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An investigation of the impact of sublingual immunotherapy in experimental models of food allergy and anaphylaxisGadkar, Siyon 11 1900 (has links)
Food allergy is a potentially life-threatening disease affecting up to 10% of individuals in Western countries. Clinical reactivity to food allergens is primarily mediated by immunoglobulin (Ig) E, with symptoms ranging from mild urticaria to anaphylaxis. Currently, food allergy remains a disease without a cure. Oral immunotherapy (OIT), which involves consuming small amounts of allergen, remains an experimental treatment in Canada, although has been approved by the Food and Drug Administration (FDA) in the United States for treatment of peanut allergy. While efficacious to induce desensitization, OIT is accompanied by a significant rate of adverse effects. Sublingual immunotherapy (SLIT) is a novel route of treatment for food allergy, where small amounts of allergen are placed under the tongue and held for 2-3 minutes. In contrast to OIT, SLIT offers not only treatment efficacy but also promises an excellent safety profile.
The first objective of this thesis was to first develop a SLIT regimen in murine models of food allergy where sensitization is carried out either epicutaneously or intragastrically. Secondly, we investigated the efficacy of SLIT in modulating the clinical and humoral responses in prophylactic and semi-therapeutic settings. In the prophylactic setting, where SLIT was administered prior to sensitizing allergen exposures, SLIT-treated mice were completely protected from allergic sensitization including absent production of serum ovalbumin-specific IgE. In the semi-therapeutic setting, where SLIT was administered to mice primed to develop food allergy, it produced a partial protection against food-induced clinical reactivity. This was associated with lower levels of IgE production in comparison to non-treated, allergic mice. Together, this work provides both an optimized SLIT protocol, as well as evidence on the efficacy of SLIT in the treatment of food allergy in murine models. These findings will aid future work investigating the cellular and molecular mechanisms underlying SLIT-induced protection. / Thesis / Master of Science (MSc) / Food allergy is a potentially life-threatening disease which is primarily mediated by IgE antibodies. Strict allergen avoidance and use of rescue epinephrine upon accidental allergen exposure remain the standard of care. Oral immunotherapy, where individuals ingest small amounts of allergen, is currently the experimental treatment of reference to induce clinical tolerance; however, it is accompanied by a significant rate of adverse reactions. In contrast, sublingual immunotherapy (SLIT), which is less efficacious, upholds a superior safety profile. The primary objective of this thesis was to investigate the impact of SLIT in inducing clinical and immunological changes in murine models of food allergy. We demonstrated that when administered prophylactically, SLIT prevents mice from undergoing anaphylaxis. When administered to sensitized mice in a pre-allergic state, SLIT was protective against severe clinical reactivity after challenge. In conclusion, the work presented here establishes a useful platform to investigate the mechanisms underlying SLIT-mediated protection.
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Sublingual ImmunotherapyFerrell, Melissa Leann January 2015 (has links)
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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An analysis of factors associated with compliance and dropout of sublingual immunotherapy on Japanese cedar pollinosis patients / スギ花粉症患者における舌下免疫療法の治療コンプライアンスと脱落に関する研究Imanaka, Takahiro 24 September 2019 (has links)
京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第22035号 / 医博第4520号 / 新制||医||1038(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 椛島 健治, 教授 佐藤 俊哉, 教授 福原 俊一 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM
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Eficácia clínica e alterações na resposta de anticorpos sistêmicos e de mucosa após imunoterapia sublingual em crianças alérgicas a ácaros: um estudo randomizado duplo-cego, controlado com placeboQueirós, Meimei Guimarães Junqueira de 19 August 2011 (has links)
This study aimed to evaluate the clinical efficacy and systemic/mucosal antibody
response changes after sublingual immunotherapy (SLIT) using Dermatophagoides
pteronyssinus (Dpt) allergens with or without bacterial extracts in mite-allergic
children. One-hundred and two patients presenting allergic rhinitis with or without
asthma were selected for a randomized double-blind, placebo-controlled trial and
distributed into three groups: DPT (Dpt allergen extract, n=34), DPT+MRB (Dpt
allergen plus mixed respiratory bacterial extracts, n=36), and Placebo (n=32). Clinical
evaluation and immunological analyses were carried out before and after 12 and 18
months of treatment, including rhinitis/asthma symptom and medication scores, skin
prick test (SPT) to Dpt extract, and measurements of Dpt, Der p 1, Der p 2 specific
IgE, IgG4, and IgG1 in serum and specific IgA in saliva and nasal lavage fluid.
