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Chronic spontaneous urticaria (CSU) is a common skin disease without an etiology in the vast majority of cases. The similarity of symptoms and pathology to allergen-induced skin reactions supports that skin mast cell IgE receptor activation is also involved in CSU. Accumulating evidence also supports a role for blood basophils in disease expression. Blood basopenia is noted in active CSU disease with the recruitment of blood basophils to skin lesion sites. Blood basophils further display altered IgE receptor mediated degranulation patterns in two phenotypes that improve in remission. In active CSU subjects, changes in IgE receptor signaling molecule expression levels accompany the altered degranulation function in blood basophils. The success of therapies targeting IgE in CSU patients have also shown that altered blood basophil phenotypes and enumeration have potential use as a disease biomarker.

The signs and symptoms of chronic urticaria (CU) are caused by the activation and degranulation of skin mast cells (MCs). Recent studies have added to our understanding of how and why skin MCs are involved and different in CU. Also, novel and relevant mechanisms of MC activation in CU have been identified and characterized. Finally, the use of MC-targeted and MC mediator-specific treatments has helped to better define the role of the skin environment, the contribution of specific MC mediators, and the relevance of MC crosstalk with other cells in the pathogenesis of CU. Here, we review these recent findings and their impact on our understanding of CU, with a focus on chronic spontaneous urticaria (CSU). Also, we highlight open questions, issues of controversy, and unmet needs, and we suggest what studies should be performed moving forward.

Abstract Background Helminths are potent immunomodulators and in their chronic infection state they may protect against allergy‐related disease and atopy. However, they are also known for inducing allergic conditions. This study aimed to assess the association between helminths, atopy and allergic conditions. Methods A total of 461 school children participated in this cross‐sectional study. Data on allergic symptoms and a range of confounding variables was gathered from parents via an interviewer‐led questionnaire. Skin sensitization to house dust mite and cockroaches was analyzed, and a stool sample was collected for helminth analysis. Serum total Immunoglobulin E using enzyme‐linked immunosorbent assay and eosinophil count were also measured. Results Overall sensitivity to both allergens was 2.4%. Self‐reported allergic outcomes in the last 12 months for the 461 participants had been : wheezing 3.7%, asthma 2.2%, eczema 13.2% and hay fever 6.9%. Overall, the prevalence of helminth infection was 11.9% (53/444). A borderline significant association was found between atopy and any allergy symptoms (odds ratio [OR]: 3.32, 95% confidence interval [95% CI: 0.99, 11.1], p = .052). There was no significant association between helminths and atopy (OR: 0.64 [95% CI: 0.29, 1.41], p = .268) and also between helminths and allergic symptoms (OR: 0.64 [95% CI: 0.29, 1.41], p = .268). Bivariate analysis showed keeping an animal in the house increases the risk of atopy while maternal and paternal history of allergy increases the risk of developing allergic symptoms in the children. Conclusion and clinical relevance This study found a non‐significant inverse association between helminths infection and atopy and allergic disorders, likely due to reduced statistical power, resulting in a lower prevalence of atopy and allergic conditions. A high powered longtitudinal study is necessary to explore the casuality and potential therapeutic benefits of helminths for allergic disorders.

Food protein-induced allergic proctocolitis (FPIAP) is a non-IgE-mediated allergic condition that presents with hematochezia in otherwise healthy infants. It is most commonly induced by cow's milk protein via breast milk or formula. The prognosis for FPIAP is generally considered favorable with most infants achieving symptomatic resolution after diet modification. Most infants go on to tolerate the offending foods by 1–3 years of age. Over 8 years at our institution, five patients were identified and noted to have FPIAP to cow's milk during infancy with subsequent development of IgE-mediated allergic reaction to cow's milk and other foods. All five cases developed other atopic disorders (atopic dermatitis in four cases). IgE-mediated cow's milk allergy has persisted beyond the preschool years in at least two patients (currently 8 and 16 years old). For three of the patients, the IgE-mediated reaction to cow's milk was severe with development of anaphylaxis or angioedema. In addition, three patients experienced anaphylaxis or angioedema to allergens other than milk. While FPIAP is a non-IgE-mediated process traditionally thought not to progress past the first year of life, some infants with FPIAP develop severe, persistent IgE-mediated cow's milk allergy. To our knowledge, this is the first detailed clinical description of such patients.

Mast cells are activated through a variety of different receptors to release preformed granules and mediators synthesized de novo. However, the physiology and function of mast cells are not fully understood. Traditional studies of mast cell activation in humans have utilized cultures of tissue-derived mast cells including CD34+ progenitor cells or well-characterized commercially available cell lines. One limitation of these methods is that mast cells are no longer in a natural state. Therefore, their applicability to human skin disorders may be limited. Human skin explant models have been utilized to investigate the short-term effects of cell mediators, drugs, and irritants on skin while avoiding the ethical concerns surrounding in vivo stimulation studies with non-approved agents. Nonetheless, few studies have utilized intact human tissue to study mast cell degranulation. This “Methods” paper describes the development and application of an intact skin explant model to study human mast cell activation. In this manuscript, we share our protocol for setting up ex vivo human skin explants and describe the results of stimulation experiments and techniques to minimize trauma-induced histamine release. Skin explants were generated using de-identified, full-thickness, non-diseased skin specimens from plastic and reconstructive surgeries. Results were reproducible and demonstrated FcɛRI- and MRGPRX2-induced mediator release which was inhibited with the use of a BTK inhibitor and QWF, respectively. Thus, this explant model provides a quick and accessible method of assessing human skin mast cell activation and inhibition.

Inner ear disorders have a variety of causes, and many factors can contribute to the exacerbation of cochlear and vestibular pathology. This systematic review aimed to analyze clinical data on the coexistence and potential causal interaction between allergic diseases and inner ear conditions. A search of PubMed and Web of Science identified 724 articles, of which 21 were selected for full-text analysis based on inclusion and exclusion criteria. The epidemiologic evidence found overwhelmingly supports an association between allergic disease and particular inner ear disorders represented by a high prevalence of allergic reactions in some patients with Ménière’s disease (MD), idiopathic sudden sensorineural hearing loss (ISSHL), and acute low-tone hearing loss (ALHL). In addition, patients with MD, ISSHL, and ALHL had higher levels of total serum IgE than healthy subjects. Finally, in some cases, changes in cochlear potential may have been induced by antigen exposure, while desensitization alleviated allergy and inner ear-related symptoms. The exact mechanism of interaction between the auditory/vestibular and immune systems is not fully understood, and further clinical and basic research is needed to understand the relationship between the two systems fully.

Background: Occupational exposure to wood dust, generated by various individual wood species, both softwood and hardwood, has been extensively documented as a causative factor for reduced lung function, frequent respiratory symptoms, and increased immunological responses in wood workers. This study explores the impact of wood dust from mixed tropical hardwood species on lung function, respiratory symptoms, and Immunoglobulin (Ig) E and G levels. Methods: A cross-sectional study was conducted among wood workers at the Accra Timber Market and a control group from the University of Ghana. Particulate matter (PM) was sampled using a Minivol Sampler set to a flow rate of 5 l/min. Respiratory symptoms were assessed using questions adapted from the British Medical Research Council (MRC) questionnaire (1960). Lung volumes and airflow rates were measured using a spirometer. Total serum IgE and IgG levels were quantified using ELISA. Results: No significant differences were observed between the wood workers and the controls for demographic variables. Wood workers exhibited a significantly higher prevalence of respiratory symptoms, particularly rhinitis, with many reporting the absence of symptoms during holidays. Lung function parameters (VC, FEV1, FEV1%, PEFR, and FEF25-75%) were significantly reduced (p

