Allergies

Background/Objectives: Toxocara spp. infection has been associated with severe asthma and allergic manifestations due to the activation of eosinophils by the release of Th2 cell cytokines. The aim of this study was to investigate the association between Toxocara spp. infection and eosinophil levels in severe asthmatic patients. Methods: The socio-demographic, peripheral blood eosinophils counting total IgE, sIgE to aeroallergens and FEV1 results were acquired from the Program of Asthma and Rhinitis Control (ProAR) at the Salvador–Brazil databank; IgG anti-Toxocara spp. levels were measured in 176 severely asthmatic patients by indirect ELISA. Results: The Toxocara spp. seroprevalence was 50.6%. Eosinophilia was present in 54% of the population. The correlation between IgG anti-Toxocara spp. levels and eosinophils levels was positive. Eosinophilic individuals with SPT, sIgE for D. pteronyssinus, D. farinae and B. tropicalis showed positive results; IgE ≥ 160 UI/dL and uncontrolled asthma presented more positive results for IgG anti-Toxocara spp. Conclusions: Our findings suggest that eosinophil levels are influenced by the presence of IgG antibodies against Toxocara spp. Additionally, helminth infection may modulate immunological responses in allergies and uncontrolled asthma, which could help explain the exacerbation of asthma symptoms. Full article

Allergic diseases, particularly respiratory allergies like asthma and allergic rhinitis, are a growing public health concern influenced by environmental factors such as climate change and air pollution. The exposome framework enables a comprehensive assessment of how lifelong environmental exposures shape immune responses and allergic sensitization. Peru’s diverse ecosystems and climates provide a unique setting to investigate regional variations in allergic sensitization. This study characterized these patterns in five Peruvian regions with distinct climatic, urbanization, and socioeconomic characteristics. A total of 268 individuals from Lima, Piura, Tarapoto, Arequipa, and Tacna were analysed for allergen-specific IgE responses using a multiplex IgE detection system. The results revealed significant geographical differences in sensitization frequencies and serodominance profiles, based on descriptive statistics and supported by Chi-square comparative analysis. House dust mites were predominant in humid regions, while Arequipa exhibited higher sensitization to cat allergens. In Tacna, olive pollen showed notable prevalence alongside house dust mites. Tarapoto’s high humidity correlated with increased fungal and cockroach allergen sensitization. Notably, some allergens traditionally considered minor, such as Der p 5 and Der p 21, reached sensitization prevalences close to or exceeding 50% in certain regions. These findings provide the most detailed molecular characterization of allergic sensitization in Peru to date, highlighting the importance of region-specific allergy management strategies. Understanding environmental influences on allergic diseases can support more effective diagnostic, therapeutic, and preventive approaches tailored to diverse geographical contexts. Full article

Affecting around 30–40% of the population worldwide, allergic disorders including asthma, rhinitis, eczema, and food allergies, are relatively common. Environmental factors, such as air pollution and climate change, which aggravate allergic reactions, contribute to the growth of these diseases. Although conventional treatments such as antihistamines and immunotherapy remain the standard for symptom management, growing interest in natural remedies highlights the potential value of medicinal plants as complementary therapies. Commonly present in plants, vitamins and antioxidants have strong anti-inflammatory and antioxidant actions that can control immune responses, lower oxidative stress, and thus reduce inflammation, which is the main element in allergic reactions. By focusing on the fundamental causes of inflammation and immunological dysregulation, phytochemicals have shown encouraging effects in reducing allergic symptoms. This review investigates the role of plant flavonoids, polyphenols, and vitamins in lowering allergic symptoms and inflammation, and suggests their potential in allergy management. It also aims to provide a short review of various plant species that are used in folk medicine for allergy treatment. The inclusion of plant-based compounds in allergy therapy could provide more complete and environmentally friendly remedies to enhance patients’ quality of life. Full article

