Structure-based epitope prediction and assessment of cross-reactivity of Myrmecia pilosula venom-specific IgE and recombinant Sol g proteins (Solenopsis geminata).

The global distribution of tropical fire ants (Solenopsis geminata) raises concerns about anaphylaxis and serious medical issues in numerous countries. This investigation focused on the cross-reactivity of allergen-specific IgE antibodies between S. geminata and Myrmecia pilosula (Jack Jumper ant) venom proteins due to the potential emergence of cross-reactive allergies in the future. Antibody epitope analysis unveiled one predominant conformational epitope on Sol g 1.1 (PI score of 0.989), followed by Sol g 2.2, Sol g 4.1, and Sol g 3.1. Additionally, Pilosulin 1 showed high allergenic potential (PI score of 0.94), with Pilosulin 5a (PI score of 0.797) leading in B-cell epitopes. The sequence analysis indicated that Sol g 2.2 and Sol g 4.1 pose a high risk of cross-reactivity with Pilosulins 4.1a and 5a. Furthermore, the cross-reactivity of recombinant Sol g proteins with M. pilosula-specific IgE antibodies from 41 patients revealed high cross-reactivity for r-Sol g 3.1 (58.53%) and r-Sol g 4.1 (43.90%), followed by r-Sol g 2.2 (26.82%), and r-Sol g 1.1 (9.75%). Therefore, this study demonstrates cross-reactivity (85.36%) between S. geminata and M. pilosula, highlighting the allergenic risk. Understanding these reactions is vital for the prevention of severe allergic reactions, especially in individuals with pre-existing Jumper Jack ant allergy, informing future management strategies.

Clinical Relevance of Lepidoglyphus destructor Sensitisation in Allergic Rhinitis: Nasal Provocation Test as in vivo Assessment.

BACKGROUND: Dust mites are the leading cause of respiratory allergic diseases worldwide. Allergy to storage mites (SMs) has mostly been related to occupational exposures. However, recent studies have shown that sensitisation to SM, such as Lepidoglyphus destructor (Lep d), is of considerable importance also in urban populations, with high prevalence in dust samples of domestic environments. Co-sensitisation between house dust mites (HDMs) and SM is now regarded as very frequent in some regions, and cross-reactivity between them seems to be narrow. Therefore, SM allergenic capacity is increasingly a subject of study. The nasal provocation test (NPT), as an in vivo technique, could be considered the gold standard for the clinical relevance assessment of an allergen, in polysensitised rhinitis patients. OBJECTIVE: The objective of this study was to analyse the clinical relevance of the SM Lep d, by assessing the relationship between in vivo sensitisation and expression of allergic respiratory disease in an urban setting. PATIENTS AND METHODS: In our study, we enrolled a total of 32 allergic patients with rhinitis (with or without asthma) with proven sensitisation by skin prick test (SPT) and specific IgE (sIgE) to HDMs and/or SM. Patients underwent NPT with Lep d using subjective (Lebel Symptom Score Scale) and objective measurements (peak nasal inspiratory flow [PNIF]) for assessment of nasal response. RESULTS: Most of the patients with positive SPT and sIgE to Lep d had a positive NPT (24/27; 89%). True Lep d allergy, assessed by a positive NPT, could be predicted by a SPT wheal size >9.7 mm and a sIgE >0.42 kUA/L, with 100%/95.7% sensitivity and 75.0%/83.3% specificity, respectively. Co-sensitisation between Lep d and Der p was high, 75.0%. Asthma was more frequent in the positive Lep d NPT group (54 vs. 12%, p < 0.05). Significantly more patients from this group reported physical exercise, nonspecific irritants, and respiratory infections as relevant triggers of respiratory symptoms (p < 0.01-p < 0.05). CONCLUSIONS: To our knowledge, this is the first study to show that sensitisation to Lep d may have clinical relevance in a non-occupational setting. In this group, there seems to be a relationship between allergy to Lep d and severity of respiratory disease, with more bronchial inflammation, when comparing with mite-allergic patients sensitised only to HDM. Therefore, the authors consider that sensitisation to Lep d should be considered when assessing and treating allergic respiratory disease in urban environments.