Abstract Background Several studies describe an inverse statistical relationship between the presence of an allergy and development of cancer. However, the immunological mechanism involved in the relationship between these two degenerative diseases has not been explored. Aims The main objective of this study was to explore the possibility that the lymphocyte T helper (Th) 2 response, a characteristic of allergy, induces recognition of tumor antigens. Methods and results Patients with a clinical diagnosis of breast ductal carcinoma were included. Histopathological markers related to proliferation of tumor cells were determined (Her‐2‐neu, Ki‐67, estrogen receptor, and progesterone receptor). IHC was performed using IgE antibodies purified from an allergy patient and from each biopsy donor patient. Serum concentrations of cytokines representative of Th1 and Th2 inflammatory responses were determined. A total of 14 patients with a confirmed diagnosis of breast ductal carcinoma were included. IHC performed on biopsies showed a weak response when using purified IgE antibodies from an allergy patient; however, IHC using the IgE of each patient as the primary antibody showed an intense and highly specific signal. Serum concentrations of cytokines of the Th2 response, that is, IL‐4 (130.5 pg/mL (116–135 pg/mL)), IL‐5 (202 pg/mL (191–213 pg/mL)), and IL‐13 (105.5 pg/mL (98–117 pg/mL)), were significantly higher than those of the Th1 response, that is, IL‐6 (86 pg/mL (79–90 pg/mL)) and INF‐γ (93 pg/mL (79–99 pg/mL)). Conclusion Purified IgE antibodies specifically recognize tumor cells in breast ductal carcinoma.

Background: Allergic parotitis (AP), due to its non-specific symptoms, frequently poses a diagnostic challenge, leading to cases being overlooked or misdiagnosed by clinicians. Objective: This study aimed to elucidate detailed clinical characteristics and common diagnostic indicators of AP. Methods: A comprehensive review and analysis of medical records was conducted from patients diagnosed with AP, encompassing demographic, clinical, and laboratory data, at the Affiliated Stomatological Hospital of Nanjing Medical University between January 2019 and March 2022. Results: The study enrolled 17 patients, evidenced by an average age of 36.00 ± 12.95 years. Common presentations of AP among the patients included notable symptoms such as parotid gland swelling, associated pain, and xerostomia. Ten patients had other atopic diseases. Palpation revealed the affected parotid glands to be soft and nodular, with an elevated local skin temperature. The unstimulated whole saliva flow rate was decreased. Ultrasonography demonstrated increased volume, reduced echo heterogeneity, and lymph node enlargement in the affected parotid glands. All cases observed increased serum salivary amylase and total IgE levels. Investigation of food allergens and inhaled allergen-specific IgE showed that all patients had suspected food allergies. Food provocation tests (FPT) induced AP in 13 cases, confirming the role of food allergens. Conclusion: Food allergens are involved in the etiology of AP, underscoring the importance of comprehensive clinical evaluation, including symptoms, signs, and confirmatory auxiliary tests, such as FPT, for accurate diagnosis and differentiation from other salivary gland pathologies.

The rising global incidence of IgE-mediated allergic reactions poses a significant challenge to the quality of life of affected individuals and to healthcare systems, with current treatments being limited in effectiveness, safety, and disease-modifying capabilities. IgE acts by sensitizing the high-affinity IgE receptor FcεRI expressed by mast cells and basophils, tuning these cells for inflammatory degranulation in response to future allergen encounters. In recent years, IgG has emerged as an essential negative regulator of IgE-dependent allergic inflammation. Mechanistically, studies have proposed different pathways by which IgG can interfere with the activation of IgE-mediated inflammation. Here, we briefly summarize the major proposed mechanisms of action by which IgG controls the IgE-FcεRI inflammatory axis and how those mechanisms are currently applied as therapeutic interventions for IgE-mediated inflammation.

BackgroundAsthma and allergic rhinitis (AR) can coexist and cause disabilities. This study aimed to assess the association between AR, asthma control, asthma-related quality of life, and other comorbidities.MethodsA cross-sectional study was conducted in adults with asthma in six hospitals in Thailand. The outcomes were association of asthma control assessed by the asthma control test (ACT), AR, and asthma comorbidities. Not-well-controlled asthma was defined as ACT scores ≤22. The severity of AR was determined by visual analog scale (VAS). Severe AR was defined as VAS ≥5. Asthma-related quality of life (AQLQ), comorbidities, and total IgE were recorded.ResultsA total of 682 asthmatic patients were included. Median (IQR) age was 58.0 (47.0–64.0) years. 69.9% were female. Not-well-controlled asthma was present in 44.7%. The prevalence of AR was 86.1%. Moderate/severe persistent AR was diagnosed in 21.7% and severe AR was diagnosed in 30.2% of the patients. Inhaled corticosteroid-containing regimens were prescribed in 97.7% of patients. Intranasal corticosteroid and antihistamine were prescribed in 65.7 and 31.7%, respectively. Patients with not-well-controlled asthma had higher body mass index, VAS scores, proportions of pollution exposure, aeroallergen sensitization, severe AR, nasal polyp, urticaria, food allergy, gastroesophageal reflux disease, depression and anxiety, peptic ulcer, and asthma exacerbations, but younger age, lower AQLQ scores, and lower FEV1. Correlation was found between AR severity and ACT (r = −0.461, p

La incidencia y prevalencia de las enfermedades alérgicas han aumentado en los últimos años, por lo que se han estudiado los alergenos, desde el punto de vista inmunológico, estructural y funcional. La inmunoglobulina E es fundamental en los fenómenos alérgicos donde su concentración aumenta notoriamente. Con el fin de establecer un antecedente mediante la determinación de IgE total por el método de quimioluminiscencia como indicador de enfermedad alérgica en pacientes en el Hospital Dr. Rafael Rodríguez Zambrano, se realizó un estudio de tipo observacional, descriptivo, retrospectivo y de corte transversal en 267 pacientes que acudieron a realizarse la prueba de IgE durante el año 2019, de los cuales el sexo femenino fue el más prevalente, con una relación directa entre los valores de eosinófilos e IgE con un predominio de valores iguales o menores a 190 UI/ml .Con la prueba de chi cuadrado se obtuvo una diferencia significativa estadísticamente, predominando la asociación entre los valores normales de eosinófilos y el valor de la IgE, Spearman mostró una asociación entre ambas variables, destacando una eosinofilia en el grupo de IgE entre 1000 y 1200 UL/ml. Se concluye que la inmunoglobulina E, es una prueba fehaciente para realizar un diagnóstico de alergia

AMG 256 is a bi-specific, heteroimmunoglobulin molecule with an anti-PD-1 antibody domain and a single IL-21 mutein domain on the C-terminus. Nonclinical studies in cynomolgus monkeys revealed that AMG 256 administration led to the development of immunogenicity-mediated responses and indicated that the IL-21 mutein domain of AMG 256 could enhance the anti-drug antibody response directed toward the monoclonal antibody domain. Anti-AMG 256 IgE were also observed in cynomolgus monkeys. A first-in-human (FIH) study in patients with advanced solid tumors was designed with these risks in mind. AMG 256 elicited ADA in 28 of 33 subjects (84.8%). However, ADA responses were only robust and exposure-impacting at the 2 lowest doses. At mid to high doses, ADA responses remained low magnitude and all subjects maintained exposure, despite most subjects developing ADA. Limited drug-specific IgE were also observed during the FIH study. ADA responses were not associated with any type of adverse event. The AMG 256 program represents a unique case where nonclinical studies informed on the risk of immunogenicity in humans, due to the IL-21-driven nature of the response.

