ABSTRACT
BACKGROUND: A preference for type 2 immunity plays a central role in the pathogenesis of atopic dermatitis (AD). Dupilumab, a monoclonal antibody targeting the IL-4α receptor subunit, inhibits IL-4 and IL-13 signaling. These cytokines contribute significantly to IgE class switch recombination in B-cells, critical in atopic diseases. Recent studies indicate IgG+CD23hiIL-4RA+ memory B-cells (MBC2) as IgE-producing B-cell precursors, linked to total IgE serum levels in atopic patients. Total IgE serum levels decreased during dupilumab treatment in previous studies. OBJECTIVE: To assess the effects of dupilumab treatment in comparison to alternative therapies on the frequency of MBC2 and the correlation to total IgE levels in pediatric patients with AD. METHODS: Pediatric patients with AD, participating in an ongoing trial, underwent randomization into three treatment groups: dupilumab (n=12), cyclosporine (n=12), or topical treatment (n=12). Plasma and Peripheral Blood Mononuclear Cells (PBMCs) were collected at baseline (T0) and after 6 months (T6). Flow cytometry was employed for PBMC phenotyping, ELISA was utilized to assess total IgE levels in plasma. For detailed Methods, please see the Methods section in this article's Online Repository at www.jacionline.org RESULTS: Our findings revealed a significant reduction in MBC2 frequency and total IgE levels among patients treated with dupilumab. Additionally, a significant correlation was observed between MBC2s and total IgE levels CONCLUSION: Systemic blocking of the IL-4RA subunit leads to a decrease in circulating MBC2 cells and total IgE in pediatric AD patients. Our findings unveil a novel mechanism through which dupilumab exerts its influence on the atopic signature.
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Exposure to toxic substances, introduced into our daily lives during industrialization and modernization, can disrupt the epithelial barriers in the skin, respiratory, and gastrointestinal systems, leading to microbial dysbiosis and inflammation. Athletes and physically active individuals are at increased risk of exposure to agents that damage the epithelial barriers and microbiome, and their extreme physical exercise exerts stress on many organs, resulting in tissue damage and inflammation. Epithelial barrier-damaging substances include surfactants and enzymes in cleaning products, laundry and dishwasher detergents, chlorine in swimming pools, microplastics, air pollutants such as ozone, particulate matter, and diesel exhaust. Athletes' high-calorie diet often relies on processed foods that may contain food emulsifiers and other additives that may cause epithelial barrier dysfunction and microbial dysbiosis. The type of the material used in the sport equipment and clothing and their extensive exposure may increase the inflammatory effects. Excessive travel-related stress, sleep disturbances and different food and microbe exposure may represent additional factors. Here, we review the detrimental impact of toxic agents on epithelial barriers and microbiome; bring a new perspective on the factors affecting the health and performance of athletes and physically active individuals.
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BACKGROUND: Antigen-specific memory B cells play a key role in the induction of desensitization and remission to food allergens in oral immunotherapy and in the development of natural tolerance (NT). Here, we characterized milk allergen Bos d 9-specific B cells in oral allergen-specific immunotherapy (OIT) and in children spontaneously outgrowing cow's milk allergy (CMA) due to NT. METHODS: Samples from children with CMA who received oral OIT (before, during, and after), children who naturally outgrew CMA (NT), and healthy individuals were received from Stanford biobank. Bos d 9-specific B cells were isolated by flow cytometry and RNA-sequencing was performed. Protein profile of Bos d 9-specific B cells was analyzed by proximity extension assay. RESULTS: Increased frequencies of circulating milk allergen Bos d 9-specific B cells were observed after OIT and NT. Milk-desensitized subjects showed the partial acquisition of phenotypic features of remission, suggesting that desensitization is an earlier stage of remission. Within these most significantly expressed genes, IL10RA and TGFB3 were highly expressed in desensitized OIT patients. In both the remission and desensitized groups, B cell activation-, Breg cells-, BCR-signaling-, and differentiation-related genes were upregulated. In NT, pathways associated with innate immunity characteristics, development of marginal zone B cells, and a more established suppressor function of B cells prevail that may play a role in long-term tolerance. The analyses of immunoglobulin heavy chain genes in specific B cells demonstrated that IgG2 in desensitization, IgG1, IgA1, IgA2, IgG4, and IgD in remission, and IgD in NT were predominating. Secreted proteins from allergen-specific B cells revealed higher levels of regulatory cytokines, IL-10, and TGF-ß after OIT and NT. CONCLUSION: Allergen-specific B cells are essential elements in regulating food allergy towards remission in OIT-received and naturally resolved individuals.
