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1.
Allergy ; 79(4): 977-989, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38433402

RESUMO

BACKGROUND: IgE-mediated food allergy (FA) is a global health concern with substantial individual and societal implications. While diverse intervention strategies have been researched, inconsistencies in reported outcomes limit evaluations of FA treatments. To streamline evaluations and promote consistent reporting, the Core Outcome Measures for Food Allergy (COMFA) initiative aimed to establish a Core Outcome Set (COS) for FA clinical trials and observational studies of interventions. METHODS: The project involved a review of published clinical trials, trial protocols and qualitative literature. Outcomes found as a result of review were categorized and classified, informing a two-round online-modified Delphi process followed by hybrid consensus meeting to finalize the COS. RESULTS: The literature review, taxonomy mapping and iterative discussions with diverse COMFA group yielded an initial list of 39 outcomes. The iterative online and in-person meetings reduced the list to 13 outcomes for voting in the formal Delphi process. One more outcome was added based on participant suggestions after the first Delphi round. A total of 778 participants from 52 countries participated, with 442 participating in both Delphi rounds. No outcome met a priori criteria for inclusion, and one was excluded as a result of the Delphi. Thirteen outcomes were brought to the hybrid consensus meeting as a result of Delphi and two outcomes, 'allergic symptoms' and 'quality of life' achieved consensus for inclusion as 'core' outcomes. CONCLUSION: In addition to the mandatory reporting of adverse events for FA clinical trials or observational studies of interventions, allergic symptoms and quality of life should be measured as core outcomes. Future work by COMFA will define how best to measure these core outcomes.


Assuntos
Hipersensibilidade Alimentar , Qualidade de Vida , Humanos , Técnica Delphi , Hipersensibilidade Alimentar/diagnóstico , Hipersensibilidade Alimentar/terapia , Imunoglobulina E , Avaliação de Resultados em Cuidados de Saúde , Projetos de Pesquisa , Resultado do Tratamento , Ensaios Clínicos como Assunto , Estudos Observacionais como Assunto
2.
Int Arch Allergy Immunol ; 185(1): 56-62, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37729879

RESUMO

INTRODUCTION: Skin tests are one of the most widely used diagnostic tools for suspected drug allergies in children. Studies on systemic reactions occurring during skin testing with allergens have mostly been conducted in pediatric and adult patient groups together. However, data on adverse reactions including allergic reactions after drug skin tests in children are scarce. It is aimed to determine the adverse reactions after skin test in children with suspected drug allergy. METHODS: Patients who underwent a drug skin test due to the suspicion of drug allergy between May 2017 and June 2020 were evaluated, retrospectively. Data about adverse reactions seen after skin testing at the testing area in the clinic were analyzed. RESULTS: The study included 1,073 children (585 [54.5%] boys and 488 [45.5%] girls) with a median age of 7.5 years. A total of 12 (1.1%) reactions were detected after skin testing, and 4 (0.4%) of them were allergic reactions. Of the allergic reactions, three were anaphylaxis and one was urticaria. Two of the reactions (1 anaphylaxis and 1 urticaria) were detected after the skin prick test and the remaining 2 were detected after intradermal test. Three of the nonallergic reactions were considered as vasovagal reactions and seven were considered as nonspecific and anxiety-related reactions. CONCLUSION: Although drug skin tests were generally well-tolerated and adverse reactions were rare, severe allergic reactions including anaphylaxis may ensue. Skin tests should be necessarily performed in clinical settings in experienced centers.


