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Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can result in a prolonged multisystem disorder termed long COVID, which may affect up to 10% of people following coronavirus disease 2019 (COVID-19). It is currently unclear why certain individuals do not fully recover following SARS-CoV-2 infection. Summary: In this review, we examine immunological mechanisms that may underpin the pathophysiology of long COVID. These mechanisms include an inappropriate immune response to acute SARS-CoV-2 infection, immune cell exhaustion, immune cell metabolic reprogramming, a persistent SARS-CoV-2 reservoir, reactivation of other viruses, inflammatory responses impacting the central nervous system, autoimmunity, microbiome dysbiosis, and dietary factors. Key Messages: Unfortunately, the currently available diagnostic and treatment options for long COVID are inadequate, and more clinical trials are needed that match experimental interventions to underlying immunological mechanisms. [ABSTRACT FROM AUTHOR]

Allergic diseases of the (upper and lower) airways, the skin and the gastrointestinal tract, are on the rise, resulting in impaired quality of life, decreased productivity, and increased healthcare costs. As allergic diseases are mostly tissue‐specific, local sampling methods for respective biomarkers offer the potential for increased sensitivity and specificity. Additionally, local sampling using noninvasive or minimally invasive methods can be cost‐effective and well tolerated, which may even be suitable for primary or home care sampling. Non‐ or minimally invasive local sampling and diagnostics may enable a more thorough endotyping, may help to avoid under‐ or overdiagnosis, and may provide the possibility to approach precision prevention, due to early diagnosis of these local diseases even before they get systemically manifested and detectable. At the same time, dried blood samples may help to facilitate minimal‐invasive primary or home care sampling for classical systemic diagnostic approaches. This EAACI position paper contains a thorough review of the various technologies in allergy diagnosis available on the market, which analytes or biomarkers are employed, and which samples or matrices can be used. Based on this assessment, EAACI position is to drive these developments to efficiently identify allergy and possibly later also viral epidemics and take advantage of comprehensive knowledge to initiate preventions and treatments. [ABSTRACT FROM AUTHOR]

Biologicals have transformed the way of treatment of many immune-mediated disorders including cancer, autoimmune, and allergic diseases.[[1]] Biologicals and the understanding of their impact on diseases is a rapidly evolving field in which emerging important questions arise. Therefore, current EAACI AIT guidelines for HDM-driven allergic asthma do not recommend co-administration of biologicals with HDM AIT.[5] Large clinical trials with other biologicals are currently under development. EAACI Guidelines on biologicals will be of great relevance to move forward and consolidate the concept of personalized medicine and precision health for allergic diseases and asthma. [Extracted from the article]

The microbiota can play important roles in the development of human immunity and the establishment of immune homeostasis. Lifestyle factors including diet, hygiene, and exposure to viruses or bacteria, and medical interventions with antibiotics or anti‐ulcer medications, regulate phylogenetic variability and the quality of cross talk between innate and adaptive immune cells via mucosal and skin epithelia. More recently, microbiota and their composition have been linked to protective effects for health. Imbalance, however, has been linked to immune‐related diseases such as allergy and cancer, characterized by impaired, or exaggerated immune tolerance, respectively. In this AllergoOncology position paper, we focus on the increasing evidence defining the microbiota composition as a key determinant of immunity and immune tolerance, linked to the risk for the development of allergic and malignant diseases. We discuss novel insights into the role of microbiota in disease and patient responses to treatments in cancer and in allergy. These may highlight opportunities to improve patient outcomes with medical interventions supported through a restored microbiome. [ABSTRACT FROM AUTHOR]

Epidemiologic studies report an increase in food allergies in industrialized countries, but mainly focus on children and young adults. This leads to the impression that food allergies do not occur in the older population. However, age-related changes dramatically affect both the innate as well as the adaptive immune system - a phenomenon known as immunosenescence. Deficiencies in micronutrients, especially zinc and iron, as well as vitamin D, in the elderly may also contribute to the development of allergies. A further risk factor of the elderly in developing food allergies could also be the decreased digestive ability of the stomach due to atrophic gastritis or anti-ulcer medication. In these settings, undigested proteins may persist and become allergenic. In fact, mouse models indicate that these pharmaceuticals support the induction of Th2 responses not only in young adult, but also in aged animals. Previous reports have already suggested that allergies are underdiagnosed among the elderly. Based on our own recent study conducted in a geriatric nursing home, we also suggest that food allergies may be underestimated. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Nitration of proteins on tyrosine residues, which can occur due to polluted air under "summer smog" conditions, has been shown to increase the allergic potential of allergens. Since nitration of tyrosine residues is also observed during inflammatory responses, this modification could directly influence protein immunogenicity and might therefore contribute to food allergy induction. In the current study we have analyzed the impact of protein nitration on sensitization via the oral route. Methodology/Principal Findings: BALB/c mice were immunized intragastrically by feeding untreated ovalbumin (OVA), sham-nitrated ovalbumin (snOVA) or nitrated ovalbumin (nOVA) with or without concomitant acid-suppression. To analyze the impact of the sensitization route, the allergens were also injected intraperitoneally. Animals being fed OVA or snOVA under acid-suppressive medication developed significantly elevated levels of IgE, and increased titers of specific IgG1 and IgG2a antibodies. Interestingly, oral immunizations of nOVA under anti-acid treatment did not result in IgG and IgE formation. In contrast, intraperitoneal immunization induced high levels of OVA specific IgE, which were significantly increased in the group that received nOVA by injection. Furthermore, nOVA triggered significantly enhanced mediator release from RBL cells passively sensitized with sera from allergic mice. Gastric digestion experiments demonstrated protein nitration to interfere with protein stability as nOVA was easily degraded, whereas OVA and snOVA remained stable up to 120 min. Additionally, HPLC-chip-MS/MS analysis showed that one tyrosine residue (Y107) being very efficiently nitrated is part of an ovalbumin epitope recognized exclusively after oral sensitization. Conclusions/Significance: These data indicated that despite the enhanced triggering capacity in existing allergy, nitration of OVA may be associated with a reduced de novo sensitizing capability via the oral route due to enhanced protein digestibility and/or changes in antibody epitopes. [ABSTRACT FROM AUTHOR]

Background: IgE antibodies play a paramount role in the pathogenesis of various intestinal disorders. To gain insights in IgE-mediated pathophysiology of the gut, we investigated the expression of the high affinity IgE receptor FcϵRI in human intestinal epithelium. Methodology/Principal Findings: FcϵRI α-chain, as detected by immunohistochemistry, was positive in epithelial cells for eight of eleven (8/11) specimens from colon cancer patients and 5/11 patients with inflammation of the enteric mucosa. The FceRIa positive epithelial cells co-expressed FcϵRIγ, whereas with one exception, none of the samples was positive for the β-chain in the epithelial layer. The functionality of FcϵRI was confirmed in situ by human IgE binding. In experiments with human intestinal tumor cell lines, subconfluent Caco-2/TC7 and HCT-8 cells were found to express the α- and γ-chains of FcϵRI and to bind IgE, whereas confluent cells were negative for c-chains. Conclusions/Significance: Our data provide the first evidence that the components of a functional FceRI are in vitro expressed by the human intestinal epithelial cells depending on differentiation and, more importantly, in situ in epithelia of patients with colon cancer or gastrointestinal inflammations. Thus, a contribution of FceRI either to immunosurveillance or pathophysiology of the intestinal epithelium is suggested. [ABSTRACT FROM AUTHOR]

