Allergy Research Research Articles

The clinical burden of food allergies: Insights from the Food Allergy Research & Education (FARE) Patient Registry

BackgroundFood allergies are serious and potentially life-threatening, and often place a large burden on patients and their caregivers, including impacts on quality of life. ObjectiveTo assess the real-world patient burden of food allergies, using self-reported data available from the Food Allergy Research & Education (FARE) Patient Registry (NCT04653324). MethodsThe FARE Patient Registry is voluntary and captures real-world experiences of adults and pediatric patients in the United States, and their caregivers, through a series of surveys assessing patient health and experiences with food allergies. Self-reported data were descriptively analyzed. ResultsThe FARE study cohort included 5587 patients with food allergies; 82% had multiple food allergies and 62% were aged <18 years. About half of the patients were first diagnosed by an allergist/immunologist (53%), most commonly with a skin prick test (71%) or a serum immunoglobulin E test (62%). This analysis found that food allergies (most commonly peanut [66%], tree nuts [61%], egg [43%], and milk [37%]) impart a large clinical burden on patients, many of whom experience food-related allergic reactions and comorbidities. Many patients experienced >1 food-related allergic reaction per year (42%), with 46% experiencing food-induced anaphylaxis. Half of all food-related allergic reactions occurred at home. Accidental exposures to food allergens were experienced by 77% of patients. The most common allergic comorbidities reported by patients with food allergies were atopic dermatitis (48%), asthma (46%), and allergic rhinitis (39%). The clinical burden of food allergies were found to be greater in patients with multiple food allergies, and different for adults versus pediatric patients. ConclusionThis is the first study to assess patient experience and disease burden information from patients contributing to the FARE Patient Registry, thus providing a unique insight into the lives of patients in the United States with food allergies. These insights may assist clinicians and other public health stakeholders in the management of patients with food allergies.

[Translated article] Four-year Epidemiological Surveillance of the Spanish Registry of Research in Contact Dermatitis and Cutaneous Allergy: Current Situation and Trends

BackgroundThe epidemiological surveillance of contact dermatitis is one of the objectives of the Spanish Registry of Research in Contact Dermatitis and Cutaneous Allergy. Knowing whether the prevalence of positive tests to the different allergens changes over time is important for this monitoring process. ObjectivesTo describe the various temporary trends in allergen positivity in the GEIDAC standard series from 2018 through December 31, 2022. MethodsThis was a multicenter, observational trial of consecutive patients analyzed via patch tests as part of the study of possible allergic contact dermatitises collected prospectively within the Spanish Registry of Research in Contact Dermatitis and Cutaneous Allergy. The data was analyzed using 2 statistical tests: one homogeneity test (to describe the changes seen over time) and one trend test (to see whether the changes described followed a linear trend). ResultsA total of 11327 patients were included in the study. Overall, the allergens associated with a highest sensitization were nickel sulfate, methylisothiazolinone, cobalt chloride, methylchloroisothiazolinone/methylisothiazolinone, and fragrance mix i. A statistically significant decrease was found in the percentage of methylisothiazolinone positive tests across the study years with an orderly trend. ConclusionsAlthough various changes were seen in the sensitizations trends to several allergens of the standard testing, it became obvious that a high sensitization to nickel, methylchloroisothiazolinone/methylisothiazolinone and fragrances mix i remained. Only a significant downward trend was seen for methylisothiazolinone.

Analytical challenges in omics research on asthma and allergy: A National Institute of Allergy and Infectious Diseases workshop

Studies of asthma and allergy are generating increasing volumes of omics data for analysis and interpretation. The National Institute of Allergy and Infectious Diseases (NIAID) assembled a workshop comprised of investigators studying asthma and allergic diseases using omics approaches, omics investigators from outside the field, and NIAID medical and scientific officers to discuss the following areas in asthma and allergy research: genomics, epigenomics, transcriptomics, microbiomics, metabolomics, proteomics, lipidomics, integrative omics, systems biology, and causal inference. Current states-of-the art, present challenges, novel and emerging strategies, and priorities for progress were presented and discussed for each area. This workshop report summarizes the major points and conclusions from this NIAID workshop. As a group, the investigators underscored the imperatives for rigorous analytic frameworks, integration of different omics data types, cross-disciplinary interaction, strategies for overcoming current limitations, and the overarching goal to improve scientific understanding and care of asthma and allergic diseases.