Clinical and immunological allergy assessment in cancer patients.

Cancer is associated with immunodeficiency, while allergies result from immune system hyperactivity mediated by cytokines and immunoglobulins. The purpose of this study was to determine the relationship between immune environment of specific cancers and allergies, emphasizing cytokines related to Th1 and Th2 responses associated with IgE. 80 adults were distributed into two groups: control (n = 20) and cancer (n = 60), distributed in three subgroups (n = 20), head and neck, stomach, and prostate cancers. This study compared Th1 (IL-2) and Th2 (IL-4) parameters, anti-inflammatory, pro-inflammatory, or regulatory profile regarding both IgE levels and reported allergies, by means of clinical manifestations and IgE, IL-1ß, IL-2, IL-4, IL-17, and TGF-ß serum concentration. Clinically allergies were observed in 50% of the control group and in 20% of the cancer group (p = 0.009). IL-2 cytokine and TGF-ß concentrations were higher in the patients with cancer as compared to the control (p < 0.005). However, there were IL-4, IL-17, and IL-1ß decreases in the patients with cancer (p < 0.05). No correlation was observed between the cytokines studied and IgE and clinically proven allergies in both investigated groups. There was an inverse association between cancer and clinical allergy manifestations. In head and neck, stomach, and prostate cancers, an immunosuppressive serum tumor environment was predominant. There was no difference in cytokines related to Th1 and Th2 parameters in relation to IgE. No correlation was found between clinically proved allergies and immunity markers related to the same allergens.

A systematic assessment of structural heterogeneity and IgG/IgE-binding of ovalbumin.

Ovalbumin (OVA), one of the major allergens in hen egg, exhibits extensive structural heterogeneity due to a range of post-translational modifications (PTMs). However, analyzing the structural heterogeneity of native OVA is challenging, and the relationship between heterogeneity and IgG/IgE-binding of OVA remains unclear. In this work, ion exchange chromatography (IXC) with salt gradient elution and on-line detection by native electrospray ionization mass spectrometry (ESI MS) was used to assess the structural heterogeneity of OVA, while inhibition-ELISA was used to assess the IgG/IgE binding characteristics of OVA. Over 130 different OVA proteoforms (including glycan-free species and 32 pairs of isobaric species) were identified. Proteoforms with acetylation, phosphorylation, oxidation and succinimide modifications had reduced IgG/IgE binding capacities, whereas those with few structural modifications had higher IgG/IgE binding capacities. OVA isoforms with a sialic acid-containing glycan modification had the highest IgG/IgE binding capacity. Our results demonstrate that on-line native IXC/MS with salt gradient elution can be used for rapid assessment of the structural heterogeneity of proteins. An improved understanding of the relationship between IgG/IgE binding capacity and OVA structure provides a basis for developing biotechnology or food processing methods for reducing protein allergenicity reduction.

Recent Advances in Allergen-Specific Immunotherapy as Treatment for Allergic Asthma: A Practical Overview.

The Global Initiative for Asthma Report updated in 2019 stated that potential benefits of allergen immunotherapy (AIT), compared to pharmacological and avoidance options, must be weighed against the risk of adverse effects and the inconvenience and cost of the prolonged course of therapy in asthma. Thus, with the aim of clarifying some aspects with regard to the possible use of AIT in allergic asthma treatment armamentarium, a group of expert allergists from the Spanish Allergy and Clinical Immunology Scientific Society (SEAIC), particularly from the Immunotherapy and Asthma Interest Groups developed a frequently asked questions in clinical practice. This document updates relevant topics on the use of AIT in asthma and could facilitate physician clinical decisions and improve health outcomes for individual patients.

The use of microarray and other multiplex technologies in the diagnosis of allergy.