Clinical results showed a significant decline in rhinitis/asthma symptom scores in all
groups, but medication use decreased only in DPT group after 12 months. SPT
results showed no significant changes and SLIT was generally safe, with no severe
systemic reactions. SLIT using Dpt allergen alone induced increased serum IgG4
levels to Dpt, Der p 1 and Der p 2, and increased serum IgG1 and salivary IgA levels
to Dpt and Der p 1. SLIT using DPT+MRB was able to decrease IgE levels to Der p
2, to increase salivary IgA levels to Der p 1, but had no changes on specific IgG4 and
IgG1 levels. In conclusion, clinical improvement was observed both in the SLIT
group and the control, but only active SLIT was able to modulate the
mucosal/systemic antibody responses. These findings support the role of specific
serum IgG4 and IgG1, in addition to salivary IgA, as probable blocking antibodies or
biomarkers of tolerance that may be useful for monitoring the allergen specific
immunotherapy. / Este estudo teve como objetivo avaliar a eficácia clínica e alterações da resposta de
anticorpos sistêmicos e de mucosa após a imunoterapia sublingual (SLIT), utilizando
alérgenos de Dermatophagoides pteronyssinus (Dpt), com ou sem extratos
bacterianos em crianças alérgicas a ácaros. Cento e dois pacientes com rinite
alérgica com ou sem asma foram selecionados para um estudo randomizado duplocego,
controlado por placebo e distribuídos em três grupos: DPT (extrato alergênico
de Dpt, n=34), DPT+MRB (extrato alergênico de Dpt associado com extrato de
bactérias mistas do trato respiratório, n=36), e Placebo (n=32). Avaliação clínica e
análises imunológicas foram realizadas antes do tratamento e após 12 e 18 meses,
incluindo a pontuação de escores de sintomas e medicamentos de rinite/asma, teste
cutâneo (SPT) ao extrato Dpt, e medidas de anticorpos específicos IgE, IgG4 e IgG1
para Dpt, Der p 1, Der p 2 no soro e IgA específicos na saliva e no lavado nasal. Os
resultados clínicos mostraram uma redução significativa nos escores de sintomas de
rinite/asma em todos os grupos, mas o uso de medicamentos diminuiu apenas no
grupo DPT após 12 meses. Resultados de SPT não mostraram mudanças
significativas e SLIT foi geralmente segura, sem reação sistêmica grave. SLIT
usando somente alérgeno Dpt induziu aumento dos níveis de IgG4 para Dpt, Der p 1
e Der p 2 no soro, e aumentou os níveis de IgG1 no soro e salivares de IgA para Dpt
e Der p 1. SLIT usando DPT+MRB foi capaz de diminuir os níveis de IgE para Der p
2, aumentar os níveis salivares de IgA para Der p 1, mas não tiveram alterações nos
níveis de anticorpos específicos de IgG4 e IgG1. Em conclusão, foi observado
melhora clínica tanto no grupo da SLIT como do controle, porém somente na SLIT
com alérgeno foi capaz de modular as respostas de anticorpos sistêmicos e de
mucosa. Estes achados reforçam o papel de anticorpos IgG4 e IgG1 séricos
específicos, além de IgA salivar, como prováveis anticorpos bloqueadores ou
biomarcadores de tolerância que podem ser úteis para monitoramento da
imunoterapia alérgeno-específica. / Doutor em Imunologia e Parasitologia Aplicadas
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Tropomiosina de barata Periplaneta americana: papel na imunoterapia sublingual em modelo experimental de hiper-responsividade brônquica e na investigação da resposta IgE em pacientes com dermatite atópica / Tropomyosin of cockroach Periplaneta americana: role in sublingual immunotherapy in an experimental model of bronchial hyperresponsiveness and in the investigation of IgE response in patients with atopic dermatitisMaia, Amanda Rodrigues 28 May 2019 (has links)
A prevalência de doenças alérgicas incluindo asma e dermatite atópica aumentou nos últimos anos. A asma é uma doença crônica caracterizada por hiper-responsividade das vias aéreas e limitação variável ao fluxo aéreo, reversível espontaneamente ou com tratamento. A elevada prevalência, mortalidade e custos associados tornam a doença um importante problema de saúde pública que requer atenção. A dermatite atópica (DA) é uma doença inflamatória crônica da pele, caracterizada por prurido intenso, eritema, escoriações, liquenificação na pele entre outras características. A DA causa profundo impacto na vida do indivíduo e da família e geralmente mostra os primeiros sintomas durante a infância. Ambas as doenças podem ser associadas a sensibilização a alérgenos. Nosso grupo mostrou que entre pacientes com rinite e/ou asma alérgicos a barata a tropomiosina da barata Periplaneta americana é um alérgeno principal. Em invertebrados, a tropomiosina induz resposta IgE e reatividade cruzada entre invertebrados incluindo ácaros, barata, camarão e parasitas. No presente estudo, produzimos tropomiosina recombinante de barata (alérgeno Per a 7) com elevado grau de pureza e com quantidades mínimas de endotoxina. Em modelo experimental de asma em camundongos, com sensibilização e desencadeamento com Per a 7 recombinante, houve aumento do número de células totais, e de eosinófilos, neutrófilos e linfócitos no lavado broncoalveolar. Alérgeno Per a 7 recombinante foi também utilizado em ELISA quimérico para investigar a resposta IgE a este alérgeno em 112 pacientes com dermatite atópica. A idade dos pacientes variou