Assuntos
Anafilaxia , Hipersensibilidade a Drogas , Urticária , Masculino , Adulto , Feminino , Humanos , Criança , Anafilaxia/diagnóstico , Anafilaxia/etiologia , Estudos Retrospectivos , Testes Cutâneos , Hipersensibilidade a Drogas/diagnóstico , Hipersensibilidade a Drogas/etiologia , Urticária/diagnóstico , Urticária/etiologia
3.
Ann Allergy Asthma Immunol ; 131(6): 703-712, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37619777

RESUMO

The epithelial barrier represents the point of contact between the host and the external environment. It is the first line of defense against external insults in the skin and in the gastrointestinal and upper and lower respiratory tracts. The steep increase in chronic disorders in recent decades, including allergies and autoimmune disorders, has prompted studies to investigate the immune mechanisms of their underlying pathogeneses, all of which point to a thought-provoking shared finding: disrupted epithelial barriers. Climate change with global warming has increased the frequency of unpredictable extreme weather events, such as wildfires, droughts, floods, and aberrant and longer pollination seasons, among many others. These increasingly frequent natural disasters can synergistically damage the epithelial barrier integrity in the presence of environmental pollution. A disrupted epithelial barrier induces proinflammatory activation of epithelial cells and alarmin production, namely, epithelitis. The "opened" epithelial barrier facilitates the entry of the external exposome into and underneath the epithelium, triggering an expulsion response driven by inflammatory cells in the area and chronic inflammation. These changes are associated with microbial dysbiosis with colonizing opportunistic pathogens and decreased commensals. These cellular and molecular events are key mechanisms in the pathogenesis of numerous chronic inflammatory disorders. This review summarizes the impact of global warming on epithelial barrier functions in the context of allergic diseases. Further studies in the impact of climate change on the dysfunction of the epithelial barriers are warranted to improve our understanding of epithelial barrier-related diseases and raise awareness of the environmental insults that pose a threat to our health.


Assuntos
Aquecimento Global , Hipersensibilidade , Humanos , Epitélio , Inflamação , Células Epiteliais
4.
Asia Pac Allergy ; 13(1): 28-39, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37389096

RESUMO

It is now longer than half a century, humans, animals, and nature of the world are under the influence of exposure to many newly introduced noxious substances. These exposures are nowadays pushing the borders to be considered as the causative or exacerbating factors for many chronic disorders including allergic, autoimmune/inflammatory, and metabolic diseases. The epithelial linings serve as the outermost body's primary physical, chemical, and immunological barriers against external stimuli. The "epithelial barrier theory" hypothesizes that these diseases are aggravated by an ongoing periepithelial inflammation triggered by exposure to a wide range of epithelial barrier-damaging insults that lead to "epithelitis" and the release of alarmins. A leaky epithelial barrier enables the microbiome's translocation from the periphery to interepithelial and even deeper subepithelial areas together with allergens, toxins, and pollutants. Thereafter, microbial dysbiosis, characterized by colonization of opportunistic pathogen bacteria and loss of the number and biodiversity of commensal bacteria take place. Local inflammation, impaired tissue regeneration, and remodeling characterize the disease. The infiltration of inflammatory cells to affected tissues shows an effort to expulse the tissue invading bacteria, allergens, toxins, and pollutants away from the deep tissues to the surface, representing the "expulsion response." Cells that migrate to other organs from the inflammatory foci may play roles in the exacerbation of various inflammatory diseases in distant organs. The purpose of this review is to highlight and appraise recent opinions and findings on epithelial physiology and its role in the pathogenesis of chronic diseases in view of the epithelial barrier theory.

5.
Front Allergy ; 3: 887672, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35873598

RESUMO

Introduction: In the last decades, we have seen a rapid increase in the prevalence of allergic diseases such as asthma, allergic rhinitis, atopic dermatitis, and food allergies. The environmental changes caused by industrialization, urbanization and modernization, including dramatic increases in air pollutants such as particulate matter (PM), diesel exhaust, nitrogen dioxide (NO2), ozone (O3), alarming effects of global warming, change and loss of biodiversity, affect both human health and the entire ecosystem. Objective: In this review, we aimed to discuss the effects of the external exposome on epithelial barriers and its relationship with the development of allergic diseases by considering the changes in all stakeholders of the outer exposome together, in the light of the recently proposed epithelial barrier hypothesis. Method: To reach current, prominent, and comprehensive studies on the subject, PubMed databases were searched. We included the more resounding articles with reliable and strong results. Results: Exposure to altered environmental factors such as increased pollution, microplastics, nanoparticles, tobacco smoke, food emulsifiers, detergents, and household cleaners, and climate change, loss and change in microbial biodiversity, modifications in the consumption of dietary fatty acids, the use of emulsifiers, preservatives and the decrease in the antioxidant content of the widely consumed western diet may disrupt the epithelial barriers of the skin, respiratory and gastrointestinal tracts, making us more vulnerable to exogeneous allergens and microbes. Epithelial cell activation, microbial dysbiosis and bacterial translocation disrupt the immune balance and a chronic Th2 inflammation ensues. Conclusion: Dramatic increases in air pollution, worrisome effects of global warming, dysbiosis, changing dietary habits and the complex interactions of all these factors affect the epithelial barriers and local and systemic inflammation. We want to draw attention to the emerging health effects of environmental changes and to motivate the public to influence government policies for the well-being of humans and the nature of the earth and the well-being of future generations.