OBJECTIVE: To give an overview and describe the strengths and weaknesses of immunoglobulin E (IgE) microarray and other multiplex assays that have been developed and are being used for allergy diagnostics. DATA SOURCES: Queries for IgE microarray and multiplex assays were conducted with PubMed and Google Scholar, searching for primary articles and review papers. STUDY SELECTIONS: We focused on articles written in English on commercially available IgE multiplex assays that were reported in the allergy and immunology literature. RESULTS: Several commercial IgE assays that use microarray or other multiplex technology have been developed, and some have been implemented into clinical practice in Europe and Asia, with the Immuno Solid-Phase Allergen Chip being the most widely studied. Results of these assays generally correlate with results using "singleplex" IgE assays (eg, ImmunoCAP), though there can be variability among products and among allergens. A strength of the microarray technology is that IgE to a large number of allergens can be detected simultaneously in a single test, and only a small amount of patient serum is required. Cost, inadequate sensitivity under some scenarios, and difficulties with data interpretation, in some cases of 100 or more allergens, can be limitations. CONCLUSION: IgE microarray assays are already a valuable tool in research applications. These assays, and also other forms of IgE multiplex assays, are likely to play an important role in the clinical practice of allergy in the future. Additional studies focused on clinical outcomes, and the development of more targeted allergen panels could facilitate increased clinical use.

Pistachio and cashew nut allergy in childhood: Predictive factors towards development of a decision tree.

BACKGROUND: Pistachio and cashew nut, which belong to the same botanical family, are tree nuts that induce serious allergic reactions. OBJECTIVE: We aimed to determine the predictive factors for pistachio and cashew nut reactivity during oral food challenge (OFC). METHODS: A total of 112 pistachio and/or cashew nut sensitized children, aged 58.45 (IQR:40.38-88.32) months, were included. Cutoff values and probability curves for skin prick test (SPT), sIgE, sIgE/Total IgE that predict reactivity were determined for pistachio and cashew nut. Additionally, a diagram was created that can be useful while making a decision for OFC based on SPT and sIgE values. RESULTS: A total of 73 patients underwent OFC with pistachio and/or cashew nut. Twelve children with current anaphylaxis history were not challenged and accepted as allergic. SPT was the only predictive factor for positive pistachio/ cashew nut OFC. According to area under curve (AUC) analysis, SPT was more predictive than sIgE and sIgE/Total IgE both for pistachio and cashew nut. Optimal cutoff values according to "Youden index" for pistachio SPT, sIgE, and sIgE/ Total IgE were 7.25 mm, 4.14 kUA/L, and 1.32%, respectively. And those values for cashew nut SPT, sIgE, and sIgE/Total IgE were 6.25 mm, 1.125 kUA/L, and 3.30%, respectively. The diagram showed that SPT predicted the reactivity together with sIgE better than only the SPT values. CONCLUSION: SPT was the best predictor for reactivity both for pistachio and cashew nut. Combined use of SPT and sIgE may improve the prediction of reactivity at pistachio and cashew nut OFCs in children.

Assessment of Immune Responses in an Animal Model of Wheat Food Allergy via Epicutaneous Sensitization.

Wheat allergy is a pathological event involving immunocompetent cells against ingested wheat allergen and is clearly associated with transdermal sensitization. However, the molecular mechanisms involved in the disease etiology are not completely understood. A complex cellular and tissue network linking to food allergy makes it difficult to understand the molecular mechanism of allergenicity. Animal models are valuable tools to deduce basic principles of human disease without invasive intervention trials. A mouse model of wheat allergy has provided insights into effects of skin exposure to wheat protein; it is a plausible route of human sensitization for wheat anaphylaxis. Further investigation of this model will capture the essential occurrence and flow of events, bringing useful clues to develop effective treatment and control strategies against wheat allergy. Here, we describe a method for analyzing the expression of cell surface molecules in single cells isolated from lymphoid tissue with flow cytometry. Sensitization by wheat extracts significantly increases antigen-specific T cells in the spleen. Collecting information regarding the contribution of immune cells to allergic sensitization in the development of wheat allergy would be useful in preventing and treating food allergies.

Allergic rhinitis.

