553-4/.
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Admyre, Charlotte. "Exosomes in immune regulation and allergy /." Stockholm, 2007. http://diss.kib.ki.se/2007/978-91-7357-157-9/.
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Būtienė, Indrė. "Food allergy in Lithuanian birth cohort." Doctoral thesis, Lithuanian Academic Libraries Network (LABT), 2013. http://vddb.library.lt/obj/LT-eLABa-0001:E.02~2013~D_20131209_091502-26385.
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Environmental factors more often is thought to have influence in determining children’s health and development. Prevalence of allergic diseases over the last decades is increasing, especially in Western Europe. Despite lots of performed surveys it is still unclear why the prevalence of food allergy is mounting. Incidence of food allergy is age dependent and usually manifest as one of the first forms of allergy. It is considered as the first step of „atopic march“. To accurately assess the occurrence of possible risk factors for a disease that can start already in infancy and may resolve by school age, a prospective birth cohort with regular follow-up of participating children and families provides the best possible study design.
EuroPrevall birth cohort study, in which participated Vilnius University, was the first in the world investigation specially created just for evaluation of food allergy. During in this dissertation presented project for the first time real prevalence of food hypersensitivity and allergy in infants and small children in Lithuania have been determined, the most common food allergens were assessed and changes in prevalence of sensitization to them during first 30 months of life were analysed, also the role of possible determinants for the development of food allergies, such as genetic background, maternal diet during pregnancy and breastfeeding, way of birth, infections, medicines, psycho-social and environmental factors, were examined and different... [to full text]Svarbus vaidmuo, nulemiantis vaikų sveikatą ir vystymąsi, vis dažniau priskiriamas vaiką supančiai aplinkai. Sergamumas alerginėmis ligomis sparčiai didėja, o pastaraisiais dešimtmečiais jis itin išaugo, ypač Vakarų Europoje. Nepaisant daugelio atliktų tyrimų, vis dar lieka neaišku, kodėl alerginių ligų paplitimas nuolat didėja. Alergijos maistui paplitimas įvairiose amžiaus grupėse skiriasi ir yra viena iš anksčiausiai pasireiškiančių alergijos formų. Manoma, kad ji gali būti pirmasis „atopinio maršo“ žingsnis. Norint tiksliai įvertinti galimų rizikos veiksnių įtaką ligos atsiradimui, kuri gali prasidėti jau kūdikystėje ir išnykti iki mokyklinio amžiaus, tinkamiausias tyrimo metodas yra prospektyvinis naujagimių kohortos tyrimas su reguliaria į tyrimą įtrauktų vaikų ir jų šeimų stebėsena. EuroPrevall naujagimių kohorta - tai pirmasis pasaulyje tyrimas, kuriame dalyvavo ir Vilniaus Universitetas, specialiai suformuotas tik alergijos maistui ištyrimui. Šio disertacijoje pateikiamo tyrimo metu Lietuvoje pirmąkart ištirtas padidėjusio jautrumo maistui ir alergijos maistui paplitimas tarp mažų vaikų ir nustatyti dažniausiai alergiją sukeliantys maisto produktai ir sensibilizacijos maisto alergenams kaita pirmaisiais 30 gyvenimo mėnesiais, taip pat išanalizuoti tėvų ir kūdikių rizikos veiksniai, tokie kaip genetinis pagrindas, mamos mityba nėštumo metu ir žindant, gimdymo būdas, infekcijos, vartoti medikamentai, psicho-socialiniai ir aplinkos faktoriai, įtakojantys alergijos... [toliau žr. visą tekstą]
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Mont, G. C. L. du. "Food allergy in childhood atopic eczema." Thesis, University of Newcastle Upon Tyne, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.376981.
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Irander, Kristina. "An 18 year Follow-up of Allergy Development : Findings of Nasal Markers of Allergic Inflammation." Licentiate thesis, Linköping University, Linköping University, Faculty of Health Sciences, 2008. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-15853.
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Background: In addition to the family history of allergy (FH), there is a need o find objective markers of allergy development as early in life as possible in order to focus preventive measurements on high risk infants. Rhinitis problems are common causes to morbidity in adults due to allergic as well as non-allergic mechanisms. Accurate diagnoses are essential for decisions of optimal management of the patients, but in non-allergic rhinitis groups there are no objective tests to verify the diagnosis, if this is needed.
Aims: The primary aim was to evaluate the occurrence of nasal metacromatic (MC) cells during infancy as predictors for allergy development in a group of high risk subjects from birth up to 18 years of age. Additional aims were to find and evaluate nasal markers with ability to differentiate between allergic rhinitis with and without current allergen exposure from normal controls.
Subjects and methods: New-borns (n = 67) with and without family histories of allergy were included, and during the first 18 months of life occurrence of nasal MC could be evaluated in 64 infants (33 positive/31 negative MC findings). The cohort was followed up for allergy development at the ages of 18 months, 6 years and 18 years. Nasal markers as MC, nasal NO, nitrite/nitrate in nasal lavage and acoustic rhinometry at the 18-years follow-up were related to the allergic manifestations at this age.
Results: Positive nasal MC findings during infancy predicted allergy development up to 18 years of age in 31/33 subjects (94 %), as compared to 37/44 with positive FH (84 %). Negative MC findings during infancy did not exclude the risk, as 15/31 developed allergy (48 %). At the 18-years follow-up the numbers of individuals with demonstrable MC were significantly higher (p = 0.01) in the group of individuals with allergy symptoms (16/30) compared to the group of individuals with no allergy (1/12). Nasal NO levels, nitrite/nitrate concentrations in nasal lavages and acoustic rhinometry did not differentiate the allergic groups from the normal group.
Conclusions: Positive nasal MC findings during infancy predicted allergy development up to 18 years of age, and the cell findings often preceded the allergic symptoms. The marker can not be used as a single predictor of allergy development due to negative MC findings in a high proportion of allergic subjects. Positive MC findings combined with positive FH resulted in the best the risk evaluation. Differences between groups with and without current allergen exposure and healthy controls were not found by means of acoustic rhinometry, nasal MC, nasal NO or nitrites/nitrates levels. Further research to find reliable nasal markers is needed.
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Fraser, Mary Alexandra. "Clinical and serological studies of canine atopic dermatitis." Thesis, University of Glasgow, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.323423.
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Dang, Ha Xuan. "Mold Allergomics: Comparative and Machine Learning Approaches." Diss., Virginia Tech, 2014. http://hdl.handle.net/10919/64205.