Abstract: Based on two clinical observations of adverse reactions during exercise with latex sport bands, we aimed to assess the possible risk for allergic patients posed by this equipment by investigating allergen content and IgE binding potential. Protein extracts of three different latex sport bands were characterized with sera of latex allergic patients. The IgE recognition profile of the allergic patients was identified by component resolved diagnosis and the allergen composition of the extracts was characterized by inhibition assays with the recombinant latex allergens Hev b 1, 3, 5, 6.02, and 8. The sera showed pronounced IgE binding to all three blotted extracts, however with diverse patterns. Inhibition assays revealed the presence of Hev b 1, 3, 5, and 8 in latex sport band extracts. The clinical relevance of contained allergens was demonstrated by strong skin reactions when testing with latex sport bands. From our results we conclude that latex sport bands contain clinically relevant allergens and may cause latex allergic individuals to experience allergic symptoms, potentially amplified by exercise-induced mechanisms. Even though latex is labeled on products, it is important that patients as well as athletic trainers and physical therapists recognize the risk of adverse reactions with these bands. [Copyright &y& Elsevier]

Abstract: The gastrointestinal tract represents the biggest immune organ of the human body and has 3 distinct functions: (1) barrier and defense against potential pathogens, (2) ignorance or tolerance of innocuous agents, and (3) digestion and nutritional uptake of alimentary compounds. Recent studies have indicated that especially structural features of dietary proteins seem to be a precondition for the induction of immediate type immune responses. Crystallographic studies of allergen molecules have been fundamental for epitope studies in a 3-dimensional format using peptides or mimotopes. The identified IgE epitopes were all conformational and responsible for high-affinity interactions with specific IgE. Moreover, numerous studies have indicated that allergens, among them food allergens, preferentially form di-, tri-, or multimers, thus leading to a repetitive display of epitopes. As B-lymphocytes are pattern recognizers, this feature is essential for a memory response, but may also be critical for the very first allergen contact and initiation of the IgE response. Here we review the key candidate cells in the gut, which are capable of recognizing conformation and molecular patterns, but may also be involved in skewing the immune response towards Th2. Animal models have been basic for understanding the molecular principles of food allergy and they will be increasingly indispensable for the definition of novel vaccination strategies. Therefore, the available models are critically analyzed in this review. [Copyright &y& Elsevier]

Abstract: Parvalbumin, the major fish allergen, is recognized by allergen-specific IgE of more than 90% of all fish-allergic patients. A detailed knowledge of allergenic structures is crucial for developing a vaccine inducing blocking antibodies specifically directed towards the IgE binding epitopes. In the present study we aimed to use the phage display technique to generate mimotopes, which mimic epitopes on parvalbumin. Parvalbumin-specific IgE was purified from sera of fish-allergic patients and used for screening of a constrained decamer phage library. After four rounds of biopanning using parvalbumin-specific IgE, five phage clones were selected which were specifically recognized by parvalbumin-specific IgE as well as IgG. DNA sequencing and peptide alignment revealed a high degree of sequence similarities between the mimotopes. Interestingly, on the surface of natural parvalbumin three regions could be defined by computational mimotope matching. In accordance, previously defined allergenic peptides of cod parvalbumin highlighted areas in close proximity or overlapping with the mimotope matching sites. From the presented data we conclude that our approach identified conformational epitopes of parvalbumin relevant for IgE and IgG binding. We suggest that these mimotopes are suitable candidates for an epitope-specific immunotherapy of fish-allergic patients. [Copyright &y& Elsevier]

The latest outbreak of a coronavirus disease in 2019 (COVID‐19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), evolved into a worldwide pandemic with massive effects on health, quality of life, and economy. Given the short period of time since the outbreak, there are several knowledge gaps on the comparative and zoonotic aspects of this new virus. Within the One Health concept, the current EAACI position paper dwells into the current knowledge on SARS‐CoV‐2's receptors, symptoms, transmission routes for human and animals living in close vicinity to each other, usefulness of animal models to study this disease and management options to avoid intra‐ and interspecies transmission. Similar pandemics might appear unexpectedly and more frequently in the near future due to climate change, consumption of exotic foods and drinks, globe‐trotter travel possibilities, the growing world population, the decreasing production space, declining room for wildlife and free‐ranging animals, and the changed lifestyle including living very close to animals. Therefore, both the society and the health authorities need to be aware and well prepared for similar future situations, and research needs to focus on prevention and fast development of treatment options (medications, vaccines). [ABSTRACT FROM AUTHOR]

Presents a study on the ability of anti-ulcer drugs to promote immunoglobulin (IgE) formation toward dietary antigens in adult patients. Therapy that resulted in an increase in food-specific IgE in 25 percent of all treated patients; Experiments used to predict the allergenicity of food antigens through their resistance to gastric digestion; Foods in which the most resistant proteins were found.

Introduction: Guidelines recommend treating asthma exacerbations (AAEs) with bronchodilators combined with inhaled and/or systemic corticosteroids. Indications for antibiotic prescriptions for AAEs are usually not incorporated although the literature shows antibiotics are frequently prescribed. Aim: To investigate the antibiotic prescription rates in AAEs and explore the possible determining factors of those practices. Methods: A digital survey was created to determine the antibiotic prescription rates in AAEs and the influencing factors for the prescription practices. The survey was distributed among European academy of allergy and clinical immunology (EAACI) members by mass emailing and through regional/national societies in the Netherlands, Italy, Greece, and Poland. Furthermore, we retrieved local antibiotic prescription rates. Results: In total, 252 participants completed the survey. Respondents stated that there is a lack of guidelines to prescribe antibiotics in AAEs. The median antibiotic prescription rate in this study was 19% [IQR: 0%–40%] and was significantly different between 4 professions: paediatrics 0% [IQR: 0%–37%], pulmonologists 25% [IQR: 10%–50%], general practitioners 25% [IQR: 0%–50%], and allergologists 17% [IQR: 0%–33%]) (p = 0.046). Additional diagnostic tests were performed in 71.4% of patients before prescription and the most common antibiotic classes prescribed were macrolides (46.0%) and penicillin (42.9%). Important clinical factors for health care providers to prescribe antibiotics were colorised/purulent sputum, abnormal lung sounds during auscultation, fever, and presence of comorbidities. Conclusion: In 19% of patients with AAEs, antibiotics were prescribed in various classes with a broad range among different subspecialities. This study stresses the urgency to compose evidence‐based guidelines to aim for more rational antibiotic prescriptions for AAE. [ABSTRACT FROM AUTHOR]