Allergic rhinitis (AR) is caused by immunoglobulin E (IgE)-mediated reactions to inhaled allergens and is one of the most common chronic conditions globally. AR often co-occurs with asthma and conjunctivitis and is a global health problem causing major burden and disability worldwide. Risk factors include inhalant and occupational allergens, as well as genetic factors. AR impairs quality of life, affects social life, school and work, and is associated with substantial economic costs. The Allergic Rhinitis and its Impact on Asthma (ARIA) initiative classified AR into intermittent or persistent and mild or moderate/severe. The diagnosis is based on the clinical history and, if needed in patients with uncontrolled rhinitis despite medications or with long-lasting symptoms, on skin tests or the presence of serum-specific IgE antibodies to allergens. The most frequently used pharmacological treatments include oral, intranasal or ocular H1-antihistamines, intranasal corticosteroids or a fixed combination of intranasal H1-antihistamines and corticosteroids. Allergen immunotherapy prescribed by a specialist using high-quality extracts in stratified patients is effective in patients with persistent symptoms. Real-world data obtained by mobile technology offer new insights into AR phenotypes and management. The outlook for AR includes a better understanding of novel multimorbid phenotypes, health technology assessment and patient-centred shared decision-making.

Biologics for the Treatment of Food Allergies.

Food allergy is increasingly prevalent and poses a life-threatening risk to those afflicted. The health care costs associated with food allergies are also increasing. Current and emerging treatments for food allergies aim at protecting against reactions caused by accidental ingestion and increasing the food allergen reaction threshold, although this protection is often temporary. In the future, ideal biologic therapies would target key mediators of the type II immune pathway, essential in development of the atopic march to prevent development of food allergies. Biologics offering long-term protection against allergic reactions to food are needed, and several agents are already in development.

Immunoglobulin E (IgE)-Mediated Food Allergy in Children: Epidemiology, Pathogenesis, Diagnosis, Prevention, and Management.

A food allergy is an immunoglobulin E (IgE)-mediated hypersensitive reaction to food, which consists in the appearance of allergic symptoms; it can vary from common urticaria to even fatal anaphylaxis. The prevalence of food allergies has been increasing in the past twenty years and it represents a major public health problem in industrialized countries. The mechanism that leads to food allergies is the lack of immunologic and clinical tolerance to food allergens. The diagnosis of IgE-mediated food allergies is based on the combined use of a detailed medical history, in-vivo, and in-vitro research of specific IgE, the elimination diet, and the double-blind placebo-controlled food challenge. The only currently available treatment for allergies is the strict elimination diet. This type of attitude, which we could define as "passive", does not overcome the risk of accidental reactions due to involuntary intake of the culprit food. For food allergy management, an "active" approach is urgently needed, such as specific allergen immunotherapy, which is currently under development and only used for research purposes. This article aims to give an updated review of IgE-mediated food allergies in pediatric populations in terms of epidemiology, pathogenesis, prevention, diagnosis, and management.

Structural analysis and allergenicity assessment of an enzymatically cross-linked bovine α-lactalbumin polymer.

Enzymatic cross-linking is frequently used in bio-processing of dairy products since it could change the physiochemical and functional characterization. In our study, bovine α-lactalbumin was cross-linked by polyphenol oxidase from Agaricus bisporus and the changes in the structure, digestibility and allergenicity of α-lactalbumin were explored after cross-linking, and the structural alterations of the polymers were analyzed by circular dichroism spectroscopy, ultraviolet absorption spectroscopy and fluorescence spectroscopy. The digestibility of cross-linked α-lactalbumin was evaluated by simulated digestion in vitro. After that, the allergenicity of α-lactalbumin polymers was evaluated by detection of the specific IgE binding ability using an animal model. The results showed that the secondary and tertiary structures of various α-lactalbumin polymers exhibited a significant variation compared with those of untreated α-lactalbumin, and the cross-linked α-lactalbumin was relatively less susceptible to digestion. Moreover, the allergenicity of cross-linked polymers decreased significantly. These results suggested that there was a direct correlation between a loss of an α-helix and IgE binding to α-lactalbumin, which indicated that enzymatic cross-linking might be an efficient approach to reduce the allergenicity of bovine α-lactalbumin.

The use of biologic therapies for the management of pediatric asthma.