ABSTRACT
Wheezing children infected with rhinovirus (RV) have a markedly increased risk of subsequently developing recurrencies and asthma. No previous studies have assessed the association between cytokine response and the severity of acute illness in the first wheezing episode in children infected with RV. Forty-seven children treated both as inpatients and as outpatients infected with RV only, aged 3-23 months, with severe first wheezing episodes were recruited. During acute illness, peripheral blood mononuclear cells (PBMCs) were isolated and stimulated with anti-CD3/anti-CD28 in vitro. A multiplex ELISA was used to quantitatively identify 56 different cytokines. The mean age of the children was 17 months, 74% were males, 79% were hospitalized, and 33% were sensitized. In adjusted analyses, the inpatient group was characterized by decreased expressions of interferon gamma (IFN-γ), interleukin 10 (IL-10), macrophage inflammatory protein 1 alpha (MIP-1α), RANTES (CCL5), and tumor necrosis factor-alpha (TNF-α) and an increased expression of ENA-78 (CXCL5) compared to the outpatient group. The cytokine response profiles from the PBMCs were different between the inpatient and outpatient groups. Our results support that firmly controlled interplay between pro-inflammatory and anti-inflammatory responses are required during acute viral infection to absolve the initial infection leading, to less severe illness.
Subject(s)
Cytokines , Leukocytes, Mononuclear , Picornaviridae Infections , Respiratory Sounds , Rhinovirus , Humans , Male , Rhinovirus/immunology , Female , Cytokines/metabolism , Infant , Respiratory Sounds/etiology , Picornaviridae Infections/immunology , Picornaviridae Infections/virology , Leukocytes, Mononuclear/immunology , Leukocytes, Mononuclear/metabolism , Leukocytes, Mononuclear/virology , Severity of Illness IndexABSTRACT
PURPOSE OF REVIEW: Modernization and Westernization in industrialized and developing nations is associated with a substantial increase in chronic noncommunicable diseases. This transformation has far-reaching effects on lifestyles, impacting areas such as economics, politics, social life, and culture, all of which, in turn, have diverse influences on public health. Loss of contact with nature, alternations in the microbiota, processed food consumption, exposure to environmental pollutants including chemicals, increased stress and decreased physical activity jointly result in increases in the frequency of inflammatory disorders including allergies and many autoimmune and neuropsychiatric diseases. This review aims to investigate the relationship between Western lifestyle and inflammatory disorders. RECENT FINDINGS: Several hypotheses have been put forth trying to explain the observed increases in these diseases, such as 'Hygiene Hypothesis', 'Old Friends', and 'Biodiversity and Dysbiosis'. The recently introduced 'Epithelial Barrier Theory' incorporates these former hypotheses and suggests that toxic substances in cleaning agents, laundry and dishwasher detergents, shampoos, toothpastes, as well as microplastic, packaged food and air pollution damage the epithelium of our skin, lungs and gastrointestinal system. Epithelial barrier disruption leads to decreased biodiversity of the microbiome and the development of opportunistic pathogen colonization, which upon interaction with the immune system, initiates local and systemic inflammation. Gaining a deeper comprehension of the interplay between the environment, microbiome and the immune system provides the data to assist with legally regulating the usage of toxic substances, to enable nontoxic alternatives and to mitigate these environmental challenges essential for fostering a harmonious and healthy global environment.