Purpose: This study aimed to evaluate the immunological response to the 23-valent pneumococcal polysaccharide vaccine (PPV23) in patients investigated for immunodeficiencies due to recurrent infections at EPM-UNIFESP Clinical Immunology outpatient clinic. Methods: This is a longitudinal retrospective study. Data were collected from the medical records of patients between 2012 and 2020. The analyses were developed in two stages: before and after administration of the PPV23 vaccine. Results: A total of 390 patients who received the PPV23 vaccine were selected. Among those who demonstrated an adequate serological response (63.6%), there was a notable decrease in the risk of upper respiratory tract infections (URTI) by 66%, tonsillitis by 74%, otitis by 76%, sinusitis by 49%, and uncomplicated pneumonia (PNM) by 77%. For invasive infections, the risk reduction was 95% for pneumonia with parapneumonic effusion and 93% for meningitis. Conclusions: The study demonstrated a significant decrease in the risk of bacterial infections following the administration of the PPV23 vaccine in this population. Therefore, we recommend including PPV23 in the vaccination schedule following pneumococcal conjugated vaccines for patients with recurrent pneumococcal infections to enhance protection and avoid complications. Full article

Hidradenitis suppurativa (HS) and atopic dermatitis (AD) are both inflammatory dermatoses that can significantly impact patient quality of life, however, limited research exists regarding their association. The purpose of this comprehensive review is to compare the inflammatory pathogenesis of HS and AD, explore the associations between these diseases, and discuss standalone and concomitant disease treatment options. Although HS and AD are understood to be primarily driven by the Th1 and Th2 inflammation pathways, respectively, these conditions both utilize the Janus Kinase/Signal transducer and activator of transcription (JAK/STAT) pathway to promote inflammation. Newer research also suggests that IL-36 and IL-1 receptor-associated kinase 4 (IRAK4) may be two additional inflammatory signals shared between the HS and AD disease pathways. These shared mechanisms are reflected in patient presentations as HS and AD are often concomitantly present and demonstrate a bidirectional association in the current literature. Treatment options for concomitant disease are limited, but leverage the shared immune pathogenesis of both diseases. Dupilumab has been reported to improve both HS and AD symptoms in select patients. JAK inhibitors are currently FDA-approved for the treatment of AD, and early trials have suggested benefits from JAK inhibitors such as upadacitinib, povorcitinib, and topical ruxolitinib for HS. Possible future avenues for research on treating both HS and AD include IRAK-4 inhibitors such as zabedosertib and BAY1830839, and diet and gut microbiome modifications. Full article

Psoriasis is a chronic inflammatory autoimmune disease primarily affecting the skin and, in some cases, the joints, and is characterized by erythematous, scaling lesions. Building up the doses has been conventional, but many patients will not obtain good results and a new, more targeted therapeutic strategy is desired. In the past few years, immune checkpoint inhibitors have revolutionized moderate to severe psoriasis management by blocking crucial pro-inflammatory cytokines, introducing new avenues for biological therapies. This review summarizes recent developments in biological therapies, including their mechanisms of action and clinical efficacy. While bimekizumab, an IL-17A and IL-17F inhibitor, strongly suppresses inflammation, selective inhibition of the IL-12/23 pathways is targeted with the small molecule TYK2 inhibitor deucravacitinib. For example, spesolimab, an inhibitor of IL-36 signaling, is being investigated for generalized pustular psoriasis. In this respect, new therapies provide better efficacy and quality of life, target specific psoriasis subtypes, and are safer and more effective than anti-inflammatory treatments. Such therapies could radically inform the standards of care, and the long-term safety and patient-centered outcomes of these innovative strategies will be the subject of continued research. Full article