Anaphylaxis is a potentially life-threatening multi-system allergic reaction to a biological trigger resulting in the release of potent inflammatory mediators from mast cells and basophils and causing symptoms in at least two organ systems that generally include skin, lungs, heart, or gastrointestinal tract in any combination. One exception is profound hypotension as an isolated symptom. There are two types of triggers of anaphylaxis: immunologic and non-Immunologic. Immunologic anaphylaxis is initiated when a foreign antigen directly binds to IgE expressed on mast cells or basophils and induces the release of histamine and other inflammatory substances resulting in vasodilation, vascular leakage, decreased peripheral vascular resistance, and heart muscle depression. If left untreated, death by shock (profound hypotension) or asphyxiation (airway obstruction) can occur. The non-immunologic pathway, on the other hand, can be initiated in many ways. A foreign substance can directly bind to receptors of mast cells and basophils leading to degranulation. There can be immune complex activation of the classical complement cascade with the release of anaphylatoxins C3a and C5a with subsequent recruitment of mast cells and basophils. Finally, hyperosmolar contrast agents can cause blood cell lysis, enzyme release, and complement activation, resulting in anaphylactoid (anaphylactic-like) symptoms. In this report we emphasize the recruitment of the bradykinin-forming cascade in mast cell dependent anaphylactic reactions as a potential mediator of severe hypotension, or airway compromise (asthma, laryngeal edema). We also consider airway obstruction due to inhibition of angiotensin converting enzyme with a diminished rate of endogenous bradykinin metabolism, leading not only to laryngeal edema, but massive tongue swelling with aspiration of secretions.

Wheat-dependent exercise-induced anaphylaxis (WDEIA) is one of the most severe forms of wheat allergy. It occurs in patients when they exercise after ingesting wheat-containing foods. Nowadays, the only possible alternative for WDEIA patients is to avoid such foods. This study investigated the potential of six RNA of interference (RNAi) wheat lines with low-prolamin content as alternatives for WDEIA patients. For that purpose, a high performance-liquid chromatography (HPLC) analysis was performed to evaluate differences in gluten protein fractions among these lines. Next, western blots were conducted to measure the immunoglobulin E (IgE) reactivity to wheat proteins in sera from five WDEIA patients. Additionally, monoclonal antibodies (moAb) recognition sites and the IgE binding sites were searched in all peptides identified by LC-MS/MS after protein digestion. The results showed a 61.4%–81.2% reduction in the gliadin content of the RNAi lines, accompanied by an increase in their high-molecular weight (HMW) glutenin content compared to the wild type bread wheat line (WT). In all cases, the reduction in gliadin content correlated with a decrease in IgE reactivity observed in the sera of WDEIA patients, highlighting the E82 and H320 lines. These two RNAi lines exhibited a ≤90% reduction in IgE reactivity. This reduction could be attributed to an absence of IgE binding sites associated with α- and ω5-gliadins, which were present in the WT. Overall, these lines offer a potential alternative for foodstuff for individuals with WDEIA.

Approximately 80% of the global cattle population is at risk of infestation and infection by ticks and tick-borne diseases (TTBDs). The economic losses from animal mortality, reduced production, vector control costs and animal treatment are very substantial, hence there is an urgent need to develop and deploy alternative vector control strategies. Breeding for host tick resistance has the potential for sustainable large-scale TTBD control especially in cattle. The gold standard method for phenotyping tick resistance in cattle is by counting ticks on the body but is very laborious and subjective. Better methods for phenotyping tick resistance more objectively, faster and at scale, are essential for selecting host genetic resistance to ticks. This study investigated the correlation between haematological cellular profiles and immunological responses (immunoglobulin E, IgE) and full body tick counts in herds of Bos indicus and Bos taurus following artificial tick challenge with Rhipicephalus decoloratus larvae. Fifty-four Friesian and Ayrshire (Bos taurus) and 52 East African Zebu (Bos indicus) calves were each infested with ∼2500 larvae. Near-replete adult female ticks (≥ 4.5 mm) were counted daily from Day 20–25. Blood and serum samples were obtained from each animal on Days 0 and 23 for cellular blood and IgE titre analysis, respectively. The indicine cattle were refractory to R. decoloratus infestation in comparison with the taurine breed (P

Wheat is a prominent allergenic food that can trigger life-threatening anaphylaxis. Presently, it remains unclear whether wheat glutenin (WG) extract possesses inherent sensitization potential independently, without the use of adjuvants, and whether it can sensitize mice to the extent of inducing life-threatening systemic anaphylaxis. In this study, we tested the hypothesis that repeated skin exposures to WG extract without adjuvant will sensitize mice with the resultant anaphylactic reaction upon systemic WG challenge. Balb/c mice were bred and maintained on a strict plant protein-free diet and were repeatedly exposed to a WG extract or vehicle once a week for 9 weeks. WG-specific (s)IgE and total (t)IgE levels were quantified. Mice were challenged with WG extract to induce anaphylactic reactions as measured by hypothermic shock response (HSR) and mucosal mast cell degranulation response (MMCR). We also conducted proteomic analysis of 120 spleen immune markers. These skin-sensitized mice exhibited exposure-dependent IgE responses and near-fatal anaphylaxis upon challenge. Proteomic analysis identified seven dramatically elevated immune biomarkers in anaphylactic mice. These data reveal that WG is intrinsically allergenic, and that chronic skin exposure to WG extract can prime the mice for potentially fatal anaphylaxis. [ABSTRACT FROM AUTHOR]

Background: Allergens from Fagales trees frequently cause spring allergy in Europe, North America, and some parts of Asia. The definition of the birch homologous group, which includes birch (Bet v), oak (Que a), alder (Aln g), hazel (Cor a), hornbeam (Car b), beech (Fag s), and chestnut (Cas s), is based on high allergen sequence identity and extensive IgE cross-reactivity. Clinical effect was seen during the alder/hazel, birch, and oak pollen seasons after treatment with tree SLIT-tablets containing only birch allergen extract. Here, we characterize Tcell reactivity with respect to epitope specificities and cross-reactivity toward various Bet v 1 family members, (PR-10/group 1 major allergens). This crossreactivity may be part of the immunological basis of clinical effect or crossprotection when exposed to birch homologous tree species. Method: T-cell lines were generated from 29 birch-allergic individuals through stimulation of peripheral blood mononuclear cells (PBMCs) with birch/Bet v or oak/Que a allergen extracts. T-cell responses to allergen extracts, purified group 1 allergens, and overlapping 20-mer peptides (Bet v 1, Aln g 1, Cor a 1, and Que a 1) were investigated by T-cell proliferation and cytokine production. Crossreactivity was evaluated based on Pearson’s correlations of response strength and further investigated by flow cytometry using tetramer staining for homologous peptide pairs. Results: T-cell reactivity toward extracts and group 1 allergens from across the birch homologous group was observed for birch/Bet v as well as oak/Que a Tcell lines. T-cell lines responded to multiple Bet v 1 homologous peptides from Aln g 1 and Cor a 1 and a subset of Que a 1 peptides. Significant Pearson’s correlations between frequently recognized peptides derived from Bet v 1 and the corresponding peptides derived from alder, hazel, and oak strongly supported the T-cell cross-reactivity toward these allergens. Cross-reactivity between birch and birch homologous peptides was confirmed by pMHCII tetramer staining. Conclusion: T cells from birch tree pollen allergic individuals respond to multiple trees within the birch homologous group in accordance with the level of sequence homology between Bet v 1 family members, (PR-10 allergens) from these allergen sources, confirming the basis for clinical cross-protection. [ABSTRACT FROM AUTHOR]