Subject(s)
Hypersensitivity , Industrial Development , Life Style , Humans , Hypersensitivity/immunology , Hypersensitivity/etiology , Environmental Exposure/adverse effectsSubject(s)
COVID-19 , Leadership , Patient Care , SARS-CoV-2 , COVID-19/epidemiology , Humans , Pandemics , Periodicals as TopicABSTRACT
To inform the clinical practice guidelines' recommendations developed by the European Academy of Allergy and Clinical Immunology systematic reviews (SR) assessed using GRADE on the impact of environmental tobacco smoke (ETS) and active smoking on the risk of new-onset asthma/recurrent wheezing (RW)/low lung function (LF), and on asthma-related outcomes. Only longitudinal studies were included, almost all on combustion cigarettes, only one assessing e-cigarettes and LF. According to the first SR (67 studies), prenatal ETS increases the risk of RW (moderate certainty evidence) and may increase the risk of new-onset asthma and of low LF (low certainty evidence). Postnatal ETS increases the risk of new-onset asthma and of RW (moderate certainty evidence) and may impact LF (low certainty evidence). Combined in utero and postnatal ETS may increase the risk of new-onset asthma (low certainty evidence) and increases the risk of RW (moderate certainty evidence). According to the second SR (24 studies), ETS increases the risk of severe asthma exacerbations and impairs asthma control and LF (moderate certainty evidence). According to the third SR (25 studies), active smoking increases the risk of severe asthma exacerbations and of suboptimal asthma control (moderate certainty evidence) and may impact asthma-related quality-of-life and LF (low certainty evidence).
ABSTRACT
BACKGROUND: Human bocaviruses (HBoVs) have been demonstrated in respiratory and gastrointestinal infections; however, the immune response to them has not been studied in detail. In this study, we investigated the B cell immune responses to HBoV1 and HBoV2, representing two different species of bocaviruses in humans. METHODS: We analyzed the effects of stimulations with HBoV1 and 2 virus-like particles (VLPs) and of co-stimulation with HBoV1-rhinovirus (RV) on cells of the immune system by flow cytometry, transcriptomics, and luminometric immune assays. RESULTS: Human B cells, and particularly B regulatory cells (Breg cells), showed an increased immune response to HBoV1-VLPs stimulation. These immune responses were also supported by increased IL-1RA and PDL1 expressions in IL-10+ B cells from peripheral blood mononuclear cells (PBMCs) stimulated with HBoV1-VLPs. In addition, increased levels of IL-10 and IL-1RA were determined in the supernatants of PBMCs following HBoV1-VLPs stimulation. HBoV1-VLPs and RV co-stimulation increased the IL-10+ B cell population. Transcriptome analysis by next-generation RNA sequencing showed an increased expression of IL-10 signalling and Breg cell markers in PBMCs stimulated with HBoV1-VLPs. Furthermore, TGF-ß and chemoattractants MIP-1α, MIP-1ß and IP10 protein levels were high in the supernatants of PBMCs stimulated with HBoV1-VLPs. CONCLUSIONS: The findings demonstrate that in Breg cells, IL-10 signalling pathways, and anti-inflammatory activity are induced by HBoV1, which can explain the often mild nature of the disease. In addition, the immune regulatory response induced by HBoV1-VLPs may indicate a potential immunomodulatory role of HBoV1 on the immune system and may represent an immune regulatory strategy.
Subject(s)
B-Lymphocytes , Human bocavirus , Humans , Human bocavirus/immunology , B-Lymphocytes/immunology , B-Lymphocytes/metabolism , Parvoviridae Infections/immunology , Cytokines/metabolism , Interleukin-10/metabolism , Interleukin-10/immunologyABSTRACT
BACKGROUND: p-Phenylenediamine (PPD) is a potent contact allergen found in many hair colour products. However, not all individuals develop allergic contact dermatitis (ACD) although they are regularly exposed to PPD. It is unclear whether these asymptomatic individuals are true non-responders to PPD or whether they mount a response to PPD without showing any symptoms. METHODS: Skin biopsies were collected from 11 asymptomatic hairdressers regularly exposed to PPD and from 10 individuals with known ACD on day 4 after patch testing with 1% PPD in petrolatum and petrolatum exclusively as control. RNA sequencing and confocal microscopy were performed. RESULTS: T cell activation, inflammation and apoptosis pathways were up-regulated by PPD in both asymptomatic and allergic individuals. Compared to asymptomatic individuals with a negative patch test, individuals with a strong reaction to PPD strongly up-regulated both pro- and anti-inflammatory cytokines genes. Interestingly, PPD treatment induced significant up-regulation of several genes for chemokines, classical type 2 dendritic cell markers and regulatory T cell markers in both asymptomatic and allergic individuals. In addition, apoptosis signalling pathway was activated in both non-responders and allergic individuals. CONCLUSION: This study demonstrates that there are no true non-responders to PPD but that the immune response elicited by PPD differs between individuals and can lead to either tolerance, subclinical inflammation or allergy.