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Fungi are one of the major organisms that cause allergic disease in human. A number of proteins from fungi have been found to be allergenic or possess immunostimulatory properties. Identifying and characterizing allergens from fungal genomes will help facilitate our understanding of the mechanism underlying host-pathogen interactions in allergic diseases. Currently, there is a lack of tools that allow us to rapidly and accurately predict allergens from whole genomes. In the context of whole genome annotation, allergens are rare compared to non-allergens and thus the data is considered highly skewed. In order to achieve a confident set of predicted allergens from a genome, false positive rates must be lowered. Current allergen prediction tools often produce many false positives when applied to large-scale data set such as whole genomes, and thus lower the precision. Moreover, the most accurate tools are relatively slow because they use sequence alignment to construct feature vectors for allergen classifiers. This dissertation presents computational approaches in characterizing the allergen repertoire in fungal genomes as part of the whole genome studies of Alternaria, an important allergenic/opportunistic human pathogenic fungus and necrotrophic plant parasite. In these studies, the genomes of multiple Alternaria species were characterized for the first time. Functional elements (e.g. genes, proteins) were first identified and annotated from these genomes using computational tools. Protein annotation and comparative genomics approaches revealed the link between Alternaria genotypes and its prolific saprophytic lifestyle that provides at least a partial explanation for the development of pathological relationships between Alternaria and humans. A machine learning based tool (Allerdictor) was developed to address the neglected problem of allergen prediction in highly skewed large-scale data sets. Allerdictor exhibited high precision over high recall at fast speed and thus it is a more practical tool for large-scale allergen annotation compared with existing tools. Allerdictor was then used together with a comparative genomics approach to survey the allergen repertoire of known allergenic fungi. We predicted a number of mold allergens that have not been experimentally characterized. These predicted allergens are potential candidates for further experimental and clinical validation. Our approaches will not only facilitate the study of allergens in the increasing number of sequenced fungal genomes but also will be useful for allergen annotation in other species and rapid prescreening of synthesized sequences for potential allergens.Ph. D.
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Brown, C. W. "Household dust and respiratory allergy : a study of household dust exposure and respiratory allergy in UK households." Thesis, University of Surrey, 2000. http://epubs.surrey.ac.uk/843797/.
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This thesis is designed to explore the hypothesis that settled dust in a domestic environment can contain significant levels of allergens and that common cleaning methods employed to remove dust can result in sufficient airborne exposure to potentially trigger an allergic reaction. Qualitative feedback from respondents in studies of furniture dusting habits indicated that household furniture dusting could elicit an allergic response. A consumer questionnaire was fielded to confirm the problem and it's magnitude. This indicated that it affected approximately 20% of allergy sufferers (or approximately 5% of the total UK population). Further work was performed to estimate the level of allergen exposure during dusting. Additional consumer research was fielded to ascertain the surface area being dusted, (approximately 54000cm2 for frequently dusted areas and 10000cm2 for frequently dusted areas). Domestic dusting habits were probed for the relative frequency of dusting method, which split evenly between dry dusting, wet dusting with water and wet dusting with a furniture polish. Surface sampling techniques were adapted to make in-home measurements of the rate of dust settling which was found to be approximately 3.19x10 -7 g.cm-2,day-1. In-home sampling was also undertaken to measure the mean allergen content of surface dust for major allergens, yielding 24667ng.g-1 combined dust mite, 47696ng.g-1 Fel d 1 and approximately 126 8 08ng.g-1 Can f 1. Laboratory-based studies determined the relative amount of dust rendered airborne during dusting of different furniture surface types and comparing different cleaning methods. This was found to be between 2.3- 43.0%. From these experiments, a model "average" home was constructed and used to estimate the exposure towards dust allergens during a typical dusting task. Exposure was estimated to be as much as 16500ng total dust mite, 124000 mug (31000 mU) cat allergen and 275000 ng (IU) dog allergen per dusting method. These results indicated that allergen exposure, under certain circumstances, could exceed the threshold levels that have been proposed for the onset of sensitisation.
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Palosuo, Kati. "IgE-mediated allergy to dietary gliadin studies on wheat-dependent, exercise-induced anaphylaxis and childhood wheat allergy." Helsinki : University of Helsinki, 2003. http://ethesis.helsinki.fi/julkaisut/laa/kliin/vk/palosuo/.
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Nita, Yunita. "Adverse drug reaction reporting in Australian hospitals." Thesis, Curtin University, 2002. http://hdl.handle.net/20.500.11937/1234.
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Adverse drug reactions (ADRs) are known to be a major cause of morbidity and mortality. However, only a small proportion are reported. An increase in the number and quality of reports by improving ADR reporting systems in hospitals, could improve patient outcomes and save healthcare costs. The first part of this project was to review the ADR reporting systems in Australian hospitals and to determine factors contributing to the ADR reporting rate. Data were collected by a postal, self-administered questionnaire. Questionnaires were sent to 299 chief pharmacists of Australian hospitals listed in the Society of Hospital Pharmacists of Australia (SHPA) directory. The response rate was 49.5%. Seventy seven (60%) hospitals had a formal hospital policy for ADR reporting and 110 (85.3%) hospitals targeted all drugs to be reported. ADR reporting rates to ADRAC in 2000 (ADR reports per patient admission) were between zero and 1.09% (median=0.02%) with 7.1% of hospitals having a reporting rate of zero. A centralised ADR system and the existence of an ADR policy was not associated with higher reporting rates. The next part of the project was a survey of 803 Western Australian (WA) doctors and 1323 Australian hospital pharmacists to evaluate involvement in, understanding of and reasons for reporting ADRs. A postal, self-administered, anonymous questionnaire was sent to doctors at two tertiary hospitals in Perth and three regional hospitals in WA. A similar questionnaire was sent to all hospital pharmacists listed in the membership list of SHPA, as well as non-SHPA members in WA. Response rates obtained for the WA doctors survey was 35% (n=277) and 43% (n=574) for hospital pharmacists. Sixty four percent of doctors and 96% of hospital pharmacists knew how to report ADRs within the hospital while 57% and 98% (respectively) knew how to report ADRs to ADRAC.Factors that would encourage respondents to report ADRs included serious reactions, unusual reactions, reaction to a new product and confidence in the diagnosis of the ADR. More than 70% of respondents agreed that an uncertain association between the ADR and the suspected drug, minor reactions and well known reactions were factors that would deter them from reporting ADRs. From a list of 14 hypothetical ADR questions, it was found that respondents were more likely to report serious and uncommon reactions. Finally, the incidence of cross-sensitivity between penicillin and other β-lactam antibiotics among patients experiencing penicillin allergy in Fremantle Hospital and Health Services (FHHS) was assessed, along with the appropriate documentation of penicillin allergy in the medical records. The study was a retrospective audit and review of medical records in FHHS (1994-2000). All medical records of patients experiencing penicillin allergy during admission, or causing admission to FHHS, (n=85) were reviewed and data on reactions to other β-lactams were recorded. The incidence of definite cross-sensitivity between penicillins and cephalosporins was 6%, consistent with the reported rate of cross-sensitivity. The documentation of penicillin allergy in the medical records was less than optimal, with alerts on 89% of medication charts and only 28% of medical records (front cover). Improvement in the documentation of ADRs in patients' medical records would likely decrease the risk of preventable adverse events.