Simple Summary: It has long been known that antibodies of a certain class, called IgE, are the main cause of allergic reactions to food. Other antibody types such as IgA and IgG can suppress the allergic reaction. Even IgE, which binds the allergen only weakly (i.e., with low affinity), seems to have a protective effect. This review discusses the role of distinct antibody types in food allergy, and the underlying mechanisms of action. These findings might be important to understand the development and course of food allergies, and could help to improve diagnostics and therapy. Food allergies are a growing public health concern worldwide, especially in children and young adults. Allergen-specific IgE plays a central role in the pathogenesis of food allergies, but their titers poorly correlate with allergy development. Host immune systems yield allergen-specific immunoglobulin (Ig)A, IgE and IgG subclasses with low or high affinities and differential Fc N-glycosylation patterns that can affect the allergic reaction to food in multiple ways. High-affinity IgE is required to induce strong mast cell activation eventually leading to allergic anaphylaxis, while low-affinity IgE can even inhibit the development of clinically relevant allergic symptoms. IgA and IgG antibodies can inhibit IgE-mediated mast cell activation through various mechanisms, thereby protecting IgE-positive individuals from allergy development. The production of IgE and IgG with differential allergenic potential seems to be affected by the signaling strength of individual B cell receptors, and by cytokines from T cells. This review provides an overview of the diversity of the B cell response and the diverse roles of antibodies in food allergy. [ABSTRACT FROM AUTHOR]

We have previously produced a toolkit of antibodies, comprising recombinant human antibodies of all but one of the human isotypes, directed against the polcalcin family antigen Phl p 7. In this work, we complete the toolkit of human antibody isotypes with the IgD version of the anti-Phl p 7 monoclonal antibody. We also raised a set of nanobodies against the IgD anti-Phl p 7 antibody and identify and characterize one paratope-specific nanobody. This nanobody also binds to the IgE isotype of this antibody, which shares the same idiotype, and orthosterically inhibits the interaction with Phl p 7. The 2.1 Å resolution X-ray crystal structure of the nanobody in complex with the IgD Fab is described. [ABSTRACT FROM AUTHOR]

This review is devoted to the analysis of the main mechanisms of the formation of IgE-producing cells in the body and a brief review of the main, most striking candidate agents for use in innovative methods of therapy for IgE-dependent pathologies. Data are presented according to which the role of IgE+ plasma cells and various subpopulations of memory B-lymphocytes in the formation and persistence of the state of sensitization to a harmless allergen differs depending on the model system used or the clinical case under study. Therefore, drugs that target signaling pathways involved in the regulation of both plasma cells and memory B-lymphocytes are especially promising in the treatment of allergic diseases. The authors conclude that the components of the cellular response to oxidative stress and related genotoxic stress and ER stress are the most promising as such targets, since (a) all of them directly or indirectly affect the processes that regulate both of these subpopulations; (b) are involved in the process of formation and maintenance of local allergic inflammation. The review presents data pointing to the particular promise of using nanoparticles of noble metals and complexes of rare earth metals of lanthanides in this regard, due to their ability to induce long-term effects in small doses due to changes in the properties of innate immunity cells and long-term accumulation in the body. [ABSTRACT FROM AUTHOR]

Background: Hymenoptera envenomation with honey bee (Apis mellifera) and paper wasp (Polistes spp.) may cause life‐threatening anaphylaxis in dogs. In human patients, clinical history, intradermal testing (IDT) and measurement of allergen‐specific serological immunoglobulin (Ig)E (sIgE) are used to support a diagnosis of Hymenoptera venom hypersensitivity. The utility of venom allergen‐specific sIgE has not yet been evaluated for this purpose in dogs. Objectives: The objective of the study was to investigate the sensitivity (sn), specificity (sp) and positive predictive value (PPV) of honey bee and paper wasp serological titres using a commercially available sIgE assay [VARL (Veterinary Allergen Reference Laboratory) Liquid Gold] against clinical history for a diagnosis of Hymenoptera hypersensitivity in dogs. Materials and Methods: Honeybee and paper wasp IgE serum titres were measured in 15 client‐owned dogs with a diagnosis of Hymenoptera venom hypersensitivity based on a history of anaphylaxis, owner observation of Hymenoptera, and positive IDT to bee and/or wasp; and in 10 client‐owned dogs with no known history of anaphylaxis or Hymenoptera exposure and a negative IDT to bee and wasp. Results: Analysis of receiver operating characteristic (ROC) curves demonstrate that a VARL score cut‐off of one of six for honeybee yields Sn, Sp and PPV of 40%, 60% and 60%, respectively, and two of six for wasp yields Sn, Sp and PPV of 25%, 78% and 60%, respectively. Conclusions and Clinical Relevance: Owing to the poor sensitivity and PPV of sIgE assays for both bee and wasp hypersensitivity in dogs with known envenomation and anaphylaxis, the use of sIgE cannot be recommended as a tool for venom identification. [ABSTRACT FROM AUTHOR]

Vermicompost tea (VCT) is the effluent or leachate with a honeybrown colour collected during vermicomposting, an ecologically significant process essential to today's organic and regenerative agriculture. Dried earthworm, a.k.a. dilong (DL, meaning "earth dragon") in traditional Chinese herbal medicine, has long been used as a key component to treat diverse skin diseases, including eczema. In the present study, we hypothesized that VCT might have a positive influence on eczema therapy. It was found that the oral application of 50% VCT in mouse model reduced the ear allergic scores and alleviated the histological changes caused by eczema. Furthermore, the levels of Th2-associated and pro-inflammatory cytokines (namely IL-4 and IL-13 in serum) and IgE (in serum and ear tissues) were significantly reduced by VCT. Therefore, oral administration of 50% VCT exerts immunomodulatory effects on the development of eczema, suggesting its potential as a nutraceutical candidate for eczema treatment. [ABSTRACT FROM AUTHOR]

Follicular regulatory T (Tfr) cells play various roles in immune responses, contributing to both positive and negative regulation of foreign antigen-specific B cell responses, control over autoreactive antibody responses and autoimmunity, and B cell class-switching to IgE and allergy development. Studies conducted on mice uncovered various subsets of CXCR5+FoxP3+CD4+ Tfr cells that could differently contribute to immune regulation. Moreover, recent studies of human Tfr cells revealed similar complexity with various subsets of follicular T cells of different origins and immunosuppressive and/or immunostimulatory characteristics. In this review we will overview and compare Tfr subsets currently identified in mice and humans and will discuss their origins and antigen specificity, as well as potential modes of action and contribution to the control of the autoimmune and allergic reactions. [ABSTRACT FROM AUTHOR]

The hyper-immunoglobulin E syndrome (HIES) is a primary immunodeficiency disease originally described as Job syndrome. The fundamental causative variant of the HIES is an autosomal dominant mutation in the signal transducer and activator of transcription 3 (STAT3) gene. It is characterized by recurrent staphylococcal cold skin abscess, sinopulmonary infection, eczema, head and face anomalies, frequent bone fractures, eosinophilia and extremely high serum IgE levels (IgE ≥ 2000 IU/mL). However, multiple other genetic defects are also known as HIES-like disorders. Apart from infectious manifestations, STAT3, DOCK8 and TYK2 gene mutations are associated with various malignancies. The most common malignancies reported in these patients are lymphomas, including Hodgkin's and non-Hodgkin's lymphomas (NHL) of B and T cells. This systematic review aimed to investigate the prevalence of malignancies in HIES and the factors associated with malignancy in these patients. In this survey, all articles published until April 1st, 2023, in Scopus, PubMed and Web of Science databases based on three groups of keywords related to HIES syndrome and malignancy were reviewed by three different researchers. Finally, 26 articles were evaluated from which 24 papers were meta-analyzed. In the current study, the demographic information of 1133 patients with HIES, which was mentioned in 24 articles enrolled in the project, was collected, and the information related to patients who had malignancy was analyzed and meta-analyzed. A total of 96 patients out of 1133 studied patients had at least one type of malignancy, the overall prevalence of malignancies reported in the articles was 6.5% (95% confidence interval 4.1–9%), and the total prevalence of malignancy in patients with NHL type and patients with squamous cell carcinoma (SCC) was 2.9% (95% confidence interval 1.7–4.4%) and 2.2% (95% confidence interval 0.3–4.1%), respectively. The results of this study indicated that in 6.5% of cases, HIES was complicated with malignancy, and considering the higher rate of these malignancies in women as well as in DOCK8 mutation sufferers, it is necessary for physicians to be aware of this association and includes malignancy screening in follow-up and periodic examinations of these patients. Indeed, more studies in this field will help to clarify the precise figures and predisposing factors of the relationship between HIES and malignancy. [ABSTRACT FROM AUTHOR]