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex disease characterized by profound fatigue, post-exertional malaise (PEM), and neurocognitive dysfunction. Immune dysregulation and gastrointestinal symptoms are commonly observed in ME/CFS patients. Despite affecting approximately 0.89% of the general population, the underlying pathophysiological mechanisms remain poorly understood. This study aimed to elucidate the relationship between immunological characteristics and intestinal barrier function in ME/CFS patients. ME/CFS patients were stratified into two groups based on their immune competence. After documentation of detailed medical records, serum and plasma samples were collected for the assessment of inflammatory immune mediators and biomarkers for intestinal barrier integrity by ELISA. We found reduced complement protein C4a levels in immunodeficient ME/CFS patients suggesting a subgroup-specific innate immune dysregulation. ME/CFS patients without immunodeficiencies exhibit a mucosal barrier leakage, as indicated by elevated levels of Lipopolysaccharide-binding protein (LBP). Stratifying ME/CFS patients based on immune competence enabled the distinction of two subgroups with different pathophysiological patterns. The study highlights the importance of emphasizing precise patient stratification in ME/CFS, particularly in the context of defining suitable treatment strategies. Given the substantial health and socioeconomic burden associated with ME/CFS, urgent attention and research efforts are needed to define causative treatment approaches. [ABSTRACT FROM AUTHOR]

Over the past years, eosinophils have become a focus of scientific interest, especially in the context of their recently uncovered functions (e.g. antiviral, anti‐inflammatory, regulatory). These versatile cells display both beneficial and detrimental activities under various physiological and pathological conditions. Eosinophils are involved in the pathogenesis of many diseases which can be classified into primary (clonal) and secondary (reactive) disorders and idiopathic (hyper)eosinophilic syndromes. Depending on the biological specimen, the eosinophil count in different body compartments may serve as a biomarker reflecting the underlying pathophysiology and/or activity of distinct diseases and as a therapy‐driving (predictive) and monitoring tool. Personalized selection of an appropriate therapeutic strategy directly or indirectly targeting the increased number and/or activity of eosinophils should be based on the understanding of eosinophil homeostasis including their interactions with other immune and non‐immune cells within different body compartments. Hence, restoring as well as maintaining homeostasis within an individual's eosinophil pool is a goal of both specific and non‐specific eosinophil‐targeting therapies. Despite the overall favourable safety profile of the currently available anti‐eosinophil biologics, the effect of eosinophil depletion should be monitored from the perspective of possible unwanted consequences. [ABSTRACT FROM AUTHOR]

Keywords: circadian rhythm; food allergy; intermittent fasting; intestinal barrier function; oral tolerance EN circadian rhythm food allergy intermittent fasting intestinal barrier function oral tolerance 2931 2933 3 09/03/21 20210901 NES 210901 Abbreviations IF intermittent fasting MHC major histocompatibility complex SI small intestine SIEC small intestinal epithelial cells Intestinal immune homeostasis and well-balanced oral tolerance mechanisms are essential for defending the host against pathogens and toxic substances while simultaneously absorbing essential nutrients to nourish the human body. Moreover, increasing evidence shows that food allergy development is strongly associated with a dysfunctional gastrointestinal barrier.1 In several studies, an impaired allergen digestion induced by, for example, administration of gastric acid-suppressive medication, enhanced susceptibility to food allergy development. [Extracted from the article]

For proteins to cause IgE-mediated allergic reactions, several common characteristics have to be defined, including small molecular size, solubility and stability to changing pH levels and enzymatic degradation. Nevertheless, these features are not unique for potent allergens, but are also observed in non-allergenic proteins. Due to the increasing awareness by regulatory authorities regarding the allergy pandemic, definition of characteristics unique to potent allergens would facilitate allergenicity assessment in the future. Despite major research efforts even to date the features unique for major allergens have not been elucidated so far. The route of allergen entry into the organism determines to a great extent these required characteristics. Especially orally ingested allergens are exposed to the harsh milieu of the gastrointestinal tract but might additionally be influenced by food processing. Depending on molecular properties such as disulphide bonds contributing to protein fold and formation of conformational IgE epitopes, posttranslational protein modification or protein food matrix interactions, enzymatic and thermal stability might differ between allergens. Moreover, also ligand binding influences structural stability. In the current review article, we aim at highlighting specific characteristics and molecular pattern contributing to a stabilized protein structure and overall allergenicity. [ABSTRACT FROM AUTHOR]

Abstract: According to the state of the art two classes of food allergens exist: class 1 allergens are capable to sensitize as well as to trigger allergic reactions via the oral route. In contrast, class 2 food allergens do not sensitize orally because they are easily digested and thereby lose their sensitization potential. For the same reason, they trigger IgE mediated reactions only at the primary contact sites. However, our animal and human studies demonstrated that also class 2 food allergens may acquire allergenic potential when gastric digestion is hampered, e.g. by hypoacidity. Therefore, in vitro digestion tests used as decision criteria by international food safety authorities are suitable tools for revealing class 1 food allergens, but they do not permit a safety classification of digestion-labile class 2 proteins in settings of stomach insufficiency. [Copyright &y& Elsevier]

In humans, manifestations of allergic gastrointestinal reactions cannot easily he visualized and assessed due to the inaccessibility of the target organ. Therefore, most of the pathophysiological information derives from animal studies. The authors reported recently that specific IgE, mucosal and skin hypersensitivity were induced in BALB/c mice, when food proteins were given orally under concomitant suppression of gastric acid by proton pump inhibitors, H2-blockers, or acid neutralizers. By downregulating the proton concentration in the gastric fluids, these drugs prevented peptic digestion.

Microbial metabolism of specific dietary components, such as fiber, contributes to the sophisticated inter‐kingdom dialogue in the gut that maintains a stable environment with important beneficial physiological, metabolic, and immunological effects on the host. Historical changes in fiber intake may be contributing to the increase of allergic and hypersensitivity disorders as fiber‐derived metabolites are evolutionarily hardwired into the molecular circuitry governing immune cell decision‐making processes. In this review, we highlight the importance of fiber as a dietary ingredient, its effects on the microbiome, its effects on immune regulation, the importance of appropriate timing of intervention to target any potential window of opportunity, and potential mechanisms for dietary fibers in the prevention and management of allergic diseases. In addition, we review the human studies examining fiber or prebiotic interventions on asthma and respiratory outcomes, allergic rhinitis, atopic dermatitis, and overall risk of atopic disorders. While exposures, interventions, and outcomes were too heterogeneous for meta‐analysis, there is significant potential for using fiber in targeted manipulations of the gut microbiome and its metabolic functions in promoting immune health. [ABSTRACT FROM AUTHOR]

By the April 12, 2022, the COVID‐19 pandemic had resulted in over half a billion people being infected worldwide. There have been 6.1 million deaths directly due to the infection, but the pandemic has had many more short‐ and long‐term pervasive effects on the physical and mental health of the population. Allergic diseases are among the most prevalent noncommunicable chronic diseases in the pediatric population, and health‐care professionals and researchers were seeking answers since the beginning of pandemic. Children are at lower risk of developing severe COVID‐19 or dying from infection. Allergic diseases are not associated with a higher COVID‐19 severity and mortality, apart from severe/poorly controlled asthma. The pandemic disrupted routine health care, but many mitigation strategies, including but not limited to telemedicine, were successfully implemented to continue delivery of high‐standard care. Although children faced a multitude of pandemic‐related issues, allergic conditions were effectively treated remotely while reduction in air pollution and lack of contact with outdoor allergens resulted in improvement, particularly respiratory allergies. There is no evidence to recommend substantial changes to usual management modalities of allergic conditions in children, including allergen immunotherapy and use of biologicals. Allergic children are not at greater risk of multisystem inflammatory syndrome development, but some associations with Long COVID were reported, although the data are limited, and further research is needed. This statement of the EAACI Section on Pediatrics provides recommendations based on the lessons learnt from the pandemic, as available evidence. [ABSTRACT FROM AUTHOR]