6.
Allergy ; 77(5): 1418-1449, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35108405

RESUMO

Environmental exposure plays a major role in the development of allergic diseases. The exposome can be classified into internal (e.g., aging, hormones, and metabolic processes), specific external (e.g., chemical pollutants or lifestyle factors), and general external (e.g., broader socioeconomic and psychological contexts) domains, all of which are interrelated. All the factors we are exposed to, from the moment of conception to death, are part of the external exposome. Several hundreds of thousands of new chemicals have been introduced in modern life without our having a full understanding of their toxic health effects and ways to mitigate these effects. Climate change, air pollution, microplastics, tobacco smoke, changes and loss of biodiversity, alterations in dietary habits, and the microbiome due to modernization, urbanization, and globalization constitute our surrounding environment and external exposome. Some of these factors disrupt the epithelial barriers of the skin and mucosal surfaces, and these disruptions have been linked in the last few decades to the increasing prevalence and severity of allergic and inflammatory diseases such as atopic dermatitis, food allergy, allergic rhinitis, chronic rhinosinusitis, eosinophilic esophagitis, and asthma. The epithelial barrier hypothesis provides a mechanistic explanation of how these factors can explain the rapid increase in allergic and autoimmune diseases. In this review, we discuss factors affecting the planet's health in the context of the 'epithelial barrier hypothesis,' including climate change, pollution, changes and loss of biodiversity, and emphasize the changes in the external exposome in the last few decades and their effects on allergic diseases. In addition, the roles of increased dietary fatty acid consumption and environmental substances (detergents, airborne pollen, ozone, microplastics, nanoparticles, and tobacco) affecting epithelial barriers are discussed. Considering the emerging data from recent studies, we suggest stringent governmental regulations, global policy adjustments, patient education, and the establishment of individualized control measures to mitigate environmental threats and decrease allergic disease.


Assuntos
Expossoma , Hipersensibilidade Alimentar , Microbiota , Exposição Ambiental/efeitos adversos , Hipersensibilidade Alimentar/epidemiologia , Humanos , Microplásticos , Plásticos
7.
Allergy Asthma Proc ; 42(5): e135-e144, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34474716

RESUMO

Background: Several factors that increase the risk of severe food-induced anaphylaxis have been identified. Objective: We aimed to determine the demographic, etiologic, and clinical features of food-induced anaphylaxis in early childhood and also any other factors associated with severe anaphylaxis. Methods: We carried out a medical chart review of anaphylaxis cases from 16 pediatric allergy and immunology centers in Turkey. Results: The data of 227 patients with 266 food-induced anaphylaxis episodes were included in the study. The median (interquartile range) age of the first anaphylaxis episode was 9 months (6-18 months); 160 of these patients were boys (70.5%). The anaphylaxis episodes were mild in 75 cases (28.2%), moderate in 154 cases (57.9%), and severe in 37 cases (13.9%). The most frequent food allergens involved were cow's milk (47.4%), nuts (16.7%), and hen's egg (15.8%). Epinephrine was administered in only 98 (36.8%) of these anaphylaxis episodes. A logistic regression analysis revealed two statistically significant factors that were independently associated with severe anaphylaxis: the presence of angioedema and hoarseness during the anaphylactic episode. Urticaria was observed less frequently in patients who developed hypotension. In addition, confusion and syncope were associated with 25.9- and 44.6-fold increases, respectively, in the risk of concomitant hypotension. Conclusion: Cow's milk, nuts, and hen's egg caused the majority of mild and moderate-to-severe anaphylaxis episodes. The presence of angioedema and hoarseness in any patient who presents with a history of food-induced anaphylaxis should alert clinicians that the reaction may be severe. In addition, the presence of confusion, syncope, or stridor probably indicates concomitant hypotension.