A total of 50 serum samples were collected from patients with Echinococcus granulosus and 38 serum samples from healthy humans were taken from the Al-Furat AL-Awsat Hospital, Maternity and Children Teaching Hospital and Al-Diwaniyah Teaching Hospital in Al-Diwaniyah and from Specialized Hospital for Gastroenterology and Hepatology in AL-Najaf for the period from November 2022 to April 2023. The test was performed on 5 ml of venous blood, which was collected from each sample for an Enzyme-linked immunosorbent assay (ELISA) test to detect Echinococcosis IgE. The Distribution of Hydatid Cysts according to the site of the infection was the high rate of infection in the liver compared with other organs. The concentration level of IgE was increased in patients compared with the control, with a significant difference at (P ≤ 0.05) while the level of IgE was decreased after the surgery compared with the before the surgery in patients with a significant difference at (P ≤ 0.05). The levels of IgE concentrations in patients according to the location of the cyst were the highest level in the liver. [ABSTRACT FROM AUTHOR]

The current study was conducted to measure some immunoglobulin IgE, IgG, IgM, some interleukins interleukin 4 (IL-4), interleukin 5 (IL-5) and a complete blood count (CBC) in patients suffering from hypersensitivity type 1 (drug allergy, and asthma). The study began from 1/9/2022 to 1/3/2023 and included 59 people of all ages. The current results showed that people with drug allergy and asthma had an increase in the concentration of IL-4 (407.8 ±27.0), (837.6 ± 29.4), IL-5 (323.1 ±39.7) (568.4 ± 32.1) respectively. The level of IgE, IgG and IgM was elevated in patients suffering from drug allergies (11.2±2.6) (18.1±2.8) (and 47.9±5.3) respectively and asthma was (30.3±3.4), (26.1 ± 4.6) and (50.2 ± 8.6) respectively. The results of the complete blood count showed a significant increase in the white blood cells, Eosinphile. In addition to many differences in blood parameters compared to normal proportions. It was also found that the IgE concentration decreased with age, while the IgG antibody concentration increased compared to the standard sample and with the increase in age groups. [ABSTRACT FROM AUTHOR]

The existence of long‐lived IgE antibody‐secreting cells (ASC) is contentious, with the maintenance of sensitization by the continuous differentiation of short‐lived IgE+ ASC a possibility. Here, we review the epidemiological profile of IgE production, and give an overview of recent discoveries made on the mechanisms regulating IgE production from mouse models. Together, these data suggest that for most individuals, in most IgE‐associated diseases, IgE+ ASC are largely short‐lived cells. A subpopulation of IgE+ ASC in humans is likely to survive for tens of months, although due to autonomous IgE B cell receptor (BCR) signaling and antigen‐driven IgE+ ASC apoptosis, in general IgE+ ASC probably do not persist for the decades that other ASC are inferred to do. We also report on recently identified memory B cell transcriptional subtypes that are the likely source of IgE in ongoing responses, highlighting the probable importance of IL‐4Rα in their regulation. We suggest the field should look at dupilumab and other drugs that prohibit IgE+ ASC production as being effective treatments for IgE‐mediated aspects of disease in most individuals. [ABSTRACT FROM AUTHOR]

Phosphoinositide 3‐kinase (PI3K) p110δ signalling negatively regulates the production of mouse IgE. However, there are disparities between the mouse and human IgE biology, and the role of PI3K p110δ in the production of human IgE is yet to be determined. To investigate the effect of PI3K p110δ inhibition in the production of human IgE we isolated human B cells from tonsil tissue and stimulated them with IL‐4 and anti‐CD40 antibody to induce class switching to IgE and IgG1 in the presence or absence of IC87114, a small molecule inhibitor of PI3K p110δ. Using FACS, RT‐PCR and ELISA we examined the effect of PI3K p110δ inhibition on IgE production and determined the mechanisms involved. Unlike in mice, we observed that PI3K p110δ inhibition significantly reduces the number of IgE+ switched cells and the amounts of secreted IgE in IL4 and anti‐CD40 cultures. However, the number of IgG1+ cells and secreted IgG1 were largely unaffected by PI3K p110δ inhibition. The expression levels of AID, ε and γ1 germinal transcripts or other factors involved in the regulation of CSR to IgE and IgG1 were also unaffected by IC87114. However, we found that IC87114 significantly decreases the proliferation of tonsil B cells stimulated with IL‐4 and anti‐CD40, specifically reducing the frequency of cells that had undergone 4 divisions or more. In addition, PI3K p110δ inhibition reduced the levels of IRF4 expression in IgE+ germinal centre‐like B cells leading to a block in plasma cell differentiation. In conclusion, PI3K p110δ signalling is required for the production of human IgE, which makes it a pharmacological target for the treatment of allergic disease. [ABSTRACT FROM AUTHOR]

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It has recently been argued that the intergenerational income elasticity (IGE) ubiquitously estimated in the economic mobility literature should be replaced by the IGE of expected income. This article advances a generalized error-in-variables model for the estimation of the latter IGE with short-run proxy measures of income and the Poisson pseudo-maximum likelihood estimator of constant elasticities. Empirical analyses with data from the panel study of income dynamics offer clear support for the account of lifecycle and attenuation biases the model provides. Together, the model and the associated empirical evidence supply a methodological justification for the estimation of the IGE of the expectation with proxy income variables that satisfy some conditions. This eliminates the main obstacle for making this IGE the workhorse elasticity of the economic mobility field, which would in turn dissolve the selection bias problem generated by the current expedient of dropping children with zero income from samples in order to make estimation of the conventional IGE possible. [ABSTRACT FROM AUTHOR]

Fruit allergies manifest with a diverse array of clinical presentations, ranging from localized contact allergies and oral allergy syndrome to the potential for severe systemic reactions including anaphylaxis. The scope of population-level prevalence studies remains limited, largely derived from single-center or hospital-based investigations. In this comprehensive review, we conducted a systematic literature search spanning the years 2009 to 2023, with full acknowledgment of potential analytical biases, to provide a global overview of fruit allergy prevalence. The primary mechanistic underpinning of fruit allergies stems from cross-reactivity between aeroallergens and food allergens, a consequence of structurally similar epitopes—a phenomenon recognized as pollen food allergy syndrome (PFAS). In the era of molecular allergology, numerous studies have dissected allergen components with substantial clinical relevance. Within this review, we explore important allergenic molecules found in plant-based foods, scrutinize pertinent cross-reactivity patterns, and offer insights into management recommendations. Additionally, we compare guideline recommendations to enhance clinical understanding and inform decision making. [ABSTRACT FROM AUTHOR]