STATE-OF-THE-ART OF GLOBAL START-UP INVESTMENT FOR ALLERGY AND IMMUNOLOGY 2022

In 2022, the "New Capitalism Grand Design and Implementation Plan" was adopted in Japan, emphasizing the promotion and environmental development of startups. Given this context, an investigation into the startup and investment landscape in the allergy sector, both domestically and internationally, becomes imperative. We analyzed 156 allergy-related startups from Japan, the US, and Europe from 2010 to 2021. Data on corporate information and investment trends were extracted from databases and VC websites. The total investment reached approximately 7.2 billion USD, with a ratio of 20:6:1 for the US, Europe, and Japan, respectively. The US showed a decline post its peak from 2016-2018, while Europe and Japan experienced growth. Notably, the US primarily invested in biopharmaceuticals for atopic dermatitis and food allergies, Europe in asthma-related apps, and Japan in healthcare apps and cross-border startups. While Japan's investment environment in the allergy sector remains in its nascent stages and has room for development, the US and Europe are evidently ahead. Considering the rise of startups and funding limitations in Japan, external funding from regions like the US becomes a potential avenue. These findings are anticipated to contribute to the strategic activation of startups in allergy research and development.

EPOS2020/EUFOREA expert opinion on defining disease states and therapeutic goals in CRSwNP.

Severe chronic rhinosinusitis with nasal polyps (CRSwNP), a form of diffuse bilateral (usually type 2) CRS, is a debilitating disease with a significant impact on quality of life (QoL). With novel knowledge and treatment options becoming available, there is a growing need to update or revise key definitions to enable communication across different specialties dealing with CRS, and to agree on novel goals of care in CRSwNP. The European Forum for Research and Education in Allergy and Airway diseases (EUFOREA) and EPOS expert members discussed how to measure treatment responses and set new treatment goals for CRSwNP. In this paper a consensus on a list of definitions related to CRSwNP is provided: control, remission, cure, recurrence/exacerbation, treatable traits, remodeling, progression, and disease modification. By providing these definitions, the involved experts hope to improve communication between all stakeholders involved in CRSwNP treatment for use in routine care, basic and clinical research and international guidelines aimed to harmonize and optimize standard of care of patients with CRSwNP in the future.

Reaching Communities Through Food Allergy Advocacy, Research, and Education: A Comprehensive Analysis

This article explores the multifaceted approach of food allergy (FA) advocacy, research, and education to address the diverse challenges associated with FA, such as disparities in socioeconomic status, food security, quality of life, and the overall burden of the disease. Advocacy initiatives are instrumental in driving policy changes, raising public awareness, and directing substantial research funding, with a focus on reducing disparities. They have influenced allergen labeling regulations and improved access to epinephrine, emphasizing the importance of school-based management plans, especially in underserved communities. Research in FA informs medical practices and offers them hope for improved treatments. Recent breakthroughs in peanut allergy prevention and oral immunotherapy trials exemplify the potential for advancements while highlighting the need to address disparities in health care access. Education is a critical tool for prevention, raising awareness, and reducing the risk of allergic reactions. Efforts should be tailored to reach marginalized communities, particularly in schools where education on FA management is essential. Collaborating directly with communities is imperative to ensure inclusivity and address disparities. Barriers such as mistrust, language and cultural differences, and lack of diversity among researchers must be overcome to encourage diverse participation in research studies. This article concludes by emphasizing the significance of a comprehensive approach to FA research that prioritizes equity and inclusivity. The call to action highlights the need for global initiatives to reshape the landscape of FA care and address disparities in health care access and outcomes.

PLM4Alg: Protein Language Model-Based Predictors for Allergenic Proteins and Peptides.