Assuntos
Anafilaxia , Angioedema , Hipersensibilidade Alimentar , Hipotensão , Hipersensibilidade a Leite , Alérgenos , Anafilaxia/diagnóstico , Anafilaxia/epidemiologia , Anafilaxia/etiologia , Animais , Bovinos , Hipersensibilidade a Ovo , Feminino , Hipersensibilidade Alimentar/complicações , Hipersensibilidade Alimentar/diagnóstico , Hipersensibilidade Alimentar/epidemiologia , Rouquidão , Humanos , Lactente , Masculino , Hipersensibilidade a Leite/complicações , Hipersensibilidade a Leite/diagnóstico , Hipersensibilidade a Leite/epidemiologia , Hipersensibilidade a Noz , Síncope , Turquia
8.
Pediatr Allergy Immunol ; 32(8): 1781-1787, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34181779

RESUMO

BACKGROUND: Clarithromycin hypersensitivity is reported as the most common cause of non-ß-lactam antibiotic allergy in children. Clarithromycin is frequently prescribed in cases of suspected ß-lactam hypersensitivity. Oral provocation tests stand as the gold standard to confirm drug hypersensitivity as diagnostic value of skin tests is variable. We analyzed the frequency of true clarithromycin hypersensitivity ratio and its relationship with ß-lactam allergy among children with suspected clarithromycin hypersensitivity and evaluated the diagnostic value of skin tests. METHODS: The study included 160 children referred with suspected clarithromycin hypersensitivity. Clinical history and allergy workups including skin tests or/and oral provocation tests were retrieved from medical records. RESULTS: Oral provocation test confirmed clarithromycin hypersensitivity rate was 5.6% (n = 9/160). Skin tests with clarithromycin showed positivity in 32.6% (n = 29/89) of the tested patients. The sensitivity of clarithromycin skin tests was negligible, and specificity was 73.9% (95% confidence interval [CI], 64.7-81.8). Eighty-eight of the patients (55%) reported that they had previously tolerated a ß-lactam antibiotic. ß-lactam hypersensitivity was suspected in 40% (n = 64/160) of the patients (simultaneous [n = 10], sequential [n = 19], distant form [n = 35]) in relation with clarithromycin usage. ß-lactam hypersensitivity (95% CI, 2.1-70.6, p = .005) and sequential usage of clarithromycin after the development of a rash with amoxicillin-clavulanic acid (95% CI, 2.0-96.4, p = .007) were found as risk factors for confirmed clarithromycin hypersensitivity. CONCLUSION: The frequency of confirmed clarithromycin hypersensitivity was found low among suspected patients. Oral provocation test is crucial for definite diagnosis. Confirmed ß-lactam allergy may be attributed as a risk factor for clarithromycin hypersensitivity, particularly clarithromycin treatment after a developing rash with amoxicillin-clavulanic acid in sequential usage.


Assuntos
Claritromicina , Hipersensibilidade a Drogas , Antibacterianos/efeitos adversos , Criança , Claritromicina/efeitos adversos , Hipersensibilidade a Drogas/diagnóstico , Hipersensibilidade a Drogas/epidemiologia , Humanos , Testes Cutâneos , beta-Lactamas/efeitos adversos
9.
Pediatr Allergy Immunol ; 32(5): 963-970, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33604910