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Tan, John Wei-Liang. "Induction of tolerance to egg in egg allergic children and children at high risk of egg allergy." Thesis, The University of Sydney, 2017. http://hdl.handle.net/2123/17343.
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The prevalence of food allergy has increased in recent years, placing a significant burden on individuals and families. Egg is the leading cause of IgE-mediated food allergy in infancy and early childhood in Australia, recently estimated to affect 9% of infants in an urban Australian setting. Although the natural history of egg allergy in childhood is resolution and acquisition of tolerance by teenage years in 60-75% of egg allergic infants, the burden of disease is significant in the childhood years. Previously, it was widely believed that strict avoidance of food allergens in early infancy was protective against sensitisation to food allergens, particularly in children with a genetic predisposition to atopy. For several decades, Australian, European and American Colleges of Immunology, Allergy and Paediatrics recommended avoidance of common allergic foods such as egg, wheat, nuts and fish as a method of primary prevention of food allergy. Despite these guidelines of avoidance, the incidence of food allergy has continued to increase over the last two decades. This increase in prevalence of food allergy, along with emerging evidence that early introduction of “allergenic” foods may be protective rather than sensitizing, has led to a change in guidelines for infant weaning in Australia (ASCIA), Europe (ESPGHAN) and the American Academy of Pediatrics (AAP). However, evidence from randomised controlled trials is required to substantiate early introduction of allergenic foods. The first objective of this thesis was to investigate if dietary introduction of egg into infants at risk of allergy between 4-6 months would reduce sensitization to egg. We conducted a randomized controlled trial involving infants with at least one first-degree relative with allergic disease. Infants with a skin prick test to egg white (EW-SPT) <2mm were randomized at 4 months of age to receive whole egg powder or placebo (rice powder) until 8 months of age, whilst excluding all other forms of egg in their diet. Diets were then liberalized in both groups when infants were 8 months old. The primary outcome was EW-SPT ≥3mm at age 12-months. 319 infants were recruited and randomised, 165 to the egg arm and 154 to the placebo arm. 14 infants reacted to egg within one week of introduction (despite EW-SPT <2mm at entry) and were excluded from the study. 254 infants (83%) were assessed at 12 months of age. Loss to follow up was similar between both intervention and placebo groups. Sensitization to EW at 12 months was 20% and 11% in infants randomized to placebo and egg respectively (OR=0.46, 95%CI 0.22-0.95, p=0.03, Chi-Square test). The absolute risk reduction was 9.8% (95%CI: 8.2% to 18.9%) with a number needed to treat of 11 (95%CI: 6 to 122). IgG4 to egg proteins and IgG4/IgE ratios were higher in infants who were randomized to egg (p<0.0001 for each) at 12 months. There was no effect on the proportion of children with probable egg allergy (placebo 13, egg 8). The results of this thesis demonstrates that introduction of whole-egg powder into the diets of high-risk infants reduced sensitization to egg white and induced egg-specific IgG4 (indicating immunomodulation). However 8.5% of infants randomized to egg were not amenable to primary prevention via early introduction at between 4-6 months. The results of this study mirror other recently published studies investigating early introduction of egg (STAR, STEP, PETIT), peanut (LEAP) and 6 allergenic foods (EAT). The results of the above-mentioned studies and our BEAT study will significantly contribute to the emerging body of evidence which supports early introduction of allergenic foods as primary prevention of food allergy. Children with a known food allergy, including egg allergy, have been traditionally advised to avoid all forms of the food to which they are allergic. This includes trace amounts and small amounts of modified protein in heat-treated or baked goods. It was believed, but never scientifically substantiated, that strict avoidance of food allergens would increase the likelihood and hasten the attainment tolerance to egg. Heating or enzymatic degradation can reduce the allergenicity of many proteins in part by eliminating conformational epiptopes. This is true for egg allergens, particularly ovalbumin, where heating the egg substantially changes the tertiary structure of the allergens, usually by eliminating conformation but not linear epitopes. It has been noted that some egg allergic children can tolerate baked egg but not whole egg. Apart from an oral food challenge, there is currently no other easy and reliable method of predicting if an egg allergic child will be able to tolerate baked egg without experiencing a clinical allergic reaction. There is also growing suggestion that tolerance to baked egg may hasten the outgrowing of egg allergy, although there is currently no firm evidence to support this. This second aim of this thesis was to examine the suitability of skin prick testing (SPT) to baked egg and ovomucoid in egg allergic individuals to predict the outcome of baked egg food challenges. One hundred and thirty-four egg allergic patients had SPT performed to ovomucoid and baked muffin prior to having a baked egg food challenge. Ninety of 134 patients (63%) passed the baked egg challenge. Of the 53 who reacted,
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Thang, Cin. "Investigation of intervention strategies for Ig-E mediated food allergy in a murine model of cow's milk allergy." Thesis, McGill University, 2013. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=119562.