Subject(s)
Dermatitis, Allergic Contact , Phenylenediamines , Skin , Humans , Phenylenediamines/pharmacology , Dermatitis, Allergic Contact/immunology , Dermatitis, Allergic Contact/genetics , Skin/immunology , Skin/pathology , Skin/metabolism , Male , Adult , Female , Gene Expression Regulation/drug effects , Immune Tolerance , Cytokines/metabolism , Allergens/immunology , Middle Aged , Hair Dyes/adverse effects , Young Adult , Patch Tests , ApoptosisABSTRACT
The epithelial barrier theory links the recent rise in chronic non-communicable diseases, notably autoimmune and allergic disorders, to environmental agents disrupting the epithelial barrier. Global pollution and environmental toxic agent exposure have worsened over six decades because of uncontrolled growth, modernization, and industrialization, affecting human health. Introducing new chemicals without any reasonable control of their health effects through these years has led to documented adverse effects, especially on the skin and mucosal epithelial barriers. These substances, such as particulate matter, detergents, surfactants, food emulsifiers, micro- and nano-plastics, diesel exhaust, cigarette smoke, and ozone, have been shown to compromise the epithelial barrier integrity. This disruption is linked to the opening of the tight-junction barriers, inflammation, cell death, oxidative stress, and metabolic regulation. Consideration must be given to the interplay of toxic substances, underlying inflammatory diseases, and medications, especially in affected tissues. This review article discusses the detrimental effect of environmental barrier-damaging compounds on human health and involves cellular and molecular mechanisms.
Subject(s)
Particulate Matter , Vehicle Emissions , Humans , Particulate Matter/adverse effects , Vehicle Emissions/toxicity , Tight Junctions , Allergens , Oxidative Stress , Epithelial CellsABSTRACT
BACKGROUND: Epithelial barrier impairment is associated with many skin and mucosal inflammatory disorders. Laundry detergents have been demonstrated to affect epithelial barrier function in vitro using air-liquid interface cultures of human epithelial cells. METHODS: Back skin of C57BL/6 mice was treated with two household laundry detergents at several dilutions. Barrier function was assessed by electric impedance spectroscopy (EIS) and transepidermal water loss (TEWL) measurements after the 4 h of treatments with detergents. RNA sequencing (RNA-seq) and targeted multiplex proteomics analyses in skin biopsy samples were performed. The 6-h treatment effect of laundry detergent and sodium dodecyl sulfate (SDS) was investigated on ex vivo human skin. RESULTS: Detergent-treated skin showed a significant EIS reduction and TEWL increase compared to untreated skin, with a relatively higher sensitivity and dose-response in EIS. The RNA-seq showed the reduction of the expression of several genes essential for skin barrier integrity, such as tight junctions and adherens junction proteins. In contrast, keratinization, lipid metabolic processes, and epidermal cell differentiation were upregulated. Proteomics analysis showed that the detergents treatment generally downregulated cell adhesion-related proteins, such as epithelial cell adhesion molecule and contactin-1, and upregulated proinflammatory proteins, such as interleukin 6 and interleukin 1 beta. Both detergent and SDS led to a significant decrease in EIS values in the ex vivo human skin model. CONCLUSION: The present study demonstrated that laundry detergents and its main component, SDS impaired the epidermal barrier in vivo and ex vivo human skin. Daily detergent exposure may cause skin barrier disruption and may contribute to the development of atopic diseases.