The rising prevalence of allergy demands efficient and accurate bioinformatic tools to expedite allergen identification and risk assessment while also reducing wet experiment expenses and time. Recently, pretrained protein language models (pLMs) have successfully predicted protein structure and function. However, to our best knowledge, they have not been used for predicting allergenic proteins/peptides. Therefore, this study aims to develop robust models for allergenic protein/peptide prediction using five pLMs of varying sizes and systematically assess their performance through fine-tuning with a convolutional neural network. The developed pLM4Alg models have achieved state-of-the-art performance with accuracy, Matthews correlation coefficient, and area under the curve scoring 93.4-95.1%, 0.869-0.902, and 0.981-0.990, respectively. Moreover, pLM4Alg is the first model capable of handling prediction tasks involving residue-missed sequences and sequences containing nonstandard amino acid residues. To facilitate easy access, a user-friendly web server (https://f6wxpfd3sh.us-east-1.awsapprunner.com) has been established. pLM4Alg is expected to become the leading machine learning-based prediction model for allergenic peptides and proteins. Its collaboration with other predictors holds great promise for accelerating allergy research.

EUFOREA/EPOS2020 statement on the clinical considerations for chronic rhinosinusitis with nasal polyps care.

Following the European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA) treatment algorithm for chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP), patients suffering from severe uncontrolled CRSwNP are recommended to receive oral corticosteroids, (revision) sinus surgery, systemic biologicals and/or aspirin treatment after desensitization (ATAD). Given the major differences in indications, outcomes, practical considerations, risks and costs of these key pillars of treatment, there is a growing need to define criteria for each treatment option and list the clinically relevant and major considerations for them. This EUFOREA document therefore provides an expert panel overview of the expected outcomes, specific considerations and (contra)indications of the five major treatment arms of severe uncontrolled CRSwNP: oral corticosteroids, primary and revision sinus surgery, biological treatment and ATAD. This overview of treatment considerations is needed to allow physicians and patients to consider the different options in the context of providing optimal and personalized care for severe uncontrolled CRSwNP. In conclusion, the five major treatment options for severe uncontrolled CRSwNP have intrinsic advantages, specific indications and considerations that are of importance to the patient, the physician and the society. This EUFOREA statement supports the unmet need to define criteria for the indication of every treatment pillar of CRSwNP.

Vigilancia epidemiológica en los últimos 4 años del Registro Español de Investigación en Dermatitis de Contacto y Alergia Cutánea: situación actual y tendencias

BackgroundThe epidemiological surveillance of contact dermatitis is one of the objectives of the Spanish Registry of Research in Contact Dermatitis and Cutaneous Allergy. Knowing whether the prevalence of positive tests to the different allergens changes over time is important for this monitoring process. ObjectivesTo describe the various temporary trends in allergen positivity in the GEIDAC standard series from 2018 through December 31, 2022. MethodsThis was a multicenter, observational trial of consecutive patients analyzed via patch tests as part of the study of possible allergic contact dermatitises collected prospectively within the Spanish Registry of Research in Contact Dermatitis and Cutaneous Allergy. The data was analyzed using 2 statistical tests: one homogeneity test (to describe the changes seen over time) and one trend test (to see whether the changes described followed a linear trend). ResultsA total of 11327 patients were included in the study. Overall, the allergens associated with a highest sensitization were nickel sulfate, methylisothiazolinone, cobalt chloride, methylchloroisothiazolinone/methylisothiazolinone, and fragrance mix i. A statistically significant decrease was found in the percentage of methylisothiazolinone positive tests across the study years with an orderly trend. ConclusionsAlthough various changes were seen in the sensitizations trends to several allergens of the standard testing, it became obvious that a high sensitization to nickel, methylchloroisothiazolinone/methylisothiazolinone and fragrances mix i remained. Only a significant downward trend was seen for methylisothiazolinone.

Exploring novel approaches to food allergy management.

Nurse practitioners are likely to encounter pediatric and adult patients with symptoms of food allergy who need an accurate diagnosis, emergency treatment plans, and options for management. The pathophysiology of immunoglobulin E (IgE)-mediated food allergy, current and emerging diagnostics, treatment, and emergency management is briefly reviewed, and promising new and potential future treatment options are discussed. Currently, Food and Drug Administration-approved oral immunotherapy (OIT) treatment for peanut allergy, but clinical trials are underway to explore multiple-allergen OIT and alternate routes for IT such as sublingual and epicutaneous. Treatments that modulate the immune system are also potential treatments for food allergies (FAs), including biologic agents. Omalizumab, an anti-IgE therapy, dupilumab, an interleukin-4Ra receptor monoclonal antibody, and etokimab, an anti-IL-33, are all being studied for the treatment of food allergy. There is hope that these novel therapies for FAs will be a viable option translated to the practice setting in the near future, so that strict avoidance is not the only treatment plan for FAs. Nurse practitioners can support their patients with FAs and their families by keeping abreast of progress in food allergy research and assisting patients to consider novel treatment options, when appropriate, using shared decision making.