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Food allergy, an immune-mediated adverse hypersensitivity reaction to ingested food, is an emerging global health problem that not only causes the disease to susceptible individuals but also causes psychological impacts and financial damage to their families. Food allergy incidence is significantly increased in the past decade and currently estimated at 6-8% in 1 year old children, and 2-4% in older children and adults. Food allergy is the leading cause of anaphylaxis in children and severe cases may lead to fatal anaphylaxis reactions. Although continuous efforts have been made to better understand the nature of allergens, predisposing environmental factors, and the host's immune response mechanisms, there is no cure available for food allergy today. In this study, we have investigated three food allergy reducing strategies by supplementing probiotics, low doses of allergens and omega-3 poly unsaturated fatty acids (ω-3 PUFAs) in cow's milk protein sensitized Balb/c mice. Lactobacillus rhamnosus GG (LGG) supplementation had tendency to promote Th1 response while VSL#3 provided more potent allergy reducing effects via inducing intestinal secretory IgA (sIgA). Low doses of allergen administration offered suppression of allergen-specific immune responses via Treg-mediated active suppression, indicated by suppressing both allergen-specific Th1 response [reduced BLG-specific serum IgG2a and elevated IL-12(p40)], and Th2 response [lower BLG-specific serum IgE and IgG]. Interestingly, mice received both VSL#3 and low doses of allergen exhibited both allergen-specific active suppression effects and higher sIgA production. We then investigated the effects of different levels of ω-3 and ω-6 PUFAs in the energy and fat rich Western-style diet on food allergy development. Observation of elevated BLG-specific serum immunoglobulins in all experimental mice indicated that both ω-3 and ω-6 PUFAs failed to prevent the development of allergen-specific immune response. However, ω-3 PUFAs alleviated anaphylactic reactions and the severity of allergic reaction as indicated by the unchanged rectal temperature, lower hypersensitivity scores, and Th1-favoured immune responses in BLG-sensitized O3H mice. In general, this study revealed the promising strategies for treatments and prevention against food allergy in the near future.Les allergies alimentaires, réactions dues à une hypersensibilité du système immunitaire après ingestion d'un certain type d'aliments, constituent un problème de santé publique croissant qui, en plus de dégrader la santé des individus susceptibles, engendre un impact psychologique et financier pour les familles touchées. L'incidence des allergies alimentaires a significativement augmenté ces dernières années et le taux est actuellement estimé être de 6-8% chez les jeunes enfants d'1 an et de 2-4% chez les autres enfants et les adultes. Les allergies alimentaires représentent la première cause d'anaphylaxie chez l'enfant et plusieurs cas d'allergies peuvent causer une réaction anaphylactique fatale. Bien que des efforts continus aient été faits pour tenter de mieux comprendre la nature des allergènes, les facteurs environnementaux prédisposant aux allergies et les mécanismes de la réponse immunitaire, aucun traitement contre les allergies alimentaires n'est disponible à l'heure actuelle. Dans cette étude, nous avons testé trois différentes stratégies visant à réduire l'allergie alimentaire, à savoir l'utilisation de probiotiques, de faibles doses d'allergènes et d'acides gras polyinsaturés oméga-3 chez des souris Balb/c sensibilisées aux protéines de lait de vache. L'administration de Lactobacillus rhamnosus GG (LGG) a montré une tendance à promouvoir une activation des cellules Th1 alors que VSL#3 a engendré une plus forte réduction de l'allergie via l'induction de la sécrétion intestinale d'IgA (sIgA). L'administration de faibles doses d'allergènes a provoqué une suppression de la réponse immunitaire dirigée contre les allergènes via l'activation des cellules Treg, ceci étant suggéré par la suppression des réponses immunitaires Th1 spécifique [diminution des IgG2a BLG-spécifiques et augmentation des IL-12(p40)] et Th2 spécifique [diminution des IgE et IgG BLG-spécifiques]. De plus, les souris ayant reçu à la fois VSL#3 et des faibles doses d'allergènes ont montré une suppression des effets de la réponse allergénique et une production plus élevée de sIgA. Nous avons ensuite étudié les effets de différents niveaux d'oméga-3 et d'oméga-6 dans un régime alimentaire de type occidental riche en énergie et en matières grasses sur le développement des allergies alimentaires. L'observation d'une élévation des immunoglobulines BLG-spécifiques chez toutes les souris expérimentales ont indiqué que les oméga-3 et -6 n'ont pas réussi à empêcher le développement de la réponse immunitaire dirigée contre les allergènes. Cependant, les oméga-3 ont diminué les réactions anaphylactiques et le degré de sévérité de la réaction allergique, ceci étant suggéré par un score d'hypersensibilité plus faible, une absence de changement de la température rectale et une réponse immunitaire favorisée par les cellules Th1. Pour conclure, cette étude a révélé des stratégies prometteuses pour le traitement et la prévention des allergies alimentaires dans les années à venir.
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Josefson, Anna. "Nickel allergy and hand eczema : epidemiological aspects." Doctoral thesis, Örebro universitet, Hälsoakademin, 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-11855.
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Nickel allergy is the most prevalent contact allergy and has been discussed as a possible riskfactor for hand eczema. However, hand eczema is one of the most frequently occurring skindiseases and has multifactorial origin. The aim of this thesis was to study the association between nickel allergy and hand eczema in the general population. There are only a fewpopulation-based studies previously published, that include patch testing. In addition, this thesis aimed to evaluate methods to follow the prevalence of nickel allergy.The study cohort consisted of 908 women who had been patch tested for the occurrence of nickel allergy as schoolgirls. Twenty years later, they were invited to participate in a follow-up questionnaire study. The response rate was 81%. In total, 17.6% of respondents reported handeczema after the age of 15 years and there was no statistically significant difference in the occurrence of hand eczema between those who were nickel-positive and those who were nickel negativeas schoolgirls. To further investigate possible links, another study was performed,which included a second questionnaire, a clinical investigation and patch testing. All schoolgirls from the baseline study who were still living in the area as adults were invited to participate and the participation rate was 77%. Patch test showed 30.1% nickel-positive individuals.When all participants were included in the analysis, there was no statistically significant difference between nickel-positive and nickel-negative women regarding occurrence of hand eczema. The most important risk factor for hand eczema was childhood eczema. Adjusted prevalence proportion ratio (PPR) for hand eczema after age 15 in relation to nickel patch testresults was 1.03 (95% CI 0.71--1.50) and in relation to childhood eczema 3.68 (95% CI 2.45--5.54). When women with and without history of childhood eczema were analyzed separately, the hand eczema risk was doubled in nickel-positive women without history of childhood eczema. In conclusion, the risk of hand eczema in nickel-positive women may previously havebeen overestimated. Next, the validity of self-reported nickel allergy was investigated. In the established cohort; two questions regarding nickel allergy were compared with patch test results. The validity of self-reported nickel allergy was low, and the questions regarding nickel allergy overestimated the true prevalence of nickel allergy. The positive predictive values were 59% and 60%. Another method for estimating the prevalence of nickel allergy, namely self-patch testing, was validated in the last study. In total, 191 patients from three different dermatology departments participated. The validity of self-testing for nickel allergy was adequate, with sensitivity 72%and proportion of agreement 86%.Nickelallergi är vanligt förekommande. Prevalensen i Skandinavien är 15--25% hos kvinnor och cirka 3% hos män. Sambandet mellan nickelallergi och uppkomst av handeksem har tidigare diskuterats och i vissa studier anges att 30--45% av alla individer med nickelallergi får handeksem. Det finns dock endast ett fåtal publicerade studier där personer ur normalbefolkningen har lapptestats för nickel. Handeksem ärvanligt och har ofta flera olika kombinerade orsaker. Det övergripande syftet med avhandlingen var att studera nickelallergins betydelse för uppkomst av handeksem. Detfinns ett intresse av att följa förekomsten av nickelallergi över tid, speciellt sedan det i början av 2000-talet infördes ett EU-direktiv som begränsar nickelinnehåll i klockor,smycken, metallknappar etc. Ytterligare ett syfte med avhandlingen var att utvärderaepidemiologiska metoder för att följa förekomsten av nickelallergi.Den första studien var en uppföljningsstudie av 908 flickor ur normalbefolkningen,vilka i skolåldern lapptestats med nickel. Tjugo år senare skickades en enkät till dessa kvinnor, svarsfrekvensen var hög (81%). Förekomsten av självrapporterat handeksemefter 15 års ålder var 17.6%. Det förelåg ingen signifikant skillnad i förekomst avhandeksem mellan de kvinnor som var nickelallergiska som barn jämfört med dem som inte var nickelallergiska. År 2006 utfördes ytterligare en studie, som inkluderade de kvinnor som fortfarande bodde i Örebro län. Studien omfattade en klinisk undersökning av händerna samt ett lapptest. 30% av kvinnorna var positiva för nickel.Det förelåg ingen signifikant skillnad i förekomst av handeksem mellan de som var positiva för nickel och de som var negativa. Vid separat analys av de kvinnor som angav tidigare barneksem jämfört med dem som aldrig hade haft barneksem visade det sig att risken för handeksem var dubbelt så stor hos nickelallergiker i den gruppen som aldrig hade haft barneksem. Båda studierna visade att barneksem var den största riskfaktorn för att få handeksem som vuxen, med en 3-4 gånger ökad risk. Den tredje studien var en validering av självrapporterad nickelallergi. Överensstämmelsen var låg mellan enkätfrågor gällande nickelallergi och lapptestverifierad nickelallergi. Av dem som själva bedömde sig vara nickelallergiska var endast 59% positiva enligt lapptest. För att följa förekomsten av nickelallergi i befolkningen behövs därför andra metoder. I den fjärde studien utvärderades ett självtest för nickelallergi. 191 patienter från tre olika hudkliniker i Sverige deltog i studien. Validiteten för metoden självtest var tillfredsställande, sensitiviteten var 72%och graden av överensstämmelse var 86%.