Subject(s)
Detergents , Skin , Humans , Mice , Animals , Detergents/adverse effects , Detergents/chemistry , Detergents/metabolism , Mice, Inbred C57BL , Skin/metabolism , Epidermis/metabolism , Inflammation/metabolismABSTRACT
The importance of allergen immunotherapy (AIT) is multifaceted, encompassing both clinical and quality-of-life improvements and cost-effectiveness in the long term. Key mechanisms of allergen tolerance induced by AIT include changes in memory type allergen-specific T- and B-cell responses towards a regulatory phenotype with decreased Type 2 responses, suppression of allergen-specific IgE and increased IgG1 and IgG4, decreased mast cell and eosinophil numbers in allergic tissues and increased activation thresholds. The potential of novel patient enrolment strategies for AIT is taking into account recent advances in biomarkers discoveries, molecular allergy diagnostics and mobile health applications contributing to a personalized approach enhancement that can increase AIT efficacy and compliance. Artificial intelligence can help manage and interpret complex and heterogeneous data, including big data from omics and non-omics research, potentially predict disease subtypes, identify biomarkers and monitor patient responses to AIT. Novel AIT preparations, such as synthetic compounds, innovative carrier systems and adjuvants, are also of great promise. Advances in clinical trial models, including adaptive, complex and hybrid designs as well as real-world evidence, allow more flexibility and cost reduction. The analyses of AIT cost-effectiveness show a clear long-term advantage compared to pharmacotherapy. Important research questions, such as defining clinical endpoints, biomarkers of patient selection and efficacy, mechanisms and the modulation of the placebo effect and alternatives to conventional field trials, including allergen exposure chamber studies are still to be elucidated. This review demonstrates that AIT is still in its growth phase and shows immense development prospects.
Subject(s)
Artificial Intelligence , Hypersensitivity , Humans , Desensitization, Immunologic , Hypersensitivity/diagnosis , Hypersensitivity/therapy , Allergens , Biomarkers , Immunoglobulin GABSTRACT
Circulating skin-homing cutaneous lymphocyte-associated antigen (CLA)+ T cells constitute a small subset of human memory T cells involved in several aspects of atopic dermatitis: Staphylococcus aureus related mechanisms, the abnormal Th2 immune response, biomarkers, clinical aspects of the patients, pruritus, and the mechanism of action of targeted therapies. Superantigens, IL-13, IL-31, pruritus, CCL17 and early effects on dupilumab-treated patients have in common that they are associated with the CLA+ T cell mechanisms in atopic dermatitis patients. The function of CLA+ T cells corresponds with the role of T cells belonging to the skin-associated lymphoid tissue and could be a reason why they reflect different mechanisms of atopic dermatitis and many other T cell mediated skin diseases. The goal of this review is to gather all this translational information of atopic dermatitis pathology.
Subject(s)
Dermatitis, Atopic , Humans , Memory T Cells , T-Lymphocyte Subsets , Antigens, Differentiation, T-Lymphocyte , Membrane Glycoproteins , Receptors, Lymphocyte Homing , Skin/pathology , Pruritus , Antigens, NeoplasmABSTRACT
While the number and types of indoor air pollutants is rising, much is suspected but little is known about the impact of their potentially synergistic interactions, upon human health. Gases, particulate matter, organic compounds but also allergens and viruses, fall within the 'pollutant' definition. Distinct populations, such as children and allergy and asthma sufferers are highly susceptible, while a low socioeconomic background is a further susceptibility factor; however, no specific guidance is available. We spend most of our time indoors; for children, the school environment is of paramount importance and potentially amenable to intervention. The interactions between some pollutant classes have been studied. However, a lot is missing with respect to understanding interactions between specific pollutants of different classes in terms of concentrations, timing and sequence, to improve targeting and upgrade standards. SynAir-G is a European Commission-funded project aiming to reveal and quantify synergistic interactions between different pollutants affecting health, from mechanisms to real life, focusing on the school setting. It will develop a comprehensive and responsive multipollutant monitoring system, advance environmentally friendly interventions, and disseminate the generated knowledge to relevant stakeholders in accessible and actionable formats. The aim of this article it to put forward the SynAir-G hypothesis, and describe its background and objectives.