Purine Nucleoside Phosphorylase Deficiency in Two Unrelated Patients with Autoimmune Hemolytic Anemia and Eosinophilia: Two Novel Mutations.

Two Iranian patients with purine nucleoside phosphorylase (PNP) deficiency are described in terms of their clinical and molecular evaluations. PNP deficiency is a rare form of combined immunodeficiency with a profound cellular defect. Patients with PNP deficiency suffer from variable recurrent infections, hypouricemia, and neurological manifestations. Furthermore, patient 1 developed mild cortical atrophy, and patient 2 presented developmental delay, general muscular hypotonia, and food allergy. The two unrelated patients with developed autoimmune hemolytic anemia and T cells lymphopenia and eosinophilia were referred to Immunology, Asthma and Allergy Research Institute (IAARI) in 2019. After taking blood and DNA extraction, genetic analysis of patient 1 was performed by PCR and direct sequencing and whole exome sequencing was applied for patient 2 and the result was confirmed by direct sequencing in the patient and his parents. The genetic result showed two novel variants in exon 3 (c.246_285+9del) and exon 5 (c.569G>T) PNP (NM_000270.4) in the patients, respectively. These variants are considered likely pathogenic based on the American College of Medical Genetics and Genomics (ACMG) guideline. PNP deficiency has a poor prognosis; therefore, early diagnosis would be vital to receive hematopoietic stem cell transplantation (HSCT) as a prominent and successful treatment.

Development and evaluation of mouse anti-Ara h 1 and Ara h 3 IgE monoclonal antibodies for advancing peanut allergy research

Immediate hypersensitivity reactions to peanuts are a considerable public health concern due to the acute and severe IgE mediated reactions. To conduct research on the pathogenesis and therapeutics of peanut allergies, it is imperative to have mouse anti-crude peanut extract (CPE) IgE monoclonal antibodies (mAbs) for both in-vitro and in-vivo assays. Without these tools, it is difficult to advance research in this field.In this study, four hybridomas producing anti-CPE IgE mAbs were developed and the IgE mAbs were validated using immune-blot analysis, Sandwich ELISA, Indirect ELISA, a cell-based assay using RBL-2H3 cells, and footpad type I hypersensitivity reaction studies in mice.The results indicate that two of the four mAbs can be effectively used for both in-vitro and in-vivo peanut allergy studies, as they induce allergic reactions with sensitization alone in mice. These novel anti-Ara h1 and Ara h 3 IgE mAbs, in combination with the detailed protocols outlined in this article, offer valuable guidance for studying acute allergic reactions involving mast cells across various platforms. With some considerations, the IgE mAbs can significantly advance peanut allergy research.

Promises and Remaining Challenges for Further Integration of Basophil Activation Test in Allergy-Related Research and Clinical Practice.

More than 20 years after having been initially proposed, the relevance and usefulness of basophil activation test (BAT) for the field of allergy research and testing were demonstrated on many occasions. Leveraging the fully open format of a flexible, whole blood-based functional assay, BAT has been shown to be equally important for fundamental research, clinical research, and diagnosis. Regardless of whether the focus of a study is on the characterization of the allergenic moiety, on the patient side, or on the study of the fundamental processes involved in the allergic disease or its treatment, BAT enables the gathering of very important insights. In spite of this, its full capabilities have yet to be leveraged. Various bottlenecks, including but not limited to assay logistics, robustness, flow cytometry access, and/or expertise, have indeed been limiting its development beyond experts and long-term users. Now, various initiatives, aiming at resolving these bottlenecks, have been launched. If successful, a broader use of BAT could then be contemplated. In such a situation, its more thorough integration in clinical practice has the potential to significantly change the allergic patient's journey.