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Boupha, Prasongsidh C., of Western Sydney Hawkesbury University, Faculty of Science and Technology, and School of Food Science. "The effect of cadmium on food allergy." THESIS_FST_SFS_Boupha_P.xml, 1992. http://handle.uws.edu.au:8081/1959.7/124.
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Assessement of effects of cadium chloride exposure on the anaphylaxis reaction to food was done on six week old Swiss and BALB/c female mice. The animals were exposed to cadium as cadium chloride for either three days or six weeks. Intra-peritonal dose of cadium chloride was injected once a day, five days per week for three successive weeks. The animals were then sensitised to cow's milk by force-feeding with cow's milk for three consecutive days. Oral exposure of mice to a high dose of cadium resulted in cytotoxicity of liver and kidney cells. Retardation in growth rate and haematology change were detected. Proliferative response to the T-cell epitope from the circumsporozoite protein of plasmodium falsiparum was decreased in cultures of lymph node cells from cadium chronically treated mice and sensitised with the same peptide. In contrast, an increase of cell proliferation was observed when cow's milk was used instead. Significant increase in Immunoglobulin E level and Anaphylactic reaction dependent on the quantity of cadium exposed were recorded. No protective effect of ascorbic acid or zinc acetate on cadium alteration of immune response was observedMaster of Science (Hons) (Food Science)
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Bengtsson, Åsa. "The role of CD30 in atopic allergy /." Stockholm, 2000. http://diss.kib.ki.se/2000/91-628-4333-8/.
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Admiraal, Claudia Johanna. "Eosinophil degranulation as an allergy activation marker." [S.l. : Amsterdam : s.n.] ; Universiteit van Amsterdam [Host], 2001. http://dare.uva.nl/document/59048.
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Boupha, Prasongsidh C. "The effect of cadmium on food allergy /." Richmond, N.S.W. : Hawkesbury Agricultural College, 1994. http://library.uws.edu.au/adt-NUWS/public/adt-NUWS20030820.163219/index.html.
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Cantelmo, Jill Love. "The genetic epidemiology of asthma and allergy." Thesis, University of Oxford, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.434855.
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Hourihane, Jonathan O'Brien. "Clinical & immunological features of peanut allergy." Thesis, University of Southampton, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.242421.
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Venn, Pascal. "Interleukin-22 in human allergy and asthma." Thesis, Imperial College London, 2013. http://hdl.handle.net/10044/1/13713.
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Interleukin 22 (IL-22) is а newly-described Т helper cytokine which has been implicated in tissue regenerative processes in the gut and skin. Allergic asthma results from exposure to otherwise harmless environmental inhaled allergens that trigger Th2 Т Iymphocyte-driven IgE-аssосiаtеd immune responses in atopic individuals that contribute to airway inflammation and reversible airflow obstruction. In the long-term, this aberrant immune response is believed to increase in complexity and contribute to the permanent changes in the airways, including tissue remodelling and associated irreversible airway obstruction. In view of the known effects of IL-22 in wound healing, the overall aim of this research was to establish whether IL-22 is present in allergy and allergic asthma and to understand the influence of IL-22 on structural cells of the airway, with particular emphasis оп tissue remodelling. We, therefore, explored the presence of IL-22 and its receptors during allergen-induced late responses in the bronchi and skin and measured IL-22 production and its regulation in peripheral blood mononuclear cells (PBMCs), Т cell lines and clones derived from asthmatic bronchial muсоsa. IL-22 was increased in bгonchoalveolaг lavage after allergen inhalation in asthmatics but not in control subjects. While we were unable to reliably immunostain IL-22, its receptors were present within the cutaneous connective tissue and co-Iocalised with HSP-47, а marker of early fibrobIasts. In PBMCs, IL-22 increased after allergen stimulation whereas there was nо difference between atopics and control subjects. In Т cell lines derived from asthmatic bronchial mucosa, IL-22 was mainly found in СD4+ Т helper cells of Th1 and Th22 origin. IL-22 receptors were expressed by cultured bronchial epithelial cells, smooth muscle cells and pulmonary fibroblasts and were increased in expression in the presence of interferon-γ (IFN-γ). IL-22 was able to accelerate wound closure of bronchial epithelial cells independent of effects on cellular proliferation. Thus, IL-22 appears to be а Th1-related cytokine that may have а dual role in airway inflammation and repair.
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Gabler, Maximilian. "DNA Replicons next generation vaccines against allergy." Saarbrücken VDM Verlag Dr. Müller, 2005. http://d-nb.info/988936151/04.
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Vanhanen, Markku. "Exposure, sensitization and allergy to industrial enzymes." Helsinki : University of Helsinki, 2001. http://ethesis.helsinki.fi/julkaisut/laa/kliin/vk/vanhanen/.