Background: Diagnosis of food allergies is challenging, as combining information from specific IgE (sIgE)‐sensitization pattern and skin prick tests (SPTs) with clinical history is necessary for a personalized management of allergic patients. The aim of this study was to compare two molecular tests, the ImmunoCAP ISAC (ISAC) and the Allergy Explorer, version 2 (ALEX2) in the context of pollen food syndrome (PFS) diagnosis in a real‐life scenario, to assess the benefit of multiplex testing in PFS patients. Methods: Diagnosis of food allergy was performed in 53 patients. Allergen‐sIgE concentrations were measured with ISAC and ALEX2. Results for sIgE were statistically compared with each other, with SPT results and with clinical presentation of the patients. Results: Using ISAC as reference test for sIgE measurements, the average sensitivity of ALEX2 for PR‐10 allergens was 83.2% and the average specificity 88.0%. If only low sIgE concentrations were included, the sensitivity was 60.8% and the specificity 91.1%. Apple and hazelnut sensitizations were confirmed in most patients by concordance of sIgE and SPT results. Significant correlations were shown between clinical symptoms and Mal d 1‐ and Gly m 4‐sIgE levels measured by both tests and for Cor a 1‐sIgE levels measured by ALEX2. In eight patients, profilin related symptoms were supported by Hev b 8‐sensitization. Conclusion: Multiplex testing is beneficial to understand patient‐specific individual sensitization profiles and to providing personalized management recommendations. In the future, custom‐designed test kits might enable reducing costs of multiplex testing for specific patient groups without compromising the diagnostic value. [ABSTRACT FROM AUTHOR]

Non‐steroidal anti‐inflammatory drugs (NSAIDs) and other eicosanoid pathway modifiers are among the most ubiquitously used medications in the general population. Their broad anti‐inflammatory, antipyretic, and analgesic effects are applied against symptoms of respiratory infections, including SARS‐CoV‐2, as well as in other acute and chronic inflammatory diseases that often coexist with allergy and asthma. However, the current pandemic of COVID‐19 also revealed the gaps in our understanding of their mechanism of action, selectivity, and interactions not only during viral infections and inflammation, but also in asthma exacerbations, uncontrolled allergic inflammation, and NSAIDs‐exacerbated respiratory disease (NERD). In this context, the consensus report summarizes currently available knowledge, novel discoveries, and controversies regarding the use of NSAIDs in COVID‐19, and the role of NSAIDs in asthma and viral asthma exacerbations. We also describe here novel mechanisms of action of leukotriene receptor antagonists (LTRAs), outline how to predict responses to LTRA therapy and discuss a potential role of LTRA therapy in COVID‐19 treatment. Moreover, we discuss interactions of novel T2 biologicals and other eicosanoid pathway modifiers on the horizon, such as prostaglandin D2 antagonists and cannabinoids, with eicosanoid pathways, in context of viral infections and exacerbations of asthma and allergic diseases. Finally, we identify and summarize the major knowledge gaps and unmet needs in current eicosanoid research. [ABSTRACT FROM AUTHOR]

Immune modulation is a key therapeutic approach for allergic diseases, asthma and autoimmunity. It can be achieved in an antigen‐specific manner via allergen immunotherapy (AIT) or in an endotype‐driven approach using biologicals that target the major pathways of the type 2 (T2) immune response: immunoglobulin (Ig)E, interleukin (IL)‐5 and IL‐4/IL‐13 or non‐type 2 response: anti‐cytokine antibodies and B‐cell depletion via anti‐CD20. Coronavirus disease 2019 (COVID‐19) vaccination provides an excellent opportunity to tackle the global pandemics and is currently being applied in an accelerated rhythm worldwide. The vaccine exerts its effects through immune modulation, induces and amplifies the response against the severe acute respiratory syndrome coronavirus (SARS‐CoV‐2). Thus, as there may be a discernible interference between these treatment modalities, recommendations on how they should be applied in sequence are expected. The European Academy of Allergy and Clinical Immunology (EAACI) assembled an expert panel under its Research and Outreach Committee (ROC). This expert panel evaluated the evidence and have formulated recommendations on the administration of COVID‐19 vaccine in patients with allergic diseases and asthma receiving AIT or biologicals. The panel also formulated recommendations for COVID‐19 vaccine in association with biologicals targeting the type 1 or type 3 immune response. In formulating recommendations, the panel evaluated the mechanisms of COVID‐19 infection, of COVID‐19 vaccine, of AIT and of biologicals and considered the data published for other anti‐infectious vaccines administered concurrently with AIT or biologicals. [ABSTRACT FROM AUTHOR]

Earlier reports of differences in the EBV antibody profile of Long-COVID patients[6] could not be confirmed, possibly due to the small sample size analysed in our study. However, EBV DNA was detected in throat washings in 15/30 (50%) of Long-COVID patients while only in 4/20 (20%) of non-Long-COVID patients who had recovered from their SARS-CoV-2 infection ( I p i = .0411). To the Editor, Post-viral fatigue after SARS-CoV-2 infection is a major concern in the ongoing COVID-19 pandemic. [Extracted from the article]

It remains uncertain as to whether nutrient supplementation for the general population considered healthy could be useful in the prevention of RTIs, such as COVID‐19. In this systematic review and meta‐analysis, the evidence was evaluated for primary prevention of any viral respiratory tract infection (RTI) such as SARS‐CoV‐2, through supplementation of nutrients with a recognized role in immune function: multiple micronutrients, vitamin A, folic acid, vitamin B12, C, D, E, beta‐carotene, zinc, iron and long‐chain polyunsaturated fatty acids. The search produced 15,163 records of which 93 papers (based on 115 studies) met the inclusion criteria, resulting in 199,055 subjects (191,636 children and 7,419 adults) from 37 countries. Sixty‐three studies were included in the meta‐analyses, which was performed for children and adults separately. By stratifying the meta‐analysis by world regions, only studies performed in Asia showed a significant but heterogeneous protective effect of zinc supplementation on RTIs (RR 0.86, 95% CI 0.7–0.96, I2 = 79.1%, p =.000). Vitamin D supplementation in adults significantly decreased the incidence of RTI (RR 0.89, 95% CI 0.79–0.99, p =.272), particularly in North America (RR 0.82 95% CI 0.68–0.97), but not in Europe or Oceania. Supplementation of nutrients in the general population has either no or at most a very limited effect on prevention of RTIs. Zinc supplementation appears protective for children in Asia, whilst vitamin D may protect adults in the USA and Canada. In 10/115 (8.7%) studies post‐hoc analyses based on stratification for nutritional status was performed. In only one study zinc supplementation was found to be more effective in children with low zinc serum as compared to children with normal zinc serum levels. [ABSTRACT FROM AUTHOR]