RESUMO

BACKGROUND: Lockdown was imposed for children for 75 days in Turkey to limit the spread of COVID-19. During this period, children have to stay indoors, which might probably increase their exposures to indoor allergens and pollutants. Besides, reduced exposures to respiratory tract infections and outdoor pollutants might be favorable outcomes of this lockdown period. We evaluated the effects of the lockdown on house dust mite (HDM)-sensitized children with respiratory allergies. METHODS: Three-month clinical and medication data of 165 mild-moderate asthmatic children with or without allergic rhinitis (AR), who were grouped according to their HDM sensitization status, were retrieved from patient records. Demographics, asthma control tests, nasal visual analog scores, and outdoor air quality monitoring data were used for assessments in comparisons with the same period in the previous year. RESULTS: Eighty-four patients had asthma, and 81 patients had asthma with AR. Sensitization to HDM was present in 61.8% of the children. Patients experienced reduced numbers of upper respiratory tract infections (P = .008) and reduced asthma exacerbations (P < .001) compared with the same period in the previous year. Asthma control tests were significantly improved (P < .001), and cumulative inhaled corticosteroid usages were significantly reduced (P < .001). Noteworthily, nasal symptoms were significantly worsened in HDM-sensitized asthmatics with AR (P < .001). CONCLUSIONS: This study highlighted that reduction in respiratory tract infections and outdoor pollution may play roles in asthma control and prevent exacerbations despite continuous indoor allergen exposure. Besides, worsening of nasal symptoms in HDM-sensitized asthmatics with AR implies the importance of indoor avoidance measures for AR control.


Assuntos
Antígenos de Dermatophagoides , Asma , Controle de Doenças Transmissíveis , Alérgenos , Animais , Asma/prevenção & controle , COVID-19/prevenção & controle , Criança , Poeira , Humanos , Pyroglyphidae/imunologia , Turquia
10.
Int Arch Allergy Immunol ; 182(7): 607-614, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33601370

RESUMO

BACKGROUND: Urticaria can be the only sign of a food allergy or can be seen together with other signs and symptoms of a food allergy. OBJECTIVE: To determine the demographic, etiologic, and clinical features of food-induced acute urticaria in childhood. METHODS: Patients suspected of food-induced acute urticaria were included in this prospective cross-sectional multicenter study. RESULTS: Two hundred twenty-nine urticaria cases were included in this study. Seventeen patients who did not meet the inclusion criteria of the study were excluded. Of the 212 included cases, 179 (84.4%) were diagnosed with definitive food-induced acute urticaria. The most common foods causing acute urticaria were cow's milk, hen's eggs, and nuts in 56.4, 35.2, and 19% of cases, respectively. The positive predictive value of a history of milk-induced acute urticaria together with a milk-specific IgE >5 kU/L for cow's milk-induced acute urticaria was 92% (95% CI: 81-96%). A history of cow's milk-induced and/or hen's egg-induced acute urticaria was consistent with a definitive diagnosis of food-induced urticaria (Chen's kappa: 0.664 and 0.627 for milk and eggs, respectively). Urticaria activity scores were higher in patients with food-induced acute urticaria (p = 0.002). CONCLUSION: Cow's milk, hen's eggs, and nuts were the most common allergens in the etiology of childhood food-induced acute urticaria. Although the urticaria activity score provides guidance for diagnosis, an oral food challenge is often essential for the definitive diagnosis of a patient with a history of food-induced acute urticaria.


Assuntos
Alérgenos/imunologia , Hipersensibilidade Alimentar/complicações , Hipersensibilidade Alimentar/imunologia , Alimentos/efeitos adversos , Urticária/diagnóstico , Urticária/etiologia , Pré-Escolar , Estudos Transversais , Diagnóstico Diferencial , Feminino , Hipersensibilidade Alimentar/diagnóstico , Humanos , Masculino , Prognóstico , Avaliação de Sintomas
11.
Pediatr Allergy Immunol ; 32(1): 177-185, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32786099