Food allergy symptoms in adults and children using the Food Allergy Research & Education Patient Registry

Food allergy symptoms in adults and children using the Food Allergy Research & Education Patient Registry

Safety and durable immunogenicity of the TV005 tetravalent dengue vaccine, across serotypes and age groups, in dengue-endemic Bangladesh: a randomised, controlled trial

Morbidity and mortality from dengue virus (DENV) is rapidly growing in the large populations of south Asia. Few formal evaluations of candidate dengue vaccine candidates have been undertaken in India, Pakistan, or Bangladesh. Tetravalent vaccines must be tested for safety and immunogenicity in all age groups and in those previously exposed and naive to DENV infections. TV005 is a live, attenuated tetravalent dengue vaccine. We evaluated the safety and immunogenicity of a single dose of TV005 across age groups in dengue-endemic Bangladesh. We performed a randomised, placebo-controlled age de-escalating clinical trial of TV005 at a single clinical site in dengue-endemic Dhaka, Bangladesh, following a technology transfer from the USA. Healthy (as determined by history, clinical examination, and safety laboratory test results) volunteers aged 1-50 years were randomly assigned 3:1 (stratified by four age groups) to receive a single dose of TV005 vaccine or placebo. Participants were followed up for 3 years. The study was double blind and was unmasked at day 180; outcome assessors, clinic staff, and volunteers remained blind throughout. Primary outcomes were safety, evaluated per-protocol as proportion of volunteers with solicited related adverse events of any severity through 28 days post dosing, and post-vaccination seropositivity by day 180 using serotype-specific neutralising antibodies (PRNT50 ≥10). Secondary outcomes included viremia, impact of past dengue exposure, and durability of antibody responses. This study is registered with Clinicaltrials.gov, NCT02678455, and is complete. Between March 13, 2016, and Feb 14, 2017, 192 volunteers were enrolled into four age groups (adults [18-50 years; 20 male and 28 female], adolescents [11-17 years; 27 male and 21 female], children [5-10 years; 15 male and 33 female], and young children [1-4 years; 29 male and 19 female]) with 48 participant per group. All participants were Bangladeshi. Vaccination was well tolerated and most adverse events were mild. Rash was the most common vaccine-associated solicited adverse event, in 37 (26%) of 144 vaccine recipients versus six (12%) of 48 placebo recipients; followed by fever in seven (5% of 144) and arthralgias in seven (6% of 108), which were only observed in vaccine recipients. Post-vaccine, volunteers of all ages (n=142) were seropositive to most serotypes with 118 (83%) seropositive to DENV 1, 141 (99%) to DENV 2, 137 (96%) to DENV 3, and 124 (87%) to DENV 4, overall by day 180. Post-vaccination, viraemia was not consistently found and antibody titres were higher (10-15-fold for DENV 1-3 and 1·6-fold for DENV 4) in individuals with past dengue exposure compared with the dengue-naive participants (DENV 1 mean 480 [SD 4·0] vs 32 [2·4], DENV 2 1042 [3·2] vs 105 [3·1], DENV 3 1406 [2·8] vs 129 [4·7], and DENV 4 105 [3·3] vs 65 [3·1], respectively). Antibody titres to all serotypes remained stable in most adults (63-86%) after 3 years of follow-up. However, as expected for individuals without past exposure to dengue, titres for DENV 1, 3, and 4 waned by 3 years in the youngest (1-4 year old) cohort (69% seropositive for DENV 2 and 22-28% seropositive for DENV 1, 3, and 4). With 3 years of follow-up, the single-dose tetravalent dengue vaccine, TV005, was well tolerated and immunogenic for all four serotypes in young children to adults, including individuals with no previous dengue exposure. National Institutes of Health-National Institute of Allergy and Infectious Diseases Intramural Research Program and Johns Hopkins University. For the Bangla translation of the abstract see Supplementary Materials section.

Evaluation of the Suppressive Capacity of Regulatory T Cells in Food Allergy Research.