With better understanding of the role of type 2 inflammation in allergic asthma, there has been progress made in the development of new biologic therapies targeting these specific pathways. This review will consider diagnostic criteria for using biologic therapies for pediatric asthma with special emphasis on populations that are likely to benefit the most from particular therapies. With the exception of the anti-immunoglobulin E, omalizumab, very few studies have been published on the efficacy and safety of biologic therapies in children, particularly anti-interleukin-5 (IL5) and anti-IL4/IL13 therapies. The review will highlight the scarcity of published data in pediatric-specific populations. In addition, we will consider the cost-effectiveness as well as potential long-term consequences of biologic therapies in pediatric asthma.

Economic evaluation and budgetary burden of mepolizumab in severe refractory eosinophilic asthma.

OBJECTIVE: Mepolizumab is indicated as an additional treatment of severe refractory eosinophilic asthma. The observed differences in  population subgroups according to plasma eosinophil count, the  existence of patients with high levels of immunoglobulin E who are  candidates of omalizumab and mepolizumab, as well as mepolizumab's  economic impact, lead to make efficient economic studies for clinical  decision making. The aim was to analyze mepolizumab's cost-efficacy  and budget impact. METHOD: Cost comparison and the use of mepolizumab's budgetary  impact was performed, from the Spanish National Health System's  perspective. Among the assessed alternatives, inhaled systemic  corticosteroids, plus long acting beta agonist (ß2) and/or oral systemic  corticosteroids in patients with non immunoglobulin E-mediated severe  allergic asthma, and said treatment along with omalizumab in patients  with immunoglobulin E mediated eosinophilic allergic asthma were  included. Its efficacy was evaluated through avoided clinically relevant  exacerbations. The direct costs associated with exacerbation were  assessed. RESULTS: Mepolizumab's long run average incremental cost regarding omalizumab's is 797 euros per patient a year. Considering  omalizumab's alternative discounted price, including mepolizumab for  patients with immunoglobulin E mediated eosinophilic allergic asthma  would increase public spending from 2.3 to 4.6 million euros. Given  omalizumab's notified price, the gradual introduction of mepolizumab in  the Spanish National Health System would save 3.6 million euros in  three years. For non immunoglobulin E-mediated severe asthma  patients, the avoided cost/exacerbation by introducing mepolizumab is  15,085 euros, assuming a gradual market penetration of mepolizumab. In patients with ≥ 500 eosinophils/µL, this cost decreases to 7,767  euros per avoided exacerbation with a budgetary impact of 183.2 million  euros in three years with a progressive penetration of mepolizumab. CONCLUSIONS: The cost comparison between mepolizumab and  omalizumab in immunoglobulin E mediated eosinophilic asthma patients  suggests a use of the lower cost drug, promoting price competition.  Additionally, prioritizing its use among non immunoglobulin E-mediated  severe refractory eosinophilic asthma patients and ≥ 500 eosinophils/µL  plasma level patients, would improve its efficiency as well as  reducing its budgetary impact.