The interplay between allergic diseases and neurological disorders has gained increasing attention over the past decades, highlighting potential shared pathophysiological pathways. Allergic diseases, including asthma, eczema, and allergic rhinitis, are characterized by chronic inflammation and immune dysregulation, which may impact the pathogenesis of certain neurological conditions. Emerging evidence suggests that conditions such as multiple sclerosis (MS), migraine, epilepsy, neurodegenerative diseases, and neurodevelopmental disorders may be influenced by systemic inflammation and altered immune responses associated with allergies. The purpose of this paper is to provide an overview of current epidemiological evidence suggesting a relationship between allergic and neurological diseases. Understanding the complex interactions between allergic and neurological diseases could provide new insights into their aetiology and reveal novel therapeutic targets, paving the way for integrated approaches in managing comorbid allergic and neurological conditions, ultimately improving patient outcomes and quality of life. Full article

Esophageal fibrotic remodeling is a major complication of chronic inflammation in eosinophilic esophagitis (EoE) and represents one of the main determinants of symptoms in adult patients with EoE, with a remarkable impact on patients’ quality of life and the healthcare system. Esophageal fibrotic remodeling is diagnosed through upper gastrointestinal endoscopy, radiological studies, and a functional luminal imaging probe. However, diagnostic underestimation of esophageal strictures and suboptimal adherence to EoE guidelines still represent limitations of current clinical practice. Combined with medical therapy and/or elimination diets, endoscopic dilation remains the cornerstone treatment for esophageal strictures and rings, offering a safe and effective option for managing obstructive symptoms. Different modalities are available for esophageal endoscopic dilation of EoE, including mechanical and balloon dilators. Mechanical dilators provide tactile feedback during the procedure and exert longitudinal and radial forces. In contrast, balloon dilators apply a purely radial force and enable direct visualization of the esophageal mucosa during the procedure. Both mechanical and balloon dilators are safe and effective, with no single modality demonstrating clear superiority. Consequently, the choice of dilation technique is guided by stricture characteristics, the expertise of the endoscopist, and considerations related to the financial and environmental sustainability of the devices. This review aims to summarize the most relevant evidence on the endoscopic evaluation and dilation of fibrostenotic complications in EoE, also providing practical guidance for clinicians to optimize the endoscopic management of these patients. Full article

Allergic rhinitis and asthma are significant public health concerns worldwide. While previous studies have explored how nasal and buccal bacteriotas influence these conditions, few have directly compared their bacteriomes within the same cohort. To bridge this gap, I analyzed 16S rRNA next-generation sequencing data from 347 individuals, including participants with allergic rhinitis, asthma and healthy controls. The nasal and buccal bacteriomes shared all dominant bacterial taxa but differed significantly in their phylum- and genus-level relative abundances. Alpha-diversity was significantly higher in the buccal cavity, while beta-diversity varied significantly across all indices and clinical groups. Over 80% of the predicted metabolic pathways were differentially regulated between the two cavities, yet these functional differences remained fairly consistent across clinical groups. Naso-buccal bacterial networks exhibited striking differences in structure, complexity and hub nodes. Notably, the network of healthy controls showed a clear segregation between nasal and buccal bacteria, with 93.5% of the interactions occurring within each respective cavity, and contained few pathogenic keystone taxa. In contrast, bacterial networks from diseased individuals exhibited reduced ecological specialization and more pathogenic keystone taxa linked to airway disease. These findings, thus, demonstrate that the naso-buccal bacteriome plays distinct yet interconnected roles in allergic rhinitis and asthma. Full article

Population growth and the depletion of natural resources have driven the incorporation of edible insects into the human food matrix. Despite their high nutritional value and the environmental benefits of insect farming compared to conventional protein sources, their consumption poses potential risks, including food allergies. Sensitization to insect allergens can occur through various exposure routes, with cross-reactions involving other foods and environmental allergens being well-documented. Vulnerable groups such as children and the elderly may have increased susceptibility not only because of genetic predisposition but also because of age-related physiological factors. This review explores the emerging risks of edible insect consumption, with a focus on children and the elderly. Age-related alterations in the gut microbiota, digestion, immune function, and overall physiology can facilitate the absorption of intact allergenic proteins and impair immune responses. Furthermore, the allergenic potential of insect proteins and their associated microbiota remains poorly characterized. Limited research exists on the effects of processing methods on these proteins. Consequently, incorporating edible insects into food products could present an additional allergenic risk, particularly for these vulnerable populations. Understanding these risks is essential for ensuring the safety and acceptance of edible insects as sustainable food ingredients. Full article