RESUMO

BACKGROUND: Paracetamol, a non-steroidal anti-inflammatory drug, is commonly being used for fever and pain relief worldwide. The aim of this study was to evaluate children with a suspected history of paracetamol hypersensitivity. METHODS: Sixty patients who were referred to our clinic in between January 2015 and December 2018 with a suspected history of paracetamol hypersensitivity were included. Reactions were classified according to the European Network for Drug Allergy (ENDA)/Global Allergy and Asthma European Network classification and European Academy of Allergy and Clinical Immunology (EAACI)/ENDA Position Paper. Diagnoses were confirmed by skin tests and oral challenge tests (OCTs). In those with verified paracetamol hypersensitivity, an OCT with a strong COX-1 inhibitor was performed to classify the type of the reaction to refer as either selective or cross-intolerance hypersensitivity. A subsequent OCT with a selective COX-2 inhibitor was performed in those cross-intolerant patients to find out a safe alternative drug. RESULTS: Sixty OCTs with paracetamol were performed to patients with a median age of 8.5 years, and hypersensitivity to paracetamol was verified in 8 patients. Four children were classified as selective responders, and 3 were classified as cross-intolerant after OCT with a COX-1 inhibitor. Overall, skin test positivity for paracetamol was detected in only one patient, in whom OCT with paracetamol was negative. In all 3 cross-intolerant patients, a safe alternative non-steroidal anti-inflammatory drug was identified after an OCT with a selective COX-2 inhibitor. CONCLUSION: OCT stands as the gold-standard procedure in verifying the diagnosis of patients with paracetamol-induced drug hypersensitivity, as well as, in defining the type of reactions and finding out safe alternative drugs.


Assuntos
Acetaminofen , Hipersensibilidade a Drogas , Acetaminofen/efeitos adversos , Anti-Inflamatórios não Esteroides/efeitos adversos , Criança , Hipersensibilidade a Drogas/diagnóstico , Humanos , Testes Cutâneos
13.
Front Immunol ; 11: 568598, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33224138

RESUMO

IgE-mediated food allergies are caused by adverse immunologic responses to food proteins. Allergic reactions may present locally in different tissues such as skin, gastrointestinal and respiratory tract and may result is systemic life-threatening reactions. During the last decades, the prevalence of food allergies has significantly increased throughout the world, and considerable efforts have been made to develop curative therapies. Food allergen immunotherapy is a promising therapeutic approach for food allergies that is based on the administration of increasing doses of culprit food extracts, or purified, and sometime modified food allergens. Different routes of administration for food allergen immunotherapy including oral, sublingual, epicutaneous and subcutaneous regimens are being evaluated. Although a wealth of data from clinical food allergen immunotherapy trials has been obtained, a lack of consistency in assessed clinical and immunological outcome measures presents a major hurdle for evaluating these new treatments. Coordinated efforts are needed to establish standardized outcome measures to be applied in food allergy immunotherapy studies, allowing for better harmonization of data and setting the standards for the future research. Several immunological parameters have been measured in food allergen immunotherapy, including allergen-specific immunoglobulin levels, basophil activation, cytokines, and other soluble biomarkers, T cell and B cell responses and skin prick tests. In this review we discuss different immunological parameters and assess their applicability as potential outcome measures for food allergen immunotherapy that may be included in such a standardized set of outcome measures.


Assuntos
Dessensibilização Imunológica , Hipersensibilidade Alimentar/terapia , Animais , Antialérgicos/uso terapêutico , Citocinas/imunologia , Hipersensibilidade Alimentar/imunologia , Humanos , Imunidade Humoral , Imunoglobulina E/imunologia , Omalizumab/uso terapêutico , Linfócitos T/imunologia
14.
Acta Med Acad ; 49(2): 164-180, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33189122

RESUMO

This review mainly focuses on the mechanisms of peripheral immune tolerance within the perspectives of innate immunity. Healthy immune response requires balanced interaction of the highly specialized elements of immunity within a harmony. Innate immunity supported by microbial pattern recognition receptors, physical anatomical barriers and soluble effectors stands as the first line of defense against non-self-antigens. Innate receptors recognize major classes of pathogens and trigger immediate immune/inflammatory responses. The decisive action has been the key issue in skewing of immune reactivity to a pathogen or to tolerate self- and non-self-antigens. Non-responsiveness to self- or to harmless foreign antigens with means of multiple mechanisms is known as immune tolerance; a non-inflammatory, non-proliferative and suppressive response linked to suppressor molecules as CTLA-4 and cytokines like IL-10, TGF-ß and IL-35, and also to non-inflammatory blocking antibody isotypes as IgG4. Regulatory cells ascertain both induction and maintenance of peripheral tolerance. Allergic diseases, autoimmunity and transplant rejection are the best illustrations of immune tolerance loss. Adaptive immunity responsible for both establishment and maintenance of a long-lasting immune responsiveness is mainly fine-tuned by actions of innate immunity. Better understanding of the relationship between innate immunity and immune tolerance is a prerequisite both for better understanding of pathogenesis of tolerance-related diseases and also for development of novel therapeutic options. CONCLUSION: Recent evidences point the important roles of innate immunity for establishment of immune tolerance with decisive role in central mechanisms. In a peremptory way, a 'balanced tolerance' is essential for the survival.