Subject(s)
Air Pollutants , Air Pollution, Indoor , Asthma , Environmental Pollutants , Child , Humans , Air Pollution, Indoor/adverse effects , Air Pollutants/adverse effects , Air Pollutants/analysis , Particulate Matter , Asthma/epidemiology , Asthma/etiology , Environmental MonitoringABSTRACT
Allergic diseases are a major public health problem with increasing prevalence. These immune-mediated diseases are characterized by defective epithelial barriers, which are explained by the epithelial barrier theory and continuously emerging evidence. Environmental exposures (exposome) including global warming, changes and loss of biodiversity, pollution, pathogens, allergens and mites, laundry and dishwasher detergents, surfactants, shampoos, body cleaners and household cleaners, microplastics, nanoparticles, toothpaste, enzymes and emulsifiers in processed foods, and dietary habits are responsible for the mucosal and skin barrier disruption. Exposure to barrier-damaging agents causes epithelial cell injury and barrier damage, colonization of opportunistic pathogens, loss of commensal bacteria, decreased microbiota diversity, bacterial translocation, allergic sensitization, and inflammation in the periepithelial area. Here, we review scientific evidence on the environmental components that impact epithelial barriers and microbiome composition and their influence on asthma and allergic diseases. We also discuss the historical overview of allergic diseases and the evolution of the hygiene hypothesis with theoretical evidence.
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BACKGROUND: Rhinovirus (RV)-induced first wheezing episodes in children are associated with a markedly increased risk of asthma. Previous studies have suggested that human bocavirus 1 (HBoV1) may modify RV-induced immune responses in young children. We investigated cytokine profiles of sole RV- and dual RV-HBoV1-induced first wheezing episodes, and their association with severity and prognosis. METHODS: Fifty-two children infected with only RV and nine children infected with dual RV-HBoV1, aged 3-23 months, with severe first wheezing episodes were recruited. At acute illness and 2 weeks later, peripheral blood mononuclear cells were isolated, and stimulated with anti-CD3/anti-CD28 in vitro. Multiplex ELISA was used to quantitatively identify 56 different cytokines at both study points. Patients were prospectively followed for 4 years. RESULTS: The mean age of the children was 14.3 months, and 30% were sensitized. During the acute illness, the adjusted analyses revealed a decrease in the expression of IL-1b, MIP-1b, Regulated upon activation, normal T cell expressed and presumably secreted (CCL5), TNF-a, TARC, and ENA-78 in the RV-HBoV1 group compared with the RV group. In the convalescence phase, the RV-HBoV1 group was characterized by decreased expression of Fractalkine, MCP-3, and IL-8 compared to the RV group. Furthermore, the hospitalization time was associated with the virus group and cytokine response (interaction p < 0.05), signifying that increased levels of epidermal growth factor and MIP-1b were related with a shorter duration of hospitalization in the RV-HBoV1 coinfection group but not in the RV group. CONCLUSIONS: Different cytokine response profiles were detected between the RV and the RV-HBoV1 groups. Our results show the idea that RV-induced immune responses may be suppressed by HBoV1.
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The exponential growth of precision diagnostic tools, including omic technologies, molecular diagnostics, sophisticated genetic and epigenetic editing, imaging and nano-technologies and patient access to extensive health care, has resulted in vast amounts of unbiased data enabling in-depth disease characterization. New disease endotypes have been identified for various allergic diseases and triggered the gradual transition from a disease description focused on symptoms to identifying biomarkers and intricate pathogenetic and metabolic pathways. Consequently, the current disease taxonomy has to be revised for better categorization. This European Academy of Allergy and Clinical Immunology Position Paper responds to this challenge and provides a modern nomenclature for allergic diseases, which respects the earlier classifications back to the early 20th century. Hypersensitivity reactions originally described by Gell and Coombs have been extended into nine different types comprising antibody- (I-III), cell-mediated (IVa-c), tissue-driven mechanisms (V-VI) and direct response to chemicals (VII). Types I-III are linked to classical and newly described clinical conditions. Type IVa-c are specified and detailed according to the current understanding of T1, T2 and T3 responses. Types V-VI involve epithelial barrier defects and metabolic-induced immune dysregulation, while direct cellular and inflammatory responses to chemicals are covered in type VII. It is notable that several combinations of mixed types may appear in the clinical setting. The clinical relevance of the current approach for allergy practice will be conferred in another article that will follow this year, aiming at showing the relevance in clinical practice where various endotypes can overlap and evolve over the lifetime.