Pediatric asthma is the most common chronic childhood disease in the US and a major public health concern. It is considered to comprise multiple clinical variants or phenotypes with different etiologies and pathophysiologies. Former research has shown that airway bacteriomes vary in composition and structure across pediatric asthma phenotypes, but their functional diversity and bacterial interactions have hardly been investigated. A previous study of 163 children from Washington DC identified three statistically different asthma phenotypes, each with a unique nasopharyngeal bacterial composition and diversity. Here, I reanalyze 16S rRNA high-throughput sequences from the same cohort to characterize their bacterial metabolism and interactions. I detect 61 to 102 metabolic pathways (PICRUSt2; q ≤ 0.05) differentially expressed across the three asthma phenotypes. Most of those pathways are related to biosynthesis and degradation processes and statistically (p ≤ 0.0012) separated the three clinical groups. Co-occurrence networks also differ in connectivity across phenotypes, suggesting unique bacterial interactions in each group. Five to eight keystone taxa are detected across phenotypes. Insights from this and previous studies, hence, confirm the airway bacteriome heterogeneity across pediatric asthma, increasing our understanding of its etiology and pathophysiology, and provide new taxonomic and functional biomarkers of disease for targeted interventions and therapies. Full article

Introduction: Allergic rhinitis (AR) is largely driven by IgE-induced immune cell activation, which promotes allergen-induced upper airway inflammation. The regulatory mechanisms of IgE synthesis in AR are poorly understood. Several analyses associate single nucleotide polymorphisms (SNPs) which reduce the expression of the D2HGDH gene with AR. D2HGDH encodes an enzyme that converts D-2-hydroxyglutarate (D2HG) to α-ketoglutarate (α-KG). This study aims to clarify the relationship between AR and SNPs in D2HGDH. Methods: Mice were treated with vehicle control or octyl-D2HG prior to intranasal exposure to Alternaria alternata. Draining lymph nodes (dLNs) were then evaluated for IgE-producing cells and T-cell polarization. Next, mice were exposed to intranasal Alternaria on days 0, 10, 20, and 27–30 and were treated intranasally with octyl-D2HG or vehicle control on days 20 and 27. Nasal inflammation was analyzed in nasal lavage fluid (NLF) cellularity and antigen-specific IgE production. Results: The administration of D2HG prior to Alternaria exposure suppressed IgE synthesis (p < 0.01) and Th2 cell polarization (p < 0.01) in dLNs. In a murine model of AR, D2HG administration reduced overall cellular infiltrates and eosinophils in NLF. Further, antigen-specific IgE in NLF was significantly reduced in mice treated with D2HG (p < 0.05). Conclusions: An analysis of the regulatory landscape surrounding the rs34290285 SNP demonstrates that the downregulation of D2HGDH expression reduces the risk of AR. Downregulation of D2HGDH likely results in accumulation of D2HG intracellularly, suggesting that D2HG is protective against allergic rhinitis. We show that the administration of D2HG impairs IgE production, leading to the amelioration of allergic sinonasal inflammation in a murine model of AR. These findings suggest a causal relationship between D2HGDH expression, D2HG levels, and allergic rhinitis risk. Full article

Worldwide, cat allergies affect 15% of the population. Cat allergens are ubiquitous and challenging to eliminate from homes, making it difficult to implement effective allergen reduction strategies. Developing strategies to reduce cat allergens in homes could alleviate the burden of allergic diseases, enhance symptom management, lower healthcare expenses, and improve patients’ quality of life. Studies have produced varied results concerning the effectiveness of specific environmental control measures in lowering cat allergen levels and improving clinical outcomes for allergic diseases. This review evaluates the existing evidence on the effectiveness of environmental control measures in reducing cat allergens and their potential clinical impact. Full article