Assuntos
Autoimunidade/imunologia , Hipersensibilidade/imunologia , Tolerância Imunológica/imunologia , Imunidade Inata/imunologia , Imunidade Adaptativa/imunologia , Rejeição de Enxerto/imunologia , Humanos , Tolerância a Antígenos Próprios/imunologia
15.
Allergol Int ; 69(4): 549-560, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32900655

RESUMO

Allergen-specific immunotherapy (AIT) is the mainstay treatment for the cure of allergic disorders, with depicted efficacy and safety by several trials and meta-analysis. AIT impressively contributes to the management of allergic rhinitis, asthma and venom allergies. Food allergy is a new arena for AIT with promising results, especially via novel administration routes. Cell subsets with regulatory capacities are induced during AIT. IL-10 and transforming growth factor (TGF)-ß are the main suppressor cytokines, in addition to surface molecules such as cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) and programmed cell death protein-1 (PD-1) within the micro milieu. Modified T- and B-cell responses and antibody isotypes, increased activity thresholds for eosinophils, basophils and mast cells and consequent limitation of inflammatory cascades altogether induce and maintain a state of sustained allergen-specific unresponsiveness. Established tolerance is reflected into the clinical perspectives as improvement of allergy symptoms together with reduced medication requirements and evolved disease severity. Long treatment durations, costs, reduced patient compliance and risk of severe, even life-threatening adverse reactions during treatment stand as major limiting factors for AIT. By development of purified non-allergenic, highly-immunogenic modified allergen extracts, and combinational usage of them with novel adjuvant molecules via new routes may shorten treatment durations and possibly reduce these drawbacks. AIT is the best model for custom-tailored therapy of allergic disorders. Better characterization of disease endotypes, definition of specific biomarkers for diagnosis and therapy follow-up, as well as precision medicine approaches may further contribute to success of AIT in management of allergic disorders.


Assuntos
Dessensibilização Imunológica , Hipersensibilidade/terapia , Alérgenos/imunologia , Animais , Humanos , Tolerância Imunológica , Inflamação/terapia
16.
Allergy ; 75(10): 2445-2476, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32584441

RESUMO

With the worldwide spread of the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) resulting in declaration of a pandemic by the World Health Organization (WHO) on March 11, 2020, the SARS-CoV-2-induced coronavirus disease-19 (COVID-19) has become one of the main challenges of our times. The high infection rate and the severe disease course led to major safety and social restriction measures worldwide. There is an urgent need of unbiased expert knowledge guiding the development of efficient treatment and prevention strategies. This report summarizes current immunological data on mechanisms associated with the SARS-CoV-2 infection and COVID-19 development and progression to the most severe forms. We characterize the differences between adequate innate and adaptive immune response in mild disease and the deep immune dysfunction in the severe multiorgan disease. The similarities of the human immune response to SARS-CoV-2 and the SARS-CoV and MERS-CoV are underlined. We also summarize known and potential SARS-CoV-2 receptors on epithelial barriers, immune cells, endothelium and clinically involved organs such as lung, gut, kidney, cardiovascular, and neuronal system. Finally, we discuss the known and potential mechanisms underlying the involvement of comorbidities, gender, and age in development of COVID-19. Consequently, we highlight the knowledge gaps and urgent research requirements to provide a quick roadmap for ongoing and needed COVID-19 studies.