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Yu, Yan. "Anti-IgE autoantibodies in bee venom allergy /." [S.l.] : [s.n.], 1991. http://www.ub.unibe.ch/content/bibliotheken_sammlungen/sondersammlungen/dissen_bestellformular/index_ger.html.
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Marti, Pamela. "New perspectives for allergy diagnosis and therapy /." [S.l.] : [s.n.], 2005. http://www.zb.unibe.ch/download/eldiss/06marti_p.pdf.
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Voor, Tiia. "Microorganisms in infancy and development of allergy : comparison of Estonian and Swedish children /." Tartu, Estonia : Tartu University Press, 2005. http://dspace.utlib.ee/dspace/bitstream/10062/1122/5/voortiia.pdf.
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SICHILI, STEFANIA. "Allergia alimentare ed Asma Bronchiale." Doctoral thesis, Università degli studi di Catania, 2013. http://hdl.handle.net/20.500.11769/490552.
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L’allergia Alimentare rappresenta una delle cause di Asma bronchiale spesso sottovalutata e poco considerata al momento della diagnosi in quanto rappresenta una piccola percentuale dei fenotipi dell’asma allergico. Lo scopo del mio studio è di valutare la prevalenza di asma bronchiale secondaria ad allergia alimentare e le loro caratteristiche, nei pazienti afferenti all’ambulatorio di Allergologia dell’Ospedale Policlinico di Catania dal mese di gennaio a dicembre 2011. Metodi: Dal mese di Gennaio al mese di Dicembre 2011 sono giunti presso il nostro ambulatorio 4544 pazienti per sospetta patologia di natura allergica. I pazienti affetti da asma bronchiale erano 1233 rappresentando quindi solo il 27 % delle utenze. Il restante 73% dei pazienti avevano effettuato una visita allergologica perché lamentavano orticaria acuta o cronica, dermatite allergica o irritativa da contatto, intolleranza al lattosio, rinite allergica ecc. Considerando il gruppo di pazienti affetti da asma bronchiale solo il 6% (75 pazienti su 1233) presentava asma da allergia alimentare all’anamnesi. La situazione clinica è stata confermata dal prick test, dalla misura delle IgE sieriche specifiche (RAST, Radio-Allergo-Sorbent Test) e dallo studio spirometrico per stabilire il grado dell’asma. Risultati: Sono stati arruolati nello studio i 75 pazienti affetti da asma bronchiale secondaria ad allergia alimentare i quali rappresentano il 6% dei pazienti del nostro ambulatorio osservate tra gennaio e dicembre 2011. Avevano un’età compresa tra i 5 ed i 65 anni, con una prevalenza per il sesso femminile (50 contro 25 maschi). Sono state prese in considerazione 5 fasce d’età: da 0-6 anni; 7-18 anni; 19-35 anni; 36-50 anni e > 50 anni. L’età compresa fra i 36-50 anni è la più rappresentativa in conformità alle utenze del nostro ambulatorio che si occupa prevalentemente di adulti. Il gruppo arruolato presentava all’anamnesi oltre l’asma conseguente all’ingestione di alimenti rinite o orticaria allergica. Nel 43% dei casi vi era associata una rinite allergica nel 8% dei casi orticaria allergica mentre nel 15 % dei casi le due comorbilità coesistevano. Nel gruppo arruolato l’anamnesi di asma da alimenti è stata confermata con i test diagnostici allergologici a nostra disposizione: il prick test ed il dosaggio delle IgE specifiche sieriche che ci hanno permesso di effettuare una distribuzione degli allergeni alimentari. In particolar modo è possibile notare che il grano è l’allergene più rappresentativo proprio perché il target d’età dei nostri pazienti appartiene ad una fascia adulta in accordo con ciò che è evidente in letteratura. Conclusioni: In questo studio i pazienti affetti da asma bronchiale da allergia alimentare sono prevalentemente di sesso femminile. Il nostro gruppo presentava all’anamnesi oltre l’asma conseguente all’ingestione di alimenti, rinite o orticaria allergica. Nel 43% dei casi vi era associata una rinite allergica nel 8% dei casi orticaria allergica mentre nel 15 % dei casi le due comorbilità coesistevano. Nel gruppo arruolato l’anamnesi di asma da alimenti è stata confermata con i test diagnostici allergologici a nostra disposizione: il prick test ed il dosaggio delle IgE specifiche sieriche. Nei nostri pazienti il grano è l’allergene più rappresentativo proprio perché il target d’età dei nostri pazienti appartiene ad una fascia adulta in accordo con ciò che è evidente in letteratura.Background: Food allergy is one of the causes of bronchial asthma often underestimated and little considered at the time of diagnosis because it represents a small percentage of the phenotypes of allergic asthma. The purpose of my study was to evaluate the prevalence of bronchial asthma secondary to food allergy and their characteristics in patients referred to hospital outpatient Allergy Hospital of Catania from January to December 2011. Methods: From January to the month of December 2011 arrived at our clinic for 4544 patients suspected of allergic disease. Patients with asthma were 1233 thus representing only 27% of the users. The remaining 73% of the patients had another allergy desease: acute or chronic urticaria, allergic dermatitis or irritant contact, lactose intolerance, allergic rhinitis etc. Considering the group of patients with asthma, only 6% (75 patients out of 1233) had asthma, food allergy anamnesis. The clinical situation was confirmed by skin prick test, the measurement of serum specific IgE (RAST, Radio-Allergo-Sorbent Test) and study spirometry to establish the degree of asthma. Results: Were enrolled in the study, 75 patients with bronchial asthma secondary to food allergy which represent 6% of patients observed. Ranged in age from 5 to 65 years, with a prevalence for females (50 versus 25 males). Have been considered five age groups: 0-6 years, 7-18 years, 19-35 years, 36-50 years and> 50 years. The aged 36-50 years is the most representative in accordance with the users of our clinic that deals mainly with adults. The asthma group had associated history of rhinitis or urticaria. In 43% of cases there was an associated allergic rhinitis in 8% of cases allergic urticaria and in 15% of cases the two coexisting comorbidities. In the group enlisted the history of asthma from food has been confirmed with allergy diagnostic tests: prick test and serum IgE. In particular, we can see that the grain is the most representative allergen because the target age of our patients belong to a band adult in agreement with what is evident in the literature. Conclusion: In this study, patients with bronchial asthma food allergy are predominantly female. In 43% of cases there was an associated allergic rhinitis in 8% of cases allergic urticaria and in 15% of cases the two coexisting comorbidities.In the group enlisted the history of asthma from food has been confirmed with allergy diagnostic tests at our disposal: the prick test and specific IgE in serum. In our patients the wheat allergen is the most representative because the target age of our patients belong to a band adult in agreement with what is evident in the literature.