Background: The COVID‐19 pandemic has affected health care systems unexpectedly. However, data focusing on practical considerations experienced by health care professionals (HCPs) providing care to allergic patients is scarce. Methods: Under the framework of the European Academy of Allergy and Clinical Immunology (EAACI), a panel of experts in the field of immunotherapy developed a 42‐question online survey, to evaluate real‐life consequences of the COVID‐19 pandemic in allergy practice. Results: The respondents in the survey were 618. About 80% of HCPs indicated being significantly affected in their allergy practice. A face‐to‐face visit reduction was reported by 93% of HCPs and about a quarter completely interrupted diagnostic challenges. Patients with severe uncontrolled asthma (59%) and anaphylaxis (47%) were prioritized for in‐person care. About 81% maintained an unaltered prescription of inhaled corticosteroids (ICS) in asthmatics. About 90% did not modify intranasal corticosteroids (INCS) in patients with allergic rhinitis. Nearly half of respondents kept biological prescriptions unmodified for asthma. About 50% of respondents kept their allergen immunotherapy (AIT) prescription patterns unchanged for respiratory allergies; 60% for insect venom allergies. Oral immunotherapy (OIT) for food allergies was initiated by 27%. About 20% kept carrying out up‐dosing without modifications and 14% changed to more prolonged intervals. Telemedicine practice was increased. Conclusions: HCPs providing care to allergic patients were affected during the pandemic in diagnostic, management, and therapeutic approaches, including AIT for respiratory, insect‐venom, and food allergies. Most HCPs maintained controller treatments for both asthma, and allergic rhinitis consistent with international recommendations, as well as biological agents in asthma. Remote tools are valuable in delivering allergy care. [ABSTRACT FROM AUTHOR]

Microbiota composition and associated metabolic activities are essential for the education and development of a healthy immune system. Microbial dysbiosis, caused by risk factors such as diet, birth mode, or early infant antimicrobial therapy, is associated with the inception of allergic diseases. In turn, allergic diseases increase the risk for irrational use of antimicrobial therapy. Microbial therapies, such as probiotics, have been studied in the prevention and treatment of allergic diseases, but evidence remains limited due to studies with high heterogeneity, strain‐dependent effectiveness, and variable outcome measures. In this review, we sketch the relation of microbiota with allergic diseases, the overuse and rationale for the use of antimicrobial agents in allergic diseases, and current knowledge concerning the use of bacterial products in allergic diseases. We urgently recommend 1) limiting antibiotic therapy in pregnancy and early childhood as a method contributing to the reduction of the allergy epidemic in children and 2) restricting antibiotic therapy in exacerbations and chronic treatment of allergic diseases, mainly concerning asthma and atopic dermatitis. Future research should be aimed at antibiotic stewardship implementation strategies and biomarker‐guided therapy, discerning those patients that might benefit from antibiotic therapy. [ABSTRACT FROM AUTHOR]

Abstract: Murine intestinal M-cells express α-l-fucose residues. We constructed α-l-fucose-targeting particles for oral immunotherapy of IgE-mediated allergy. Poly(d,l-lactic-co-glycolic acid)-microspheres were loaded with birch pollen allergens, and functionalised with the α-l-fucose specific Aleuria aurantia lectin (AAL). The AAL-microspheres had a size of 1–3μm, protected the entrapped allergens from gastric degradation and released 46.6±1.3% allergen over 21 days in vitro. Oral gavages of AAL-particles to naïve BALB/c mice induced birch pollen-specific IgG2a, but not IgG1 antibodies. We conclude that targeting allergens to α-l-fucose-receptor bearing cells using AAL-microspheres induces specific Th1-antibody responses possibly counteracting Th2-dominated allergy, and therefore provides a potentially useful formulation for oral immunotherapy. [Copyright &y& Elsevier]

In this study, we constructed particles applicable for oral immunotherapy of type I allergy by protecting allergens from digestion and supporting intestinal antigen uptake. Therefore, birch-pollen allergens were entrapped in poly(d,l-lactic-co-glycolic acid) microspheres by spray-drying rendering microspheres with a main population of 1–3 μm. Microspheres were further coated with wheat germ agglutinin (WGA) to target enterocytes. Coating with WGA did not alter the surface characteristics of the microspheres as demonstrated in scanning electron microscopy. Binding of WGA was specific and could be inhibited by chitotriose to 14.7 ± 6.9%. Comparable amounts of allergen were released from both particle-types with 46.3 ± 1.7% and 44.5 ± 2.6% during 21 days. Simulating gastric digestion in vitro, antigenicity of allergens entrapped in WGA-microspheres was preserved to 59.8 ± 1.5% even after 2 h. Feedings of BALB/c mice with WGA-microspheres induced higher levels of allergen-specific IgG-levels than gavages of uncoated microparticles or naked protein. Thus, we conclude that WGA-microspheres are suitable vehicles for oral delivery and mucosal targeting due to lectin-mediated bioadhesion. [Copyright &y& Elsevier]

Keywords: allergic rhinitis; ceruloplasmin; clinical reactivity; functional iron deficiency; microbes EN allergic rhinitis ceruloplasmin clinical reactivity functional iron deficiency microbes 2882 2886 5 09/03/21 20210901 NES 210901 ACKNOWLEDGEMENT We thank Miroslawa Matz for assistance during sample processing and storage. Despite increased iron mobilization efforts by the copper-containing ferroxidase ceruloplasmin, which also acts as an acute-phase reactant, allergic women had lower serum iron. Functional iron-deficiency in women with allergic rhinitis is associated with symptoms after nasal provocation and lack of iron-sequestering microbes. [Extracted from the article]

Further to the approval of the Coronavirus disease 2019 (COVID‐19) vaccine BNT162b2, several severe anaphylaxis cases occured within the first few days of public vaccination. An investigation is taking place to understand the cases and their triggers. The vaccine will be administered to a large number of individuals worldwide and there are raising concerns that severe adverse events might occur. With the current information, the European Academy of Allergy and Clinical Immunology (EAACI) states its position for the following preliminary recommendations that are to be revised as soon as more data emerge. To minimize the risk of severe allergic reactions in vaccinated individuals, it is urgently required to understand the specific nature of the reported severe allergic reactions, including the background medical history of the individuals affected and the mechanisms involved. To achieve this goal, all clinical and laboratory information should be collected and reported. Mild and moderate allergic patients should not be excluded from the vaccine as this could have a significant impact on reaching the goal of population immunity. Healthcare practitioners vaccinating against COVID‐19 are required to be sufficiently prepared to recognize and treat anaphylaxis properly with the ability to administer adrenaline. Further to vaccine administration, a mandatory observation period of at least 15 minutes should be followed for all individuals. The current data have not shown any higher risk for patients suffering from allergic rhinitis or asthma, and this message should be clearly stated by physicians to enable our patients to trust the vaccine. More than 30% of the population suffers from allergic diseases and the benefit of the vaccination clearly outweighs the risk of severe COVID‐19 development. [ABSTRACT FROM AUTHOR]