Objetivo: Mepolizumab está indicado como tratamiento adicional del asma eosinofílica refractaria grave. Las diferencias observadas en  subgrupos poblacionales según recuento eosinofílico plasmático,  existencia de pacientes con altos niveles de inmunoglobulina E  candidatos a omalizumab y mepolizumab, e impacto económico de  mepolizumab obligan a realizar estudios económicos para tomar  decisiones clínicas eficientes. El objetivo fue realizar un análisis de  coste/eficacia e impacto presupuestario de mepolizumab.Método: Se realizó la comparación de costes e impacto presupuestario del uso de mepolizumab desde la perspectiva del  Sistema Nacional de Salud. Las alternativas valoradas fueron  corticosteroides sistémicos inhalados + agonista ß2 de larga duración  y/o corticosteroides sistémicos orales en pacientes con asma alérgica  grave no mediada por inmunoglobulina E, y este tratamiento junto a  omalizumab en pacientes con asma eosinofílica alérgica mediada por  inmunoglobulina E. La eficacia se evaluó mediante exacerbaciones  clínicamente relevantes evitadas. Se valoraron los costes directos  asociados a exacerbación.Resultados: El coste incremental medio de mepolizumab respecto a omalizumab es de 797 euros por paciente y año. Considerando precio alternativo con descuento de omalizumab, incluir mepolizumab  para pacientes con asma eosinofílica alérgica y mediada por  inmunoglobulina E supondría incrementar el gasto público de 2,3 a 4,6  millones de euros. Teniendo en cuenta el precio notificado de  omalizumab, la introducción gradual de mepolizumab en el Sistema  Nacional de Salud supondría ahorrar 3,6 millones de euros en tres años.  Para pacientes con asma grave no mediada por inmunoglobulina  E, el coste/exacerbación evitada al añadir mepolizumab es de 15.085  euros, con un impacto presupuestario en tres años de 578,4 millones de  euros, asumiendo una penetración progresiva de mepolizumab en el  mercado. En los pacientes con ≥ 500 eosinófilos/µl, este coste  disminuye a 7.767 euros por exacerbación evitada, con un impacto  presupuestario de 183,2 millones de euros en tres años con penetración  progresiva de mepolizumab.Conclusiones: La comparación de costes entre mepolizumab y  omalizumab en pacientes con asma eosinofílica mediada por  inmunoglobulina E señala como razonable utilizar el fármaco de menor  coste, promoviendo competencia de precios. Asimismo, priorizar su uso  en pacientes con asma eosinofílica refractaria grave no mediada por  inmunoglobulina E y niveles plasmáticos ≥ 500 eosinófilos/µl permitiría  mejorar la eficiencia y disminuir el impacto presupuestario.

Optimization of induction parameters, structure quality assessment by ATR-FTIR and in silico characterization of expressed recombinant polcalcin in three different strains of Escherichia coli.

The inhalation of Chenopodium album (C. album) pollen, especially polcalcin (Che a 3), has been reported as a significant source of allergic respiratory symptoms. This study was conducted to characterize biophysical differences of recombinant polcalcin come from three different Escherichia coli strains using attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), optimize recombinant polcalcin expression, and linear B-cell epitopes identification using in silico methods. ATR-FTIR results of purified proteins showed spectra intensity variance in the amide I region, while there were no changes in pick position and shape of the bands. SHuffle® T7 Express was selected for subsequent optimization due to ability in the correction of the mis-oxidized bonds and promotes proper folding which was validated by ATR-FTIR analysis results. Then, Response Surface Methodology was performed to optimize critical factors including induction temperature, duration of induction, and concentration of inducer. The best partitioning conditions were achieved in 1.5 mM IPTG for 10.97 h at 29.9 °C. Finally, prediction of polcalcin B-cell epitopes was carried out which indicated the presence of 4 different epitopes. Together, the results may help to the development of diagnostic approaches and also vaccine manufacture for desensitization and modulation of the allergic response in patients.

Allergic reactions to penicillins and cephalosporins: diagnosis, assessment of cross-reactivity and management.

Introduction: Beta-lactams (BL) are the main cause of allergic drug reactions mediated by specific immunological mechanisms. Reactions can be IgE or effector T-cell mediated. The new antigenic determinants are recognized by the immunological system in the context of the common beta-lactam structure or the specific differences in the side chains of the antibiotics of this family plus the protein carrier. Areas covered: We have reviewed the recent clinical literature concerning new clinical entities, the progress in diagnosis including the difficulties for in in vivo and or in vitro testing as well as the new algorithms proposed for delabelling subjects classified as allergic to beta-lactams, and recommendations for desensitization procedures. Expert opinion: The knowledge gained over the last years on beta-lactam hypersensitivity has enabled a better understanding and management of cases with allergic reactions to beta-lactams.

Cost-effectiveness of using an extensively hydrolyzed casein formula supplemented with Lactobacillus rhamnosus GG in managing IgE-mediated cow's milk protein allergy in the UK.