Subject(s)
Hypersensitivity , Humans , Hypersensitivity/diagnosis , BiomarkersABSTRACT
This European Academy of Allergy and Clinical Immunology guideline provides recommendations for diagnosing IgE-mediated food allergy and was developed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. Food allergy diagnosis starts with an allergy-focused clinical history followed by tests to determine IgE sensitization, such as serum allergen-specific IgE (sIgE) and skin prick test (SPT), and the basophil activation test (BAT), if available. Evidence for IgE sensitization should be sought for any suspected foods. The diagnosis of allergy to some foods, such as peanut and cashew nut, is well supported by SPT and serum sIgE, whereas there are less data and the performance of these tests is poorer for other foods, such as wheat and soya. The measurement of sIgE to allergen components such as Ara h 2 from peanut, Cor a 14 from hazelnut and Ana o 3 from cashew can be useful to further support the diagnosis, especially in pollen-sensitized individuals. BAT to peanut and sesame can be used additionally. The reference standard for food allergy diagnosis is the oral food challenge (OFC). OFC should be performed in equivocal cases. For practical reasons, open challenges are suitable in most cases. Reassessment of food allergic children with allergy tests and/or OFCs periodically over time will enable reintroduction of food into the diet in the case of spontaneous acquisition of oral tolerance.
Subject(s)
Food Hypersensitivity , Child , Humans , Food Hypersensitivity/diagnosis , Skin Tests , Immunoglobulin E , Allergens , PollenABSTRACT
Since the 1960 s, our health has been compromised by exposure to over 350,000 newly introduced toxic substances, contributing to the current pandemic in allergic, autoimmune and metabolic diseases. The "Epithelial Barrier Theory" postulates that these diseases are exacerbated by persistent periepithelial inflammation (epithelitis) triggered by exposure to a wide range of epithelial barrier-damaging substances as well as genetic susceptibility. The epithelial barrier serves as the body's primary physical, chemical, and immunological barrier against external stimuli. A leaky epithelial barrier facilitates the translocation of the microbiome from the surface of the afflicted tissues to interepithelial and even deeper subepithelial locations. In turn, opportunistic bacterial colonization, microbiota dysbiosis, local inflammation and impaired tissue regeneration and remodelling follow. Migration of inflammatory cells to susceptible tissues contributes to damage and inflammation, initiating and aggravating many chronic inflammatory diseases. The objective of this review is to highlight and evaluate recent studies on epithelial physiology and its role in the pathogenesis of chronic diseases in light of the epithelial barrier theory.
Subject(s)
Hypersensitivity , Metabolic Diseases , Microbiota , Humans , Inflammation , Chronic Disease , DysbiosisABSTRACT
Over the past two decades, significant progress in understanding of the pathogenesis of type 2 chronic inflammatory diseases has enabled the identification of compounds for more than 20 novel targets, which are approved or at various stages of development, finally facilitating a more targeted approach for the treatment of these disorders. Most of these newly identified pathogenic drivers of type 2 inflammation and their corresponding treatments are related to mast cells, eosinophils, T cells, B cells, epithelial cells and sensory nerves. Epithelial barrier defects and dysbiotic microbiomes represent exciting future drug targets for chronic type 2 inflammatory conditions. Here, we review common targets, current treatments and emerging therapies for the treatment of five major type 2 chronic inflammatory diseases - atopic dermatitis, chronic prurigo, chronic urticaria, asthma and chronic rhinosinusitis with nasal polyps - with a high need for targeted therapies. Unmet needs and future directions in the field are discussed.