Eicosanoids are biologically active lipid mediators, comprising prostaglandins, leukotrienes, thromboxanes, and lipoxins, involved in several pathophysiological processes relevant to asthma, allergies, and allied diseases. Prostaglandins and leukotrienes are the most studied eicosanoids and established inducers of airway pathophysiology including bronchoconstriction and airway inflammation. Drugs inhibiting the synthesis of lipid mediators or their effects, such as leukotriene synthesis inhibitors, leukotriene receptors antagonists, and more recently prostaglandin D2 receptor antagonists, have been shown to modulate features of asthma and allergic diseases. This review, produced by an European Academy of Allergy and Clinical Immunology (EAACI) task force, highlights our current understanding of eicosanoid biology and its role in mediating human pathology, with a focus on new findings relevant for clinical practice, development of novel therapeutics, and future research opportunities. [ABSTRACT FROM AUTHOR]

While the world is facing an unprecedented pandemic with COVID‐19, patients with chronic diseases need special attention and if warranted adaptation of their regular treatment plan. In children, allergy and asthma are among the most prevalent non‐communicable chronic diseases, and healthcare providers taking care of these patients need guidance. At the current stage of knowledge, children have less severe symptoms of COVID‐19, and severe asthma and immunodeficiency are classified as risk factors. In addition, there is no evidence that currently available asthma and allergy treatments, including antihistamines, corticosteroids, and bronchodilators, increase the risk of severe disease from COVID‐19. Most countries affected by COVID‐19 have opted for nationwide confinement, which means that communication with the primary clinician is often performed by telemedicine. Optimal disease control of allergic, asthmatic, and immunodeficient children should be sought according to usual treatment guidelines. This statement of the EAACI Section on Pediatrics puts forward six recommendations for the management of childhood allergies and immunodeficiencies based on six underlying facts and existing evidence. [ABSTRACT FROM AUTHOR]

Background: Food processing, including heat‐treatment, can affect protein structure and stability, and consequently affect protein immunogenicity and allergenicity. A few studies have shown that structural changes induced by heat‐treatment impact the intestinal protein uptake and suggest this as a contributing factor for altered allergenicity. Objective: To investigate the impact of heat‐treatment of a whey‐based protein product on allergenicity and tolerogenicity as well as on intestinal uptake in various animal models. Methods: Immunogenicity and sensitizing capacity of the heat‐treated whey product were compared to that of the unmodified product by intraperitoneal and oral exposure studies, while tolerogenic properties were assessed by oral primary prevention and desensitization studies in high‐IgE responder Brown Norway rats. Results: Heat‐treatment of whey induced partial protein denaturation and aggregation, which reduced the intraperitoneal sensitizing capacity but not immunogenicity. In contrast, heat‐treatment did not influence the oral sensitizing capacity, but the heat‐treated whey showed a significantly reduced eliciting capacity compared to unmodified whey upon oral challenge. Heat‐treatment did not reduce the tolerogenic properties of whey, as both products were equally good at preventing sensitization in naïve rats as well as desensitizing already sensitized rats. Results from inhibitory ELISA and immunoblots with sera from sensitized rats demonstrated that heat‐treatment caused an altered protein and epitope reactivity. Protein uptake studies showed that heat‐treatment changed the route of uptake with less whey being absorbed through the epithelium but more into the Peyer's patches. Conclusion and Clinical Relevance: These results support the notion that the physicochemical features of proteins affect their route of uptake and that the route of uptake may affect the protein allergenicity. Furthermore, the study highlights the potential for heat‐treatment in the production of efficient and safe cow's milk protein‐based products for prevention and treatment of cow's milk allergy. [ABSTRACT FROM AUTHOR]

To fully understand the role of diet diversity on allergy outcomes and to set standards for conducting research in this field, the European Academy of Allergy and Clinical Immunology Task Force on Diet and Immunomodulation has systematically explored the association between diet diversity and allergy outcomes. In addition, a detailed narrative review of information on diet quality and diet patterns as they pertain to allergic outcomes is presented. Overall, we recommend that infants of any risk category for allergic disease should have a diverse diet, given no evidence of harm and some potential association of benefit in the prevention of particular allergic outcomes. In order to harmonize methods for future data collection and reporting, the task force members propose relevant definitions and important factors for consideration, when measuring diet diversity in the context of allergy. Consensus was achieved on practice points through the Delphi method. It is hoped that the definitions and considerations described herein will also enable better comparison of future studies and improve mechanistic studies and pathway analysis to understand how diet diversity modulates allergic outcomes. [ABSTRACT FROM AUTHOR]

Background: Food allergy is associated with a high personal health and economic burden. For immunomodulation toward tolerance, food compounds could be chemically modified, for example, by posttranslational protein nitration, which also occurs via diet‐derived nitrating agents in the gastrointestinal tract. Objective: We sought to analyze the effect of pretreatment with nitrated food proteins on the immune response in a mouse food allergy model and on human monocyte‐derived dendritic cells (moDCs) and PBMCs. Methods: The model allergen ovalbumin (OVA) was nitrated in different nitration degrees, and the secondary structures of proteins were determined by circular dichroism (CD). Allergy‐preventive treatment with OVA, nitrated OVA (nOVA), and maximally nitrated OVA (nOVAmax) were performed before mice were immunized with or without gastric acid‐suppression medication. Antibody levels, regulatory T‐cell (Treg) numbers, and cytokine levels were evaluated. Human moDCs or PBMCs were incubated with proteins and evaluated for expression of surface markers, cytokine production, and proliferation of Th2 as well as Tregs. Results: In contrast to OVA and nOVA, the conformation of nOVAmax was substantially changed. nOVAmax pretreated mice had decreased IgE as well as IgG1 and IgG2a levels and Treg numbers were significantly elevated, while cytokine levels remained at baseline level. nOVAmax induced a regulatory DC phenotype evidenced by a decrease of the activation marker CD86 and an increase in IL‐10 production and was associated with a higher proliferation of memory Tregs. Conclusion: Oral pretreatment with highly nitrated proteins induces a tolerogenic immune response in the food allergy model and in human immune cells. [ABSTRACT FROM AUTHOR]

The prevalence of allergic diseases such as allergic rhinitis, asthma, food allergy, and atopic dermatitis has increased dramatically during the last decades, which is associated with altered environmental exposures and lifestyle practices. The purpose of this review was to highlight the potential role for dietary fatty acids, in the prevention and management of these disorders. In addition to their nutritive value, fatty acids have important immunoregulatory effects. Fatty acid‐associated biological mechanisms, human epidemiology, and intervention studies are summarized in this review. The influence of genetics and the microbiome on fatty acid metabolism is also discussed. Despite critical gaps in our current knowledge, it is increasingly apparent that dietary intake of fatty acids may influence the development of inflammatory and tolerogenic immune responses. However, the lack of standardized formats (ie, food versus supplement) and standardized doses, and frequently a lack of prestudy serum fatty acid level assessments in clinical studies significantly limit our ability to compare allergy outcomes across studies and to provide clear recommendations at this time. Future studies must address these limitations and individualized medical approaches should consider the inclusion of specific dietary factors for the prevention and management of asthma, food allergy, and atopic dermatitis. [ABSTRACT FROM AUTHOR]