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Ferreira, Manuel A. R. "Genetic risk factors for allergic asthma in Australian families /." [St. Lucia, Qld.], 2005. http://www.library.uq.edu.au/pdfserve.php?image=thesisabs/absthe19164.pdf.
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Tabbah, Khaldoun. "Specific immunotherapy for perennial allergic rhinitis." Thesis, University of Southampton, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.299414.
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Masjedi, Khosro. "In vitro analyses of immune responses to metal and organic haptens in humans with contact allergy." Doctoral thesis, Stockholm : Wenner-Gren Institute for Experimental Biology, Stockholm university, 2008. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-7685.
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Devenney, Irene. "Assessing eczema and food allergy in young children." Doctoral thesis, Linköping : Univ, 2006. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-7128.
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Soller, Lianne. "Prevalence and treatment of food allergy in Canada." Thesis, McGill University, 2012. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=106413.
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Recent studies suggest that the prevalence of food allergy is increasing; however, Canadian data on prevalence are sparse. Additionally, although there is unanimous agreement in the medical community that all individuals with a history of food-induced anaphylaxis should have an epinephrine auto-injector (EAI), there is much evidence to suggest that this is not the reality. Using a cross-sectional, randomized telephone survey of Canadian households, we sought to estimate the prevalence of food allergy in Canada and the proportion of allergic Canadians with the EAI, and to determine whether certain characteristics were associated with having the EAI. Of the 10,596 households contacted, 3,666 responded (34.6%), of which 3,613 households, representing 9,667 individuals, provided enough information to be included in the prevalence calculations. The prevalence of self-reported allergy to any food was 8.0%. Of those with probable allergy to at least one of peanut, tree nut, fish, shellfish, and sesame (3.21%), only about 50% had the EAI, and males, those who were older, and those who were single were even less likely to have an EAI. This research suggests that food allergy is a significant health problem, affecting 1 out of every 13 Canadians, and many of them are not adequately managed for their condition. These findings support the need for better education of the public and health care professionals regarding the importance of proper diagnosis and follow-up of individuals with food allergy, and the need to prescribe the EAI to all individuals with a history of an allergic reaction.Des études récentes suggèrent que la prévalence des allergies alimentaires augmente; mais, les données canadiennes sur la prévalence sont éparses. En plus, même s'il y a un accord unanime dans la communauté médicale que tous les patients avec une histoire de l'anaphylaxie causée par un aliment devraient avoir un auto-injecteur d'épinephrine (AIÉ), l'ensemble de recherche démontre que cela n'est pas la réalité. En utilisant un sondage téléphonique auprès des canadiens, nous avons estimé la prévalence des allergies alimentaires chez les canadiens et la proportion des canadiens allergiques qui possèdent un AIÉ. De plus, nous avons déterminé s'il y a certaines caractéristiques qui sont associés avec la possession de l'AIÉ chez les individus souffrant d`allergies alimentaires. Des 10,596 maisons contactées, 3,666 ont répondus (34.6%), et 3,613 de ceux-là ont données assez d`information pour être inclus dans les calculs de prévalence, ce qui représente 9,667 individus. La prévalence des allergies alimentaires auto signalée était de 8.0%. Sur tout ceux avec une allergie probable aux arachides, aux noix, au poisson, aux fruits de mer, et/ou au sésame (3.21%), seulement environ 50% avait l'AIÉ, et les hommes, les adultes, et ceux qui vivait seule étaient encore moins susceptibles d'en avoir un. Cette recherche suggère que les allergies alimentaires sont un problème de santé important, qui touche environ un sur treize canadiens, et la plupart d'entre eux ne sont pas gérés de façon adéquate pour leur condition. Ces conclusions appuient la nécessité de l'éducation pour le publique et les professionnels de la santé en ce qui concerne l'importance d'un diagnostique et un suivi approprié pour les gens avec des allergies alimentaires, et la nécessité de préscrire un AIÉ pour chaque patient avec une histoire d'une réaction allergique.
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Temblay, Jeffrey Nann. "The role of dendritic cells in food allergy." Thesis, University of East Anglia, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.502366.
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Type I food allergies are adverse reactions to food, mediated by immunoglobulin E (1gB) antibody, generated by the gut immune system towards food allergens. There is no known therapy at this time. The aim ofmy work was to dissect the role of dendritic cell-T cell interaction in the development of food allergy. Previous work showed that T cell-mediated apoptosis of dendritic cells (DCs) was impaired in a mouse model of food allergy but the biological relevance of this event is undetermined. T cell-mediated apoptosis was investigated in two mouse strains, with C3H1HeJ showing higher degree of susceptibility than Balb/c mice. In parallel, I aimed to compare the susceptibility of intestinal (Peyer's patch)- and systemic (spleen)-derived DC to T cell-mediated apoptosis in physiological condition (i.e non-sensitised). The latter study showed greater susceptibility of gut Peyer's Patch-derived DC (PP-DC) to antigen-specific T cell-mediated cell death (apoptosis) than spleen-derived DC. Also, similar levels of T cell-mediated apoptosis of DC were observed, irrespective of mouse strain, suggesting increased resistance to T cell-mediated apoptosis alone is not sufficient in triggering full 19B-mediated allergic reactions. However, significant alteration was observed in studies of DC capacity to secrete lymphokine Interleukin-12 (IL-12), which promotes T-helper 1 (Thl) responses. Interleukin-4 (IL-4)-mediated production of IL-12 was impaired in PP-DC of sensitised C3H1HeJ mice but not splenic, non-sensitised or in DC derived from Balb/c mice. This event was not dependent on IL-4 receptor availability upon DC but was linked to reciprocal control ofSTAT-6 and STAT-4 pathways leading IL-12 production by DC. My data indicates that the development of food allergy is linked to the simultaneous failure of at least two different immuno-regulatory mechanisms. A possible hypothesis from this suggests that restoring levels ofIL-12 in the gut may be a novel and effective strategy for food allergy therapy.
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Khan, L. "A study of prohapten activation in contact allergy." Thesis, Bucks New University, 1988. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.384188.
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Georgakarakos, N. D. "Epithelial remodelling of the conjunctiva in ocular allergy." Thesis, University College London (University of London), 2014. http://discovery.ucl.ac.uk/1458122/.