Background: Allergic bronchopulmonary aspergillosis (ABPA) develops in the presence or absence of asthma, either atopic or nonatopic. We have tried to explore the essential components in the pathogenesis of the disease, which are either consistent and variable according to the presence and type of asthma. Methods: Non‐cystic fibrosis ABPA cases satisfying Asano's criteria were extracted from a prospective registry of ABPA and related diseases in Japan between 2013 and 2023. According to the type of preceding asthma, ABPA was classified into three groups: ABPA sans asthma (no preceding asthma), ABPA with atopic asthma, and ABPA with nonatopic asthma. Exploratory and confirmatory factor analyses were performed to identify the components that determined the clinical characteristics of ABPA. Results: Among 106 cases of ABPA, 25 patients (24%) had ABPA sans asthma, whereas 57 (54%) and 24 (23%) had ABPA with atopic and nonatopic asthma, respectively. Factor analysis identified three components: allergic, eosinophilic, and fungal. Patients with atopic asthma showed the highest scores for the allergic component (p <.001), defined by total and allergen‐specific IgE titers and lung opacities, and the lowest scores for the fungal component defined by the presence of specific precipitin/IgG or positive culture for A. fumigatus. Eosinophilic components, including peripheral blood eosinophil counts and presence of mucus plugs/high attenuation mucus in the bronchi, were consistent among the three groups. Conclusion: The eosinophilic component of ABPA is considered as the cardinal feature of ABPA regardless of the presence of preceding asthma or atopic predisposition. [ABSTRACT FROM AUTHOR]

Background: Chronic actinic dermatitis (CAD) is an immune‐mediated photodermatosis characterized by a high eosinophil count and total immunoglobulin E (IgE) in the peripheral blood of patients. At present, however, the reasons for their elevation remain unclear. Objective: The current study aimed to detect changes in inflammatory cytokines in CAD and explore their role in this disease. Methods: Enzyme‐linked immunosorbent assay and Luminex assay were conducted to measure inflammatory factor levels. Immunohistochemical analysis and quantitative real‐time polymerase chain reaction were performed to evaluate the expression levels of interleukin‐36γ (IL‐36γ), IL‐8, chemokine (C‐C motif) ligand 17 (CCL17), and CCL18. CCK8 kits were used to assess cell proliferation. Immunofluorescence was used to detect nuclear factor κB (NF‐κB) p65 nuclear translocation. Western blot analysis was performed to detect the protein expression level of phosphorylated NF‐κB (p‐NF‐κB) p65. Hematoxylin and eosin and Masson trichrome staining were applied to observe histological changes in a chronic photo‐damaged mouse model. Results: Eosinophils, total IgE, IL‐36γ, IL‐8, tumor necrosis factor α, CCL17, and CCL18 were elevated in CAD. Of note, IL‐36γ promoted the proliferation of eosinophilic cells (EOL‐1) and the production of IgE in peripheral blood mononuclear cells. IL‐36γ also promoted the production of IL‐8 and CCL18 in immortalized human keratinocytes (HaCaT cells), while ultraviolet radiation (UVR)‐induced IL‐36γ via activation of the NF‐κB signaling pathway. Conclusions: IL‐36γ was involved in the pathogenesis of CAD and UVR contributed to the production of IL‐36γ, which may provide a novel therapeutic target for CAD. [ABSTRACT FROM AUTHOR]

Chronic spontaneous urticaria (CSU) is a debilitating inflammatory disorder of the skin, characterized by a fluctuating natural history, a complex mechanism of action, and a significant burden on patients, including effect on quality of life, development of psychosocial disorders, and a range of comorbidities. Recent international guidelines recommend a therapeutic approach of first-line treatment with second generation H1-antihistamines and second-line treatment with the biologic omalizumab. Here, the salient aspects of CSU and current status of data for omalizumab for patients with CSU are reviewed, with a focus on mechanism of action, efficacy and real-world effectiveness (including patient outcomes, response, relapse, and remission), and safety (including consideration of the risk of anaphylaxis). The review also considers recent data on COVID-19, CSU, and omalizumab and presents our perspective on future needs. Overall, the data suggest that omalizumab is an effective and well-tolerated treatment for patients with CSU that provides benefits for a wide range of patients. Plain Language Summary: Chronic spontaneous urticaria is a skin condition that causes raised red itchy bumps (known as hives) that appear on the skin on most days for 6 weeks or longer. The hives may be big or small, may be warm to touch, may come and go, and may affect a person's quality of life. Omalizumab is a treatment for people living with chronic spontaneous urticaria that can stop the appearance of hives. This article summarizes all the information that we know about omalizumab for chronic spontaneous urticaria, such as how it works, how successful it is at improving hives, how long it takes to work, how it makes patients feel, and how safe it is. The information in this article shows that omalizumab is helpful for many people with chronic spontaneous urticaria. [ABSTRACT FROM AUTHOR]

Background: We have identified and reported a novel antigen, nonprotein‐specific secreted EP1‐like glycoprotein (51 kDa), for lettuce‐related respiratory allergy. Objective: We aimed to identify a novel antigen for lettuce‐related respiratory allergy that is different from epidermis‐specific secreted EP1‐like glycoprotein. Methods: Immunoblotting was performed using an immunoglobulin E‐specific antibody. The antigen‐antibody reaction was confirmed by means of enzyme‐linked immunosorbent assaying. LC‒MS/MS analysis was carried out to detect a novel protein found in sera from 3 of 13 patients with lettuce‐related respiratory allergy. Finally, we purified a novel protein from Escherichia coli. Results: Immunoblotting assays showed common bands of 17 kDa in the sera of 3 of 13 patients. An enzyme‐linked immunosorbent assay confirmed that the patient sera reacted with lettuce latex juice. A 17 kDa protein band that showed antigenic reactivity in 3 of 13 patient sera was identified as a kirola‐like protein by LC‒MS/MS. In addition, although we purified this protein, we failed to show the inhibitory effect. Conclusion: A 17 kDa protein that is a potentially novel antigen of lettuce‐associated respiratory allergy was identified. In further studies, we will focus on purifying this novel protein to diagnose lettuce allergy. Key message: Immunoblotting analysis showed common bands at 17 kDa for lettuce latex and patient serum.The 17 kDa protein bands were identified as kirola‐like protein by LC‒MS/MS.We purified the kirola‐like protein. [ABSTRACT FROM AUTHOR]

This article discusses a study conducted in Sweden that aimed to investigate the association between the gut microbiome and allergic asthma in a cohort of twin children aged 9 to 14. The study found no evidence of differences in the overall gut microbial richness or composition between healthy controls and children diagnosed with allergic asthma, asthma only, or IgE sensitization only. The combined activity of raised IgE and asthma on the differential abundance in allergic asthma was almost exclusively additive, with no systematic evidence for synergistic or antagonistic effects. The study provides valuable insights into the role of the gut microbiome in asthma and contributes to the understanding of allergic diseases. [Extracted from the article]

IgE sensitization profiles to single birch allergens in birch-sensitized patients differ among European countries. The aim of this study was to determine the distribution of specific IgE antibodies to major and minor birch pollen allergens in a population of allergic Norwegian individuals by using a birch allergic blood donor population as a surrogate sample. Sixty blood donors were recruited and sampled based on birch allergy symptoms such as rhinitis, rhinoconjunctivitis and/or mild asthma in previous seasons. All sera were collected before start of the pollen season and tested using a line blot assay (Euroimmun AG, Lübeck, Germany) for IgE to birch and timothy pollen. Both extracts, single allergens, and cross-reacting carbohydrate determinants (CCD) were analysed. Only donors with specific IgE to birch and/or timothy grass were further evaluated. Specific IgE to birch pollen extract was found in 52 sera, and sensitization to timothy grass in 40 sera. Specific IgE to Bet v 1 was predominant in contrast to Bet v 4 which was absent. However, sensitization to the minor allergens Bet v 2 and 6 was always found together with high levels of IgE to Bet v 1. Subjects sensitized to the profilin Bet v 2 from birch were also sensitized to Phl p 12 from timothy grass. In conclusion, there was predominantly Bet v 1 sensitization in this cohort and low sensitization to minor allergens and cross-reactive allergens (Bet v 2, Bet v 4, Phl p 7 and Phl p 12). [ABSTRACT FROM AUTHOR]