The current allergenicity assessment of novel proteins is based on the EFSA GMO guidance. Recently, EFSA launched a new guidance document on allergenicity assessment of GM plants (2017). This document describes, amongst other topics, the new scientific and regulatory developments on in vitro protein digestibility tests. The EFSA GMO Panel stated that for in vitro protein digestibility tests, additional investigations are needed before any additional recommendation in the form of guidance can be provided. To this end, an interim phase is considered necessary to evaluate the revisions to the in vitro gastrointestinal digestion test, proposed by EFSA. This prompted the establishment of a joint workshop through two COST Action networks: COST Action ImpARAS and COST Acton INFOGEST. In 2017, a workshop was organised to discuss the relevance of digestion in allergenicity risk assessment and how to potentially improve the current methods and readouts. The outcome of the workshop is that there is no rationale for a clear readout that is predictive for allergenicity and we suggest to omit the digestion test from the allergenicity assessment strategy for now, and put an effort into filling the knowledge gaps as summarized in this paper first. • Protein digestion is relevant for allergenicity of some proteins, but not for all. • It is not clear yet how different factors exactly influence digestion and how these factors can be included. • Including all factors will complicate the elaboration of a simple and predictive digestion assay. • There is no rationale for a clear readout that is predictive for allergenicity. • We suggest to omit the digestion test from the allergenicity assessment for now and put effort into filling the knowledge gaps. [ABSTRACT FROM AUTHOR]

To improve current mucosal allergen immunotherapy Vibrio cholerae neuraminidase (NA) was evaluated as a novel epithelial targeting molecule for functionalization of allergen-loaded, poly(D,L-lactide- co -glycolide) (PLGA) microparticles (MPs) and compared to the previously described epithelial targeting lectins wheat germ agglutinin (WGA) and Aleuria aurantia lectin (AAL). All targeters revealed binding to Caco-2 cells, but only NA had high binding specificity to α-L fucose and monosialoganglioside-1. An increased transepithelial uptake was found for NA-MPs in a M-cell co-culture model. NA and NA-MPs induced high levels of IFN-γ and IL10 in naive mouse splenocytes and CCL20 expression in Caco-2. Repeated oral gavage of NA-MPs resulted in a modulated, allergen-specific immune response. In conclusion, NA has enhanced M-cell specificity compared to the other targeters. NA functionalized MPs induce a Th1 and T-regulatory driven immune response and avoid allergy effector cell activation. Therefore, it is a promising novel, orally applied formula for allergy therapy. [ABSTRACT FROM AUTHOR]

Previous studies have attributed to the cocoa powder the capacity to attenuate the immune response in a rat oral sensitization model. To gain a better understanding of cocoa-induced mechanisms at small intestinal level, 3-week-old female Lewis rats were fed either a standard diet or a diet containing 10% cocoa for 4 weeks with or without concomitant oral sensitization with ovalbumin (OVA). Thereafter, we evaluated the lymphocyte composition of the Peyer's patches (PPL), small intestine epithelium (IEL) and lamina propria (LPL). Likewise, gene expression of several immune molecules was quantified in the small intestine. Moreover, histological samples were used to evaluate the proportion of goblet cells, IgA+ cells and granzyme+cells as well. In cocoa-fed animals, we identified a five-time reduction in the percentage of IgA+ cells in intestinal tissue together with a decreased proportion of TLR4+ IEL. Analyzing the lymphocyte composition, almost a double proportion of TCRγδ+cells and an increase of NK cell percentage in PPL and IEL were found. In addition, a rise in CD25+, CD103+ and CD62L- cell proportions was observed in CD4+ PPL from cocoa-fed animals, along with a decrease in gene expression of CD11b, CD11c and IL-10. These results suggest that changes in PPL and IEL composition and in the gene expression induced by the cocoa diet could be involved, among other mechanisms, on its tolerogenic effect. [ABSTRACT FROM AUTHOR]

In our mouse model, gastric acid-suppression is associated with antigen-specific IgE and anaphylaxis development. We repeatedly observed non-responder animals protected from food allergy. Here, we aimed to analyse reasons for this protection. Ten out of 64 mice, subjected to oral ovalbumin (OVA) immunizations under gastric acid-suppression, were non-responders without OVA-specific IgE or IgG1 elevation, indicating protection from allergy. In these non-responders, allergen challenges confirmed reduced antigen uptake and lack of anaphylactic symptoms, while in allergic mice high levels of mouse mast-cell protease-1 and a body temperature reduction, indicative for anaphylaxis, were determined. Upon OVA stimulation, significantly lower IL-4, IL-5, IL-10 and IL-13 levels were detected in non-responders, while IL-22 was significantly higher. Comparison of fecal microbiota revealed differences of bacterial communities on single bacterial Operational-Taxonomic-Unit level between the groups, indicating protection from food allergy being associated with a distinct microbiota composition in a non-responding phenotype in this mouse model. [ABSTRACT FROM AUTHOR]

Food allergy is a major health problem of increasing concern. The insufficiency of protein sources for human nutrition in a world with a growing population is also a significant problem. The introduction of new protein sources into the diet, such as newly developed innovative foods or foods produced using new technologies and production processes, insects, algae, duckweed, or agricultural products from third countries, creates the opportunity for development of new food allergies, and this in turn has driven the need to develop test methods capable of characterizing the allergenic potential of novel food proteins. There is no doubt that robust and reliable animal models for the identification and characterization of food allergens would be valuable tools for safety assessment. However, although various animal models have been proposed for this purpose, to date, none have been formally validated as predictive and none are currently suitable to test the allergenic potential of new foods. Here, the design of various animal models are reviewed, including among others considerations of species and strain, diet, route of administration, dose and formulation of the test protein, relevant controls and endpoints measured. [ABSTRACT FROM AUTHOR]

Characterization of serum glycoprotein N-glycans with matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) in positive-ion mode needs a derivatization step to stabilize and neutralize the negative charge on sialic acids. The acidic sugars are attached to the end of glycoproteins, glycolipids or gangliosides. Here, we present a method for sialic acid stabilization via modification based on derivatization of carboxylic acid group activated with 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMTMM) with methylamine. DMTMM substitutes in many processes N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride and N-hydroxysuccinimide (EDC/NHS) as activation reagent due to its better performance and higher stability in water. Glycosylated proteins are used as solid phase support for glycan derivatization and purification from excess of derivatization reagents. We evaluated our glycan analysis method in murine sera and intestinal lavages. The stabilization of sialic acid enables a complete conservation of the glycan structures, in contrast to other methods where sialic acids are partially lost. In BALB/c mouse sera, we detected predominantly mono- and di-sialylated N-glycans with mostly N-Glycolylneuraminic acid (Neu5Gc) and only trace amounts of N-Acetyl neuraminic acid (Neu5Ac). BALB/c mouse intestinal lavages glycoproteins contained asialo N-glycans. DMTMM-mediated methylamidation of N-glycans for MALDI mass spectrometry analysis is a fast and cheap method for structurally conserved glycan derivatization. [Display omitted] • MALDI mass spectrometry analysis for characterization of N-glycans. • Stabilization and neutralization of sialic acids via methylamidation. • DMTMM mediated modifications for cost-effective high yield synthesis. • Site specific N-glycan profile analysis in sera and intestinal lavages of BALB/c mouse. [ABSTRACT FROM AUTHOR]