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Background: The spectrum of ocular allergy includes reversible conditions (seasonal, perennial and giant papillary conjunctivitis) and irreversible chronic severe forms of disease involving the cornea (vernal and atopic keratoconjunctivitis). Conjunctival remodelling may play a role in the pathogenesis of chronic allergic eye disease (CAED). Based on findings on asthmatic airway epithelia, it is suggested in chronic asthma that activation of the epithelial-mesenchymal trophic unit (EMTU hypothesis) and EGFR may participate in disease development and account for chronicity, severity and poor response to steroid treatment. This thesis investigates the potential application of the EMTU hypothesis to CAED. Aims and Methods: Conjunctival biopsies of healthy subjects, SAC, GPC (controls group) were compared to VKC and AKC (CAED group) and conjunctival tissues of active and treated OCP. Expression of EGFR, TGFa and CD44 was assessed by means of immunohistochemistry. Cells of two human epithelial conjunctival cell lines (IOBA-NHC & CHwK) received single and multiple cytokine treatments (PMA, IL-17A, TNFQ/IL-1β) and secretion of EGFR, VEGF, CD44, TGFa and p21waf of harvested supernatants were assessed by means of ELISA. Statistical analysis was performed using Mann-Whitney test for the immunohistochemistry and t-test for the ELISA results. Results: Immunohistochemistry studies revealed that there was increased expression of all EMTU remodelling markers in the CAED group compared to Controls (p<0.01). OCP conjunctival biopsies showed no expression for EGFR and TGFa. There was increased secretion of the remodelling molecules by both cell lines after single/multiple cytokine treatments. Conclusions: Epithelial conjunctival remodelling may be responsible for disease severity in CAED as shown in chronic asthma. Epithelial cell EGFR-mediated remodelling parallels the observations made in chronic asthmatic epithelia and the results are in agreement with previous studies in biopsies and tears of VKC patients. Finally suggestions for new treatment strategies are proposed to prevent or inhibit disease perpetuation.
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Denson, Marian. "Rational design of immunotherapy to treat fungal allergy." Thesis, University of Manchester, 2013. https://www.research.manchester.ac.uk/portal/en/theses/rational-design-of-immunotherapy-to-treat-fungal-allergy(ff331eb5-0b27-4a41-823f-b767f5273508).html.
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Background: Asthma affects 5.4 million people in the UK. Asthma subgroups are also susceptible to inhalation of fungal spores (Aspergillus fumigatus) and development of pulmonary fungal aspergilloma; presenting a life threatening but poorly understood condition. NHS costs for corticosteroids, bronchodilators and antifungal agents that are only partially effective continue to rise. Allergy immunotherapy development is of great interest as it is specific to the allergen and can harness key adaptive immune T-cells to down-regulate inflammatory responses. Immunotherapy has been used with varying degrees of success for treatment of grass, pollen, venom, cat and dog allergens however to date has not been directed to fungal allergens. The study aims were: 1) to further understand the A. fumigatus allergens and the protein epitopes responsible for generating immune responses. 2) To genotype participating ABPA/SAFS patients to observe any HLA associations. Methods: 37 subjects with fungal sensitivity were recruited to the study which received permission from the local ethics committee (UHSM LREC). Computer bioinformatic predictions using Propred software identified several potential fungal T cell peptide epitopes; of which 8 peptides were soluble and tested in vitro for specific T-cell proliferation responses by flow cytometric analysis. Skin prick tests determined subject responses to fungal allergens including A. fumigatus, and DNA analysis determined subject HLA type. Results: 5 of 8 soluble peptides were Aspergillus fumigatus derived and 3 from Alternaria alternata. All 8 peptides induced higher CD4 proliferative responses in ABPA/SAFS patients, compared to healthy controls from highest significance to lowest as follows: peptide 1.1 > 9.1 > 8.1 > 2.1 > 9.1.1 > 4.1 > 4.1.1 and 10.1.1. 73% subjects elicited skin responses to A. fumigatus. DNA HLA typing identified alleles associated with ABPA/SAFS but not all allele sub types. Discussion: The ABPA/SAFS group consistently raised T-cell responses to fungal peptides compared to controls. This demonstrates peripheral CD4s retain memory for fungal specificity and clearly respond when challenged with fungal epitopes in vitro. This concept underpins the rationale to further characterize the responding CD4 cells and pursuing bioinformatics approaches for immunotherapy investigations for fungal allergy.
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Badin, Sevil. "Genetic epidemiology of allergy to beta-lactam antibiotics." Thesis, King's College London (University of London), 2017. https://kclpure.kcl.ac.uk/portal/en/theses/genetic-epidemiology-of-allergy-to-betalactam-antibiotics(c6571b05-3322-4662-88c4-88b300c96c9d).html.
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Background: Immediate antibiotic allergic response is an important public health problem. Genetic and molecular characterization will improve treatment outcomes for truly allergic patients, and also reduce the use (and risk of evolution of pathogen resistance) of second-line antibiotics given to patients who incorrectly believe themselves to be allergic to first-line antibiotics. Objective: To identify genetic and metabolic factors associated with allergic responses to beta-lactam antibiotics using the TwinsUK cohort and recruited participants from the Guy’s allergy clinic. Methods: The TwinsUK cohort is the largest registry of adult twins in the UK, and the Guy’s allergy clinic is an outsized clinic covering a large area of the UK. The TwinsUK cohort has been extensively molecularly characterized. After characterising the heritability, we conducted the first high-coverage genomewide association study (GWAS) between 211 self-reported cases in the TwinsUK cohort with questionnaire-defined beta-lactam allergic status and over 1000 individuals without self-reported allergic reaction to any substances. Approximately 2.1 million imputed and genotyped single nucleotide polymorphisms were investigated. A second GWAS was conducted on 48 clinically proven cases from the Guy’s Hospital allergy clinic and ~6000 population controls. In addition a metabolome-wide association study (MWAS) was conducted on the same TwinsUK registry individuals, scanning 510 different metabolites. Results: Following refinement of the self-reported beta-lactam allergy phenotype via the application of a more detailed questionnaire, we estimated a heritability of 21%. The heritability estimates provided positive evidence for a genetic component for beta-lactam allergy. A single hit from the TwinsUK GWAS at the MTHFS/BCL2A1 locus was found (p < 5x10-8 ), indicating a provisional “genomewide significant” hit. Results from the TwinsUK MWAS demonstrated that all metabolites responded as a correlated system to the differences among twins in their allergy status. There were also 4 distinct “metabolome-wide significant” hits, of which two corresponded to known metabolites, suggesting that people who had penicillin allergy had less piperine in their system in comparison with our control group and had higher amounts of 4-vinylphenol-sulfate metabolite. Conclusion: This study demonstrated a genetic component to beta-lactam allergy, and in particular provided evidence for a genetic signal at the MTFHS/BCL2A1 locus. Although the MWAS study showed that there was a metabolomic difference between the allergic and non-allergic individuals. These findings may lead to new personalised treatments based on a combination of genotyping and metabolic characterization. The findings of our studies need verification in independent cohorts.