Peanut allergies, driven by sensitization to key allergens Ara h1, Ara h2, and Ara h3, present significant health risks, particularly in food processing and consumer settings where accidental exposure is frequent. To mitigate this risk, we developed AYA22AR321, a novel aptamer with selective, high-affinity binding to these allergens (Kd values: 0.5 nM for Ara h1, 14.5 nM for Ara h2, and 6.6 nM for crude peanut extract). Functional assays using RBL-2H3 (rat basophilic leukemia cell line) cells showed that AYA22AR321 significantly reduces IgE-mediated degranulation, indicating its potential to attenuate allergic responses. To translate these findings into practical use, we formulated an allergen-neutralizing spray, FISTOQ, containing AYA22AR321, which effectively neutralized peanut allergens on peanut-butter-contaminated surfaces. Stability tests confirmed that FISTOQ, comprising eco-friendly surfactant and preservative, maintains its allergen-neutralizing efficacy over time. Comprehensive safety assessments, including immunogenicity, cytotoxicity in human PBMCs, and mutagenicity via the Ames test, demonstrated that AYA22AR321 is non-immunogenic, non-cytotoxic, and non-mutagenic. This study establishes AYA22AR321 as a promising, targeted strategy for allergen control, providing a significant advancement in allergen mitigation and food safety for high-risk environments. Full article

(1) Background: Allergic disorders and systemic lupus erythematosus (SLE) are immune dysregulation conditions that are increasingly prevalent, with growing evidence suggesting shared pathogenesis. (2) Results: Patients with SLE have a higher risk of allergic conditions, particularly allergic rhinitis and asthma; notably, children born to mothers with SLE show an increased asthma risk. This association appears linked to shared mechanisms involving T-helper 2 cells, IgE, human leukocyte antigen, genetic factors, and environmental triggers. Various medications used in allergic disorders and SLE have benefits in both diseases. Many SLE medications benefit allergic dermatitis. Meanwhile, omalizumab used for severe asthma may reduce SLE activity. (3) Conclusions: More research is essential to clarify the shared pathways and cross-benefits of treatments for allergic disorders and SLE. Novel treatment strategies are warranted to clarify the roles of biologic treatment in allergic disorders in the setting of SLE. Full article

Background: Atopic dermatitis (AD), allergic rhinitis (AR), and chronic rhinosinusitis with nasal polyps (CRSwNP) represent interconnected conditions within the spectrum of type 2 inflammatory diseases. While these conditions share common genetic and epigenetic pathways, the precise molecular mechanisms remain underexplored. Methods: This review integrates the latest insights on the genetic and epigenetic factors linking AD, AR, and CRSwNP, focusing on genome-wide association studies, DNA methylation patterns, histone modifications, and microRNA regulation. Results: In all three conditions, epigenetic modifications, including DNA methylation (Me) and histone acetylation (Ac) and methylation, regulate inflammatory and barrier-related genes, influencing disease severity. Notably, miRNAs such as miR-146a and miR-155 play pivotal roles in modulating inflammation across all three diseases, while disease-specific miRNAs contribute to airway remodeling (miR-125b and miR-21 in AR and CRSwNP). Emerging evidence underscores the role of microbiome-driven inflammasome activation and matrix metalloproteinases (MMP-2, MMP-9, and MMP-12) in perpetuating chronic inflammation and remodeling. Conclusions: The interplay between genetic predispositions, epigenetic modifications, and exposomal factors underscores the systemic nature of type 2 inflammation. A deeper understanding of these interconnected mechanisms could lead to transformative, personalized diagnostic and therapeutic advancements. Full article