This chapter examines how innovative and emerging food processing technologies, such as those that use heat, electricity, electromagnetic waves, and pressure, can modify protein denaturation, aggregation, and intermolecular interactions pathways, which can result in varying immunoreactive responses. It emphasizes the need to understand how these processing methods affect the protein epitopes recognized by antibodies and their respective priming pathways, especially during the sensitization stage that precedes an allergic response. Although traditional processing methods have been investigated, the impact of novel technologies on food protein allergenicity remains largely unknown. The chapter specifically focuses on milk proteins, which have clinical significance and are associated with cow's milk allergy, one of the most common food allergies in young children. Additionally, it examines potential scientific advancements that novel processing methods may bring to this field. [ABSTRACT FROM AUTHOR]

Background: Evidence has shown that glucocorticoid-induced transcript 1 (GLCCI1) single nucleotide polymorphism (SNP) rs37937 is associated with asthma. Objectives: The objective of this study was to investigate whether the GLCCI1 SNP rs37937 is a risk factor for allergic rhinitis (AR) in a Chinese Han population. Methods: A total of 220 individuals including 109 AR patients and 111 healthy subjects were included. The genotyping of GLCCI1 rs37973 was performed by the SNaPshot method. The correlations of rs37973 polymorphism, AR risk, and clinical characteristics were further analyzed, as well as the treatment response to intranasal corticosteroids (INCS) in AR patients of different genotypes. Results: Three GLCCI1 rs37973 SNP genotypes were identified in both AR patients and healthy subjects. Significant association between rs37973 polymorphism and AR under allele model, dominant model, heterozygote model, and homozygote model were shown. The A allele frequency of SNP rs37973 in AR was significantly higher than that in controls. The serum total immunoglobulin E (IgE) in AR patients of AA genotype was significantly higher than in patients of GA and GG genotype, and the serum total IgE in GA genotype was significantly higher than in GG genotype. Interestingly, after 4 weeks of INCS treatment for AR patients, the improvement of the nasal itching score, sneezing score, runny nose score, total nasal symptom score, and visual analog scale score of the GG genotype were worse than the AA or GA genotype. Conclusion: The GLCCI1 rs37937 polymorphism is associated with the risk of developing AR and the response to INCS treatment in the Chinese Han population. [ABSTRACT FROM AUTHOR]

Food-dependent exercise-induced allergic reactions (FDEIA) represent a distinct clinical phenomenon where symptoms arise during exercise following the consumption of specific trigger foods, with the most severe manifestation being anaphylaxis—a condition distinct from typical exercise-induced or food-induced anaphylaxis. In FDEIA, patients can either exercise or tolerate specific foods separately without experiencing any allergic reactions. Diagnosis relies on patient history and provocation testing, requiring rigorous implementation within a supervised hospital environment. Positive symptoms and clinical signs during testing confirm FDEIA, while negative outcomes do not preclude its presence. Exercise stands as the primary trigger, followed by nonsteroidal anti-inflammatory drugs (NSAIDs) and alcohol. The utilization of various protocols for food cofactor challenges to confirm FDEIA yields differing diagnostic outcomes. We highlight the updated concept of food cofactor challenges, incorporating protocols reported in the literature, and summarize current recommendations and comprehensive management approaches for FDEIA patients. [ABSTRACT FROM AUTHOR]

Background: Hitherto, the bulk of diagnostic criteria regards Aspergillus-specific immunoglobulin E as a key item, and regard IgG as an auxiliary method in diagnose. Nevertheless, there is no conclusive study in summarize the performance of IgG and IgE diagnosing ABPA. Methods: We conducted a systematic review to identify studies report results of IgE and IgG detection in diagnosing ABPA. QUADAS-2 tool was used to evaluate included studies, and we applied the HSROC model to calculate the pooled sensitivity and specificity. Deeks' funnel was derived to evaluated the public bias of included studies, and Cochrane Q test and I2 statistic were used to test the heterogeneity. Results: Eleven studies were included in this study (1127 subjects and 215 for IgE and IgG). Deeks's test for IgE and IgG were 0.10 and 0.19. The pooled sensitivity and specificity for IgE were 0.83 (95%CI: 0.77, 0.90) and 0.89 (0.83, 0.94), and for IgG were 0.93 (0.87, 0.97) and 0.73 (0.62,0.82), with P value < 0.001. The PLR and NLR for IgE were 7.80 (5.03,12.10) and 0.19 (0.13,0.27), while for IgG were 3.45 (2.40,4.96) and 0.09 (0.05,0.17). The combined diagnostic odds ratio and diagnostic score were 41.49 (26.74,64.36) and3.73 (3.29,4.16) for IgE, respectively, and were 38.42 (19.23,76.79) and 3.65 (2.96,4.34) for IgG. Conclusion: The sensitivity for IgG diagnosing ABPA is higher than IgE, while the specificity for IgE is higher. IgG might be able to play a more important role in filtering ABPA patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Helminth infections may have different effects on human health, including risk or protection from other diseases. Ascariasis (caused by Ascaris lumbricoides), the most common soil-transmitted helminthiasis, can induce allergic responses, and also immunosuppression. During ascariasis, antibodies for many A. lumbricoides antigens are produced; however, there is no clear information about the concurrent IgE, IgG4 and IgG production as well as their influences on the actual allergic reactions. In this study, we evaluated antibody responses to two A. lumbricoides molecules, rAsc l 5 and rAl-CPI (an anti-inflammatory product), in an A. lumbricoides endemic population and explored their relationship with the infection and asthma. Our results show that both molecules induce specific antibodies, but, in contrast to rAl-CPI, rAsc l 5 activates cells associated with allergic reactions in some individuals. All together, these data suggest that these molecules have differences in the elicited immune response. Immunity to Ascaris lumbricoides influences the pathogenesis of allergic diseases. Antibody responses to its proteins have been found to be associated with asthma presentation; however, helminth products that induce immunosuppression have been reported, which also raise specific antibodies. We aimed to evaluate antibody responses (IgE, IgG4 and IgG) to two A. lumbricoides molecules, Asc l 5 and Al-CPI (an anti-inflammatory Cysteine Protease Inhibitor), in an endemic population, exploring their relationships with the infection and asthma. The two molecules were produced as recombinant proteins in E. coli expression systems. Specific antibodies were detected by ELISA. Lower human IgE, but higher IgG4 and IgG antibody levels were observed for Al-CPI than for rAsc l 5. The IgE/IgG4 isotype ratio was significantly higher for Asc l 5 than for Al-CPI. In humans Al-CPI did not induce basophil activation as has been previously described for Asc l 5. In mice, Al-CPI induced fewer IgE responses, but more IgG2a antibody titers than rAsc l 5. Our results suggest that these molecules elicit different patterns of immune response to A. lumbricoides. [ABSTRACT FROM AUTHOR]

Introduction: Allergen immunotherapy (AIT) is an effective therapy for allergic rhinitis and may have long-term benefits. However, these benefits have not been strictly defined for older people. Aim: The evaluation of the effectiveness of AIT in patients over 60 with allergic rhinitis and house dust mites (HDM) allergy over a period of 7 years was performed. Material and methods: Patients after three years of HDM-AIT were observed to assess the sustained clinical effect of treatment. The average adjusted symptom score (AAdSS) and sIgG4 were monitored for 7 years after sublingual (SLIT) and injection AIT (SCIT). Results: After 3 years of HDM-AIT, a significant clinical effect was observed in the group after SLIT and SCIT based on AAdSS compared to the baseline and the placebo group (p < 0.05). After 7 years of follow-up, there was a sustained trend of decrease in clinical symptoms in desensitized patients relative to placebo. Serum sIgG4 was constantly present in all desensitized patients. Conclusions: AIT may be beneficial for treating seniors with allergic rhinitis and allergies to house dust mites. [ABSTRACT FROM AUTHOR]