Regulatory T cells (Treg) exert a crucial role in the suppression of exacerbated T helper (Th) cell responses, including those of type 2 Th (Th2) cells, and in the maintenance of tolerance to environmental antigens and food allergens. The functional capacity of Tregs to suppress Th2 responses has been studied through activation and immunosuppression assays using cells from mice and humans. The immunosuppression assay is an essential in vitro tool that allows the evaluation of the Treg capacity to limit the proliferation and expansion of conventional T cells. This approach enables the determination of the suppressive ability of different Treg subsets. In this chapter, we describe a basic and well-established immunosuppression protocol for human and murine Treg that has been widely applied in food allergy research.

Mass Cytometry in Food Allergy Research.

Mechanisms underlying food allergy are not well understood. Mass cytometry is a technique that allows the multiple analysis of cell surface markers and intracellular proteins by using the spectrum of rare metal isotopes of different atomic masses without channel overlap. Bioinformatic approaches are implemented to combine and reduce the information of more than 60 parameters to define immune cell subpopulations. To date, mass cytometry has revealed a great heterogeneity in human response to food antigens and that subpopulations of basophils and mononuclear cells might be mechanistically implicated in food allergy. This chapter reviews some fundamentals of mass cytometry and the contributions of this technique in elucidating the immune basis of food allergy, oral tolerance, food desensitization, phenotypes, and the cellular events occurring upon allergen-specific immunotherapy.

The development of Jack Jumper ant venom immunotherapy: our 25 years' experience.

Jack Jumper ant venom allergy is a uniquely Australian medical issue. The stinging ant is a leading cause of insect venom allergy in south-eastern Australia. An effective venom immunotherapy-based treatment was successfully developed by the Tasmanian Jack Jumper Allergy Research group. This paper provides a synopsis of our 25 years' research journey in developing this evidence-based treatment modality.

Standardizing In Vitro β-Lactam Antibiotic Allergy Testing with Synthetic IgE.

The global prevalence of β-lactam allergy poses a major challenge in administering first-line antibiotics, such as penicillins, to a significant portion of the population. The lack of β-lactam IgE antibody pools with defined selectivity hampers the standardization and validation of in vitro assays for β-lactam allergy testing. To address this limitation, this study introduces a synthetic IgE specific to β-lactam antibiotics as a valuable tool for drug allergy research and diagnostic tests. Using phage display technology, we constructed a library of human single-chain antibody fragments (scFv) to target the primary determinant of amoxicillin, a widely used β-lactam antibiotic. Subsequently, we produced a complete human synthetic IgE molecule using the highly efficient baculovirus expression vector system. This synthetic IgE molecule served as a standard in an in vitro chemiluminescence immunoassay for β-lactam antibiotic allergy testing. Our results demonstrated a detection limit of 0.05 IU/mL (0.63 pM), excellent specificity (100%), and a four-fold higher clinical sensitivity (73%) compared to the in vitro reference assay when testing a cohort of 150 serum samples. These findings have significant implications for reliable interlaboratory comparison studies, accurate labeling of allergic patients, and combating the global public health threat of antimicrobial resistance. Furthermore, by serving as a valuable trueness control material, the synthetic IgE facilitates the standardization of diagnostic tests for β-lactam allergy and demonstrates the potential of utilizing this synthetic strategy as a promising approach for generating reference materials in drug allergy research and diagnostics.

Preparing the Allergist/Immunologist for the Next Pandemic

The COVID-19 pandemic had a profound impact on society in general and allergists' practices in particular. The adverse effects included a loss of practice productivity and income, staffing, and in-office procedures due to concerns about the spread of infection and the need for social/physical distancing as well as isolation. Allergy training programs and research activities also suffered. Federal financial assistance, rapid adoption of telehealth with Medicare waivers, and adaptation of practice sites, training programs, and research activities allowed for some return to normal, although still with significant restrictions in staffing and in-office procedures. There were positive aspects to the pandemic in the form of telehealth initiatives, pathways for rapid development and approval of tests and treatments, opportunities for new collaborations, and expertise in vaccines. Preparation for the next pandemic needs to be considered now to avoid the mistakes and missteps that occurred with the COVID-19 pandemic. On a national level, a strategy to overcome the societal divisions, misinformation/disinformation, and distrust of science needs to be developed based on better communication, as well as advocacy for continued improvement in our public health system. Practices and training programs as well as research centers need to institutionalize changes made during the pandemic so they can quickly be reinitiated when necessary.