Background: Tree nut allergy affects approximately 1% of the U.S. population and the prevalence is increasing. Walnut allergy is the most commonly reported tree nut allergy in the United States. This study aimed to investigate the IgE cross-reactivity between walnut allergen Jug r 4 and peanut allergen Ara h 3 in individuals with dual walnut and peanut allergies. Methods: Jug r 4 was purified from whole walnut extract and analyzed via western blot using anti-Ara h 3 antibodies alongside serum IgE from walnut allergic patients. Sera from individuals allergic to both peanuts and walnuts were utilized to examine peptide microarrays comprising synthetic overlapping 15 mer peptides, offset by five amino acids, of Ara h 3 and Jug r 4. These results were compared against computationally predicted IgE epitopes using the Structural Database for Allergic Proteins (SDAP). Additionally, SWISS-MODEL protein modeling software was employed to map IgE epitopes onto Ara h 3 and Jug r 4. Results: Our findings revealed previously unreported IgE epitopes for dual-allergic sera within both allergens, highlighting the locations of empirically determined and SDAP-predicted IgE epitopes. Conclusions: While six epitopes were predicted as cross-reactive, only three were frequently recognized by IgE in dual-allergic individuals, underscoring their potential significance in clinically relevant cross-reactivity. Full article

In Switzerland, only scarce data are available on the prevalence and treatment of allergic rhinitis. Although the presence of AR symptoms in temporal relation to the respective aeroallergen is indicative, still a substantial number of affected individuals are deemed underdiagnosed and potentially undertreated. A national online survey was conducted for consecutive participants with AR symptoms in medical practices irrespective of diagnosis, therapy, or the reason for the visit. Univariate and multivariate regression analyses were performed, as well as multiple correspondence analysis for participants with allergic rhinitis diagnosis (ARwD) and without diagnosis (ARwoD). A total of 392 of 637 participants with rhinitic symptoms self-reported an AR diagnosis with a symptom onset more than 5 years ago in 74%. Despite treatment, up to one-third of participants with ARwD had persistent severe symptoms. Asthma was reported more frequently in participants with ARwD (148/392) than with ARwoD (26/245), (42% vs. 12%, p < 0.001, q < 0.001). Allergologists were consulted more often by participants with ARwD (106/392; 30% vs. 3/245; 2%), while more participants with ARwoD visited pharmacies for treatment advice (40/392; 11% vs. 57/245; 40%). The coexistence of AR and asthma with severe symptoms is a specific phenotype with difficult to treat nasal symptoms, amongst others. Hence, appropriate diagnosis and treatment of suspected and diagnosed AR should be prioritized, especially, but not limited to, patients with AR and asthma. Full article

Regulatory T cells (Tregs) play a central role in immune regulation and tolerance. The transcription factor FOXP3 is a master regulator of Tregs in both humans and mice. Mutations in FOXP3 lead to the development of IPEX syndrome in humans and the scurfy phenotype in mice, both of which are characterized by fatal systemic autoimmunity. Additionally, Treg dysfunction and FOXP3 expression instability have been implicated in nongenetic autoimmune diseases, including graft-versus-host disease, inflammatory bowel disease, rheumatoid arthritis, and multiple sclerosis. Recent investigations have explored FOXP3 expression in allergic diseases, revealing Treg alterations in food allergies, asthma, and atopic dermatitis. This review examines the multifaceted roles of FOXP3 and Tregs in health and various pathological states, including autoimmune disorders, allergic diseases, and cancer. Additionally, this review focuses on the impact of recent technological advancements in facilitating Treg-mediated cell and gene therapy approaches, including CRISPR/Cas9-based gene editing. The critical function of FOXP3 in maintaining immune homeostasis and tolerance to both self-antigens and alloantigens is emphasized. Considering the potential involvement of Tregs in allergic diseases, pharmacological interventions and cell-based immunomodulatory strategies may offer promising avenues for developing novel therapeutic approaches in this field. Full article