Background: The domestic mite Blomia tropicalis is a major source of allergens in tropical and subtropical regions. Despite its great medical importance, the allergome of this mite has not been sufficiently studied. Only 14 allergen groups have been identified in B. tropicalis thus far, even though early radioimmunoelectrophoresis techniques (27 uncharacterized allergen complexes) and comparative data based on 40 allergen groups officially recognized by the World Health Organization (WHO)/IUIS in domestic astigmatid mites suggest the presence of a large set of additional allergens. Methods: Here, we employ a multiomics approach to assess the allergome of B. tropicalis using genomic and transcriptomic sequence data and perform highly sensitive protein abundance quantification. Findings: Among the 14 known allergen groups, we confirmed 13 (one WHO/IUIS allergen, Blo t 19, was not found) and identified 16 potentially novel allergens based on sequence similarity. These data indicate that B. tropicalis shares 27 known/deduced allergen groups with pyroglyphid house dust mites (genus Dermatophagoides). Among these groups, five allergen‐encoding genes are highly expressed at the transcript level: Blo t 1, Blo t 5, Blo t 21 (known), Blo t 15, and Blo t 18 (predicted). However, at the protein level, a different set of most abundant allergens was found: Blo t 2, 10, 11, 20 and 21 (mite bodies) or Blo t 3, 4, 6 and predicted Blo t 13, 14 and 36 (mite feces). Interpretation: We report the use of an integrated omics method to identify and predict an array of mite allergens and advanced, label‐free proteomics to determine allergen protein abundance. Our research identifies a large set of novel putative allergens and shows that the expression levels of allergen‐encoding genes may not be strictly correlated with the actual allergenic protein abundance in mite bodies. [ABSTRACT FROM AUTHOR]

Background: Grass leaf has been suspected of causing immunoglobulin (Ig)E‐mediated immediate hypersensitivity reactions in humans and dogs. However, most studies in this area are case‐control studies without in vitro data showing the involvement of IgE in the reaction. Laboratory studies have demonstrated the reactivity to a 50–55 kDa protein with clinical signs immediately after contact with grass leaf material. The clinical findings of dogs with atopic‐like dermatitis immediately after contact with grass leaf material suggest the involvement of grass leaves as the allergen source. Objectives: This study was designed to test the IgE‐reactivity of grass leaf proteins in dogs with clinical signs and positive scratch test results against grass leaf material. Materials and Methods: The serum of 41 patients with a history of allergy and suspected to grass leaf material was immunoblotted against grass leaf extracts from five suspected grass species. The IgE‐positive blots were separated with 2D gel electrophoresis and analysed with mass spectrometry (MS). Commercially supplied proteins were used to validate immunoblot activity. Results: The serum of 25 dogs diagnosed with grass dermatitis had positive IgE‐specific immunoblot against one or more grass leaf extracts. The MS data indicated a reactive band at 55 kDa to be beta‐amylase or RuBisCO (ribulose‐1,5‐bisphosphate carboxylase/oxygenase) large subunit (RbLS). All tested dog sera showed IgE‐reactivity with beta‐amylase and some with RbLS. Conclusions and Clinical Relevance: Canines with clinical signs of grass‐related dermatitis had IgE‐reactivity against grass leaf proteins. Serum IgE‐reactivity to beta‐amylase and RuBisCO large subunit may indicate that these proteins act as allergens, possibly causing pruritus and skin lesions. [ABSTRACT FROM AUTHOR]

Objectives Recently, the involvement of basophils and IgE-type autoantibodies in the pathogenesis of SLE has been elucidated using mouse models; however, few studies have been conducted in humans. In this study, the role of basophils and anti-double-stranded DNA (dsDNA) IgE in SLE was examined using human samples. Methods The correlation between disease activity and serum levels of anti-dsDNA IgE in SLE was evaluated using enzyme-linked immunosorbent assay. Cytokines produced by IgE-stimulated basophils from healthy subjects were assessed using RNA sequences. The interaction of basophils and B cells to promote B cell differentiation was investigated using a co-culture system. The ability of basophils from patients with SLE with anti-dsDNA IgE to create cytokines that may be involved in B cell differentiation in response to dsDNA was examined using real-time PCR. Results Anti-dsDNA IgE levels in the serum of patients with SLE correlated with disease activity. Healthy donor basophils produced IL-3, IL-4 and TGF-β1 after anti-IgE stimulation. Co-culture of B cells with anti-IgE-stimulated basophils increased plasmablasts which were cancelled by neutralizing IL-4. After encountering the antigen, basophils released IL-4 more quickly than follicular helper T cells. Basophils isolated from patients with anti-dsDNA IgE promoted IL-4 expression by adding dsDNA. Conclusions These results suggest that basophils contribute to the pathogenesis of SLE by promoting B cell differentiation via dsDNA-specific IgE in patients similar to the process described in mouse models. [ABSTRACT FROM AUTHOR]

Poorly controlled asthma is especially common in low resource countries. Aside from lack of access to, or poor technique with, inhaled beta-2 agonists and corticosteroids, the most problematic forms of asthma are frequently associated with both fungal allergy and exposure, especially in adults leading to more asthma exacerbations and worse asthma. The umbrella term 'fungal asthma' describes many disorders linked to fungal exposure and/or allergy to fungi. One fungal asthma endotype, ABPA, is usually marked by a very high IgE and its differential diagnosis is reviewed. Both ABPA and fungal bronchitis in bronchiectasis are marked by thick excess airway mucus production. Dermatophyte skin infection can worsen asthma and eradication of the skin infection improves asthma. Exposure to fungi in the workplace, home and schools, often in damp or water-damaged buildings worsens asthma, and remediation improves symptom control and reduces exacerbations. Antifungal therapy is beneficial for fungal asthma as demonstrated in nine of 13 randomised controlled studies, reducing symptoms, corticosteroid need and exacerbations while improving lung function. Other useful therapies include azithromycin and some biologics approved for the treatment of severe asthma. If all individuals with poorly controlled and severe asthma could be 'relieved' of their fungal allergy and infection through antifungal therapy without systemic corticosteroids, the health benefits would be enormous and relatively inexpensive, improving the long term health of over 20 million adults and many children. Antifungal therapy carries some toxicity, drug interactions and triazole resistance risks, and data are incomplete. Here we summarise what is known and what remains uncertain about this complex topic. [ABSTRACT FROM AUTHOR]

Recurrent aphthous stomatitis is one of the most common ulcerative disorders associated with oral mucosa. The etiology of recurrent aphthous stomatitis remains unclear and is considered idiopathic. Several plausible triggers have been studied as predisposing to recurrent aphthous stomatitis, where one of the predisposing factors is allergy. This study aimed to determine the relationship between recurrent aphthous stomatitis and allergy through a history of allergy and IgE levels. The study involved 50 recurrent aphthous stomatitis patients. The inclusion criteria included patients with minor type recurrent aphthous stomatitis, who do not have a systemic disease or take any drug, do not use orthodontic appliances, and are voluntarily willing to be the study subject. Recurrent aphthous stomatitis is diagnosed with anamnesis to determine the recurrence of recurrent aphthous stomatitis and history of allergy and clinical examination to examine the ulcer of recurrent aphthous stomatitis. After that, patients had blood samples taken for IgE levels. The data obtained were then analyzed for the relationship between allergy history and IgE with chi-square. Patients with a history of allergy mainly had a high value of IgE with 12 (85,7%). There was a significant relationship between the history of allergy and IgE levels of recurrent aphthous stomatitis patients with a p-value of 0.013 (p<0.05). It can be concluded that it is crucial to examine the history of allergy and perform laboratory examinations to search for predisposing factors in recurrent aphthous stomatitis patients. [ABSTRACT FROM AUTHOR]