de 3 a 67 anos com média de 24,9 (± 15,4) anos, com 75 indivíduos do sexo feminino (67%). Nos 112 pacientes, o SCORAD apresentou média de 43,1 (± 18,1) e foram relatadas asma e rinite em 42 e 85 indivíduos, respectivamente. Níveis de IgE total apresentaram ampla variação, de 14,2 a 63.000 UI/mL, com média geométrica de 2.193 UI/mL. A idade de início dos sintomas e o tempo de doença apresentaram médias, respectivamente, de 9,5 (± 12,9) e 15,4 (± 12,3) anos. Trinta pacientes (26,8%) apresentaram níveis detectáveis de IgE para Per a 7 recombinante, com variação de 2,3 a 3.191 UI/mL. A razão de IgE específica para Per a7/IgE total nestes pacientes variou de 0,03% a 33,8%. Dividindo os pacientes em sensibilizados e não sensibilizados ao alérgeno de barata, observamos que não houve diferença significante entre os grupos com relação à idade de início dos sintomas, tempo de doença, SCORAD, presença de rinite ou asma e níveis de IgE total. Nossos resultados mostraram que o alérgeno Per a 7 recombinante induziu resposta inflamatória com caraterísticas semelhante à observada em humanos, em modelo experimental de asma em camundongos. Frequência menor de reatividade IgE ao alérgeno Per a 7 foi observada entre pacientes com dermatite atópica em nosso meio, quando comparada à observada previamente em pacientes com asma e/ou rinite. Não houve associação entre a presença de sensibilização IgE ao alérgeno Per a 7 e a gravidade da dermatite atópica, presença de asma ou rinite, idade de início e tempo de doença, e níveis de IgE total. Entretanto, a investigação do perfil de sensibilização IgE tem importância ao se considerar o uso de imunoterapia alérgenoespecífica em pacientes com dermatite atópica. / The prevalence of allergic diseases has increased in recent years, including asthma and atopic dermatitis. Asthma is a chronic disease resulting from airway hyperresponsiveness and variable airflow limitation, reversible spontaneously or with treatment. The high prevalence, mortality, and associated costs make the disease an important public health problem which requires attention. Atopic dermatitis (AD) is a chronic inflammatory skin disease, as asthma has high prevalence, and it is characterized by intense itching, erythema, excoriations, lichenification in the skin among other characteristics. The AD causes profound impact on individual and family´s life and usually shows the first symptoms during childhood. Both diseases could be related and associated with sensitization to allergens. In the case of asthma, allergy to cockroach is well known to be related with the disease. In 1999, a Brazilian study in our group has shown that among patients with allergic rhinitis and /or asthma the tropomyosin of the American cockroach Periplaneta americana (Per a 7) is a major allergen. This protein is present in vertebrates and invertebrates, and was related to induction of IgE response and cross-reactivity against among invertebrates, including mites, cockroaches, shrimp and parasites. In the present study, we produced recombinant tropomyosin from cockroach (Per a 7 allergen) with high purity and minimal amounts of endotoxin. In an experimental model of asthma in mice, with sensitization and triggering with recombinant Per a 7, there was an increase in the number of total cells, and eosinophils, neutrophils and lymphocytes in the bronchoalveolar lavage. Per a 7 allergen was also used in chimeric ELISA to investigate IgE response to this allergen in 112 patients with atopic dermatitis. Patients\' ages ranged from 3 to 67 years, mean of 24.9 (± 15.4) years, 75 female subjects (67%). In the 112 patients, a mean of SCORAD presented 43.1 (± 18.1) and asthma and rhinitis were reported in 42 and 85 individuals, respectively. Total IgE levels varied from 14.2 to 63.000 IU / mL, with a geometric mean of 2,193 IU / mL. The age at onset of symptoms and disease time presented averages, respectively, of 9.5 (± 12.9) and 15.4 (± 12.3) years. Thirty patients (26.8%) had detectable IgE recombinant Per a 7 levels, ranging from 2.3 to 3191 IU / mL. The ratio of IgA specific for Per a7 / total IgE in these patients ranged from 0.03% to 33.8%. Dividing the patients into sensitized and not sensitized to the cockroach allergen, we observed that there was no significant difference between the groups regarding the age of onset of symptoms, disease time, SCORAD, presence of rhinitis or asthma, and total IgE levels. Our results showed that recombinant Per a 7 allergen induced an inflammatory response with characteristics similar to that observed in humans in an experimental model of asthma in mice. Minor frequency reactivity of IgE Per a 7 allergen was observed among patients with atopic dermatitis in our group, when compared to that previously observed in patients with asthma and / or rhinitis. There was no association between the presence of IgE sensitization to the Per 7 allergen and the severity of atopic dermatitis, presence of asthma or rhinitis, age at onset and disease time, and total IgE levels. However, the investigation of the IgE sensitization profile is important when considering the use of allergen-specific immunotherapy in patients with atopic dermatitis
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