Assuntos
Betacoronavirus/imunologia , Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/imunologia , Pneumonia Viral/diagnóstico , Pneumonia Viral/imunologia , Academias e Institutos , COVID-19 , Teste para COVID-19 , Infecções por Coronavirus/patologia , Humanos , Pandemias , Pneumonia Viral/patologia , SARS-CoV-2
17.
Pediatr Allergy Immunol ; 31 Suppl 25: 1-101, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32436290

RESUMO

Allergen immunotherapy is a cornerstone in the treatment of allergic children. The clinical efficiency relies on a well-defined immunologic mechanism promoting regulatory T cells and downplaying the immune response induced by allergens. Clinical indications have been well documented for respiratory allergy in the presence of rhinitis and/or allergic asthma, to pollens and dust mites. Patients who have had an anaphylactic reaction to hymenoptera venom are also good candidates for allergen immunotherapy. Administration of allergen is currently mostly either by subcutaneous injections or by sublingual administration. Both methods have been extensively studied and have pros and cons. Specifically in children, the choice of the method of administration according to the patient's profile is important. Although allergen immunotherapy is widely used, there is a need for improvement. More particularly, biomarkers for prediction of the success of the treatments are needed. The strength and efficiency of the immune response may also be boosted by the use of better adjuvants. Finally, novel formulations might be more efficient and might improve the patient's adherence to the treatment. This user's guide reviews current knowledge and aims to provide clinical guidance to healthcare professionals taking care of children undergoing allergen immunotherapy.


Assuntos
Dessensibilização Imunológica/métodos , Hipersensibilidade/terapia , Pediatria/normas , Guias de Prática Clínica como Assunto , Administração Sublingual , Adolescente , Alérgenos/imunologia , Animais , Asma/imunologia , Asma/terapia , Biomarcadores/análise , Criança , Pré-Escolar , Dessensibilização Imunológica/normas , Pessoal de Saúde , Humanos , Hipersensibilidade/imunologia , Hipersensibilidade/prevenção & controle , Injeções Subcutâneas , Pólen/imunologia , Pyroglyphidae/imunologia , Linfócitos T Reguladores/imunologia
20.
Allergy ; 74(11): 2064-2076, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31070805

RESUMO

The European Academy of Allergy and Clinical Immunology (EAACI) organized the first European Strategic Forum on Allergic Diseases and Asthma. The main aim was to bring together all relevant stakeholders and decision-makers in the field of allergy, asthma and clinical Immunology around an open debate on contemporary challenges and potential solutions for the next decade. The Strategic Forum was an upscaling of the EAACI White Paper aiming to integrate the Academy's output with the perspective offered by EAACI's partners. This collaboration is fundamental for adapting and integrating allergy and asthma care into the context of real-world problems. The Strategic Forum on Allergic Diseases brought together all partners who have the drive and the influence to make positive change: national and international societies, patients' organizations, regulatory bodies and industry representatives. An open debate with a special focus on drug development and biomedical engineering, big data and information technology and allergic diseases and asthma in the context of environmental health concluded that connecting science with the transformation of care and a joint agreement between all partners on priorities and needs are essential to ensure a better management of allergic diseases and asthma in the advent of precision medicine together with global access to innovative and affordable diagnostics and therapeutics.


Assuntos
Asma/epidemiologia , Financiamento de Capital , Hipersensibilidade/epidemiologia , Pesquisa , Pesquisa Translacional Biomédica , Asma/diagnóstico , Asma/terapia , Big Data , Bioengenharia , Gerenciamento Clínico , Desenvolvimento de Medicamentos , Saúde Ambiental , Europa (Continente)/epidemiologia , Política de Saúde , Humanos , Hipersensibilidade/diagnóstico , Hipersensibilidade/etiologia , Hipersensibilidade/terapia , Ciência da Implementação , Tecnologia da Informação , Participação do Paciente , Pesquisa Translacional Biomédica/economia , Pesquisa Translacional Biomédica/legislação & jurisprudência , Pesquisa Translacional Biomédica/métodos , Pesquisa Translacional Biomédica/organização & administração
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