Background: We revealed in previous studies that nitration of food proteins reduces the risk of de novo sensitization in a murine food allergy model. In contrast, in situations with preformed specific IgE antibodies, in vitro experiments suggested an increased capacity of effector cell activation by nitrated food proteins. Objective: The aim of this study was to investigate the influence of protein nitration on the effector phase of food allergy. Design: BALB/c mice were immunized intraperitoneally (i.p.) with the milk allergen β-lactoglobulin (BLG) or the egg allergen ovomucoid (OVM), followed by intragastric (i.g.) gavages to induce a strong local inflammatory response and allergen-specific antibodies. Subsequently, naïve and allergic mice were intravenously (i.v.) challenged with untreated, sham-nitrated or nitrated BLG or OVM. Anaphylaxis was monitored by measuring core body temperature and determination of mouse mast cell protease-1 (mMCP-1) levels in blood. Results: A significant drop of body temperature accompanied with significantly elevated concentrations of the anaphylaxis marker mMCP-1 were only observed in BLG allergic animals challenged with nitrated BLG and not in OVM allergic mice challenged with nitrated OVM. SDS-PAGE and circular dichroism analysis of the differentially modified allergens revealed an effect of nitration on the secondary protein structure exclusively for BLG together with enhanced protein aggregation. Conclusion: Our data suggest that nitration affects differently the food allergens BLG and OVM. In the case of BLG, structural changes favored dimerization possibly explaining the increased anaphylactic reactivity in BLG allergic animals. [ABSTRACT FROM AUTHOR]

Abstract: Background: Sphingosine-1-phosphate (S1P) influences activation, migration and death of immune cells. Further, S1P was proposed to play a major role in the induction and promotion of allergic diseases. However, to date only limited information is available on the role of S1P in food allergy. Objective: We aimed to investigate the role of sphingosine-kinase (SphK) 1 and 2, the enzymes responsible for endogenous S1P production, on the induction of food allergy. Methods and results: Human epithelial colorectal CaCo2 cells stimulated in vitro with S1P revealed a decrease of transepithelial resistance and enhanced transport of FITC labeled OVA. We studied the effect of genetic deletion of the enzymes involved in S1P production on food allergy induction using a mouse model of food allergy based on intragastrically (i.g.) administered ovalbumin (OVA) with concomitant acid-suppression. Wild-type (WT), SphK1−/− and SphK2−/− mice immunized with OVA alone i.g. or intraperitoneally (i.p.) were used as negative or positive controls, respectively. SphK1- and SphK2-deficient mice fed with OVA under acid-suppression showed reduced induction of OVA specific IgE and IgG compared to WT mice, but had normal responses when immunized by the intraperitoneal route. Flow cytometric analysis of spleen cells revealed a significantly reduced proportion of CD4+ effector T-cells in both SphK deficient animals after oral sensitization. This was accompanied by a reduced accumulation of mast cells in the gastric mucosa in SphK-deficient animals compared to WT mice. Furthermore, mouse mast cell protease-1 (mMCP-1) levels, an IgE-mediated anaphylaxis marker, were reliably elevated in allergic WT animals. Conclusion: Modulation of the S1P homeostasis by deletion of either SphK1 or SphK2 alters the sensitization and effector phase of food allergy. [Copyright &y& Elsevier]

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a severe multi-systemic disease characterized by debilitating fatigue that is not relieved by rest. The causes of the disease are still largely unexplained, and no causative treatment is currently available. Changes in the immune response are considered as fundamental in the development of ME/CFS. Thus, we aimed to evaluate the immunological profile of ME/CFS patients in a retrospective data analysis. As part of the routine workup for ME/CFS patients, a differential blood count, leukocyte subtyping, and quantification of immunoglobulins and IgG subclasses, as well as a complement analysis, was performed. Out of 262 ME/CFS patients, 64.9% had a reduction or deficiency in at least one of the listed immune parameters. In contrast, 26.3% showed signs of immune activation or inflammation. A total of 17.6% of the ME/CFS patients had an unclassified antibody deficiency, with IgG3 and IgG4 subclass deficiencies as the most common phenotypes. Reduced MBL (mannose-binding lectin) levels were found in 32% of ME/CFS patients, and MBL deficiency in 7%. In summary, the present results confirmed the relevance of immune dysfunction in ME/CFS patients underlining the involvement of a dysfunctional immune response in the disease. Thus, immune parameters are relevant disease biomarkers, which might lead to targeted therapeutic approaches in the future. [ABSTRACT FROM AUTHOR]

The treatment of dyspeptic disorders with anti-acids leads to an increased risk of sensitization against food allergens. As these drugs are taken by 30-50% of pregnant women due to reflux and heart-burn, we aimed here to investigate the impact of maternal therapy with anti-acids on the immune response in the offspring in a murine model. Codfish extract as model allergen was fed with or without sucralfate, an anti-acid drug, to pregnant BALB/c mice during pregnancy and lactation. These mothers developed a codfish-specific allergic response shown as high IgG1 and IgE antibody levels and positive skin tests. In the next step we analyzed whether this maternal sensitization impacts a subsequent sensitization in the offspring. Indeed, in stimulated splenocytes of these offspring we found a relative Th2-dominance, because the Th1- and T-regulatory cytokines were significantly suppressed. Our data provide evidence that the anti-acid drug sucralfate supports sensitization against food in pregnant mice and favors a Th2-milieu in their offspring. From these results we propose that anti-acid treatment during pregnancy could be responsible for the increasing number of sensitizations against food allergens in young infants. [ABSTRACT FROM AUTHOR]

Abstract: For elderly people, epidemiological data are rare for respiratory allergies and completely missing for food allergies. The aim of this study was to examine the prevalence and risk factors for sensitizations in 109 people with a mean age of 77 years, who are living in a geriatric nursing home. The cross-sectional study included a detailed interview, skin prick tests, and serum tests for specific and total IgE, IFN-γ, and ST2, a marker for Th2-lymphocyte activity. Almost all study subjects (n =101) suffered from co-morbidity, 14 from type I allergy, 25 from gastrointestinal disorders treated with anti-ulcer drugs, 25 were chronic alcoholics and 21 were smokers. The total IgE levels were significantly higher in men (P =0.025), and not affected by smoking or alcohol consumption. Skin prick tests were positive in 41.7% of tested patients. Specific IgE to respiratory allergens was found in 40.4% of all patients and was elevated in men (P =0.013), with a significant correlation to smoking (P =0.029). Specific IgE to food allergens was detected in 24.8%, apparently without connection to the investigated risk factors. However, positive skin prick tests with food allergens could be correlated with chronic alcohol consumption (P =0.036). The intake of anti-ulcer medication was significantly correlated with elevated ST2 levels as an indirect readout for Th2-cell activity (P <0.001). The risk factors for sensitization in elderly to respiratory allergens were chronic damage of respiratory epithelia due to smoking, and for sensitization to food allergens chronic alcohol consumption. [Copyright &y& Elsevier]