Objective: To estimate the cost-effectiveness of using an extensively hydrolyzed casein formula (eHCF) plus the probiotic Lactobacillus rhamnosus GG (eHCF plus LGG; Nutramigen* LGG®) compared to an eHCF alone as first-line dietary management for Immunoglobulin E (IgE)-mediated cow's milk protein allergy (CMPA) in the UK. Methods: Decision modelling was undertaken to estimate the probability of IgE-mediated cow's milk allergic infants being symptom free (i.e. not experiencing urticaria, eczema, asthma or rhinoconjunctivitis) and developing tolerance to cow's milk by 5 years. The model also estimated the cost (at 2016/2017 prices) of healthcare resource use funded by the UK's National Health Service (NHS) over 5 years after starting a formula, as well as the relative cost-effectiveness of the two dietary formulae. Results: At 5 years after the start of a formula the probability of being symptom free was estimated to be 0.97 and 0.76 among infants who were originally fed eHCF plus LGG and an eHCF alone, respectively. This encompassed the probability of children being asthma free at 5 years after the start of treatment, which was 0.99 and 0.91 in the eHCF plus LGG and eHCF alone groups, respectively. Additionally, the probability of acquiring tolerance to cow's milk was estimated to be 0.94 and 0.66 among infants who were originally fed eHCF plus LGG and an eHCF alone, respectively. The estimated total healthcare cost over 5 years of initially feeding infants with eHCF plus LGG was less than that of feeding infants with an eHCF alone (£4229 versus £5136 per patient). Conclusions: First-line management of newly diagnosed infants with IgE-mediated CMPA with eHCF plus LGG instead of an eHCF alone improves outcome, releases healthcare resources for alternative use, reduces the NHS cost of patient management and thereby affords a cost-effective dietetic strategy to the NHS.

Assessment of serum allergen-specific IgE levels in horses with seasonal allergic dermatitis and recurrent airway obstruction in Spain.

Allergic conditions are prevalent equine diseases that can be diagnosed by clinical examination alone, but definitive diagnosis is more likely with laboratory testing. The ELISA Allercept© test was used to analyse the serum samples of 73 horses with allergic diseases. Sixty-one horses (83.5%) had allergen-specific IgE levels ≥ 150 ELISA Units (EU), the cut-off defined by the assay. Fifty-four horses had allergic dermatitis (AD) with high IgE levels to Tyrophagus putrescentiae (51.9%), Rumex crispus (48.1%), Tabanus (46.3%) and Dermatophagoides farinae/ D. pteronyssinus (40.7%). Seven horses with recurrent airway obstruction (RAO) had a high prevalence of T. putrescentiae (85.7%), followed by that of Acarus siro (57.1%) and D. farinae/D. pteronyssinus (57.1%). Horses affected with RAO had more positive reactions to mites (2.22 ± 0.84) than did horses with AD (1.51 ± 0.61, P < 0.05). A strong correlation of serum allergen-specific IgE level was found between Culex tarsalis and Stomoxys (r = 0.943) and between Dactylis glomerata and both Secale cereale (r = 0.79) and R. crispus (r = 0.696). These results indicate that among horses with allergic diseases in Spain, ELISA tests demonstrated a high prevalence of serum allergen-specific IgE in response to mites. Our study emphasises the importance of laboratory testing and updating allergy panels to improve the likelihood of a definitive diagnosis and the identification of allergens that should be included in allergic disease treatment.

Uncharted Waters: Challenges in the Era of Biologic Therapies for Nasal Polyposis.

Several new, promising, targeted therapies for nasal polyposis are being tested in large-scale clinical trials. These agents target pathways thought to be involved in the disease, including IgE, IL-5, IL-4/IL-13, and others. Designing these trials poses significant challenges: who and when to enroll is not completely clear, optimal dosing is not known, outcome measures are insufficiently robust, there are no validated biomarkers, trial regimens may not comport with how clinicians might use these drugs once approved, and cost-benefit ratios have not been assessed. Thus, there is a need to consider such questions, as trials of these novel treatments continue and these biologics become available. Despite these uncertainties about trial design, there remains a great deal of excitement in the field as we approach the dawn of a new era of therapeutic options for nasal polyposis. In this rostrum, we enumerate these issues and call for a conference that will allow stakeholders in the field to confront them as we enter this new era of opportunity to advance the treatment of nasal polyposis.