Search Results (67)

Background: High Mobility Group Box 1 is a mediator in inflammation, acting as a damage-associated molecular pattern molecule in various diseases. This review examines its role in nasal inflammatory disorders, such as chronic rhinosinusitis and allergic rhinitis. Methods: A comprehensive review of recent literature was conducted using a refined PubMed search strategy, focusing on studies published from 2015 onward and targeting HMGB1’s role in nasal inflammatory diseases. Results: HMGB1 emerges as a central factor in amplifying and modulating inflammatory responses through interactions with multiple receptors. It regulates cytokine production, epithelial–mesenchymal transition, and tissue remodeling, particularly in eosinophilic CRS. While discrepancies in the literature highlight its context-dependent activity, therapeutic strategies like glycyrrhetinic acid and PPAR-γ agonists demonstrate potential in modulating its effects. Conclusions: HMGB1 represents a promising diagnostic biomarker and therapeutic target in nasal inflammatory diseases. However, due to its intrinsic nature and multiple localizations, much remains to be understood. It is precisely by reflecting on its role as an “inflammatory crossroads” that we aim to underscore the need for targeted translational research to elucidate the molecular mechanisms and therapeutic applications of HMGB1. Full article

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

Objectives: Given the emerging role of peroxisome proliferator-activated receptor gamma (PPARgamma) in immune regulation and the increasing prevalence of allergic rhinitis (AR), we sought to understand how modulation of the PPARgamma pathway impacts the balance of CD4⁺ T-cell subsets, particularly regulatory T cells (Tregs) and T helper (TH)1, TH2, and TH17 cells, which are key players in the pathogenesis of AR. This knowledge is crucial for developing novel therapeutic strategies targeting the PPARgamma-CD4⁺ T-cell axis to manage AR more effectively. Methods: We used PPARgamma^f/fLyz2-Cre mice for PPARgamma deletion. In an ovalbumin (OVA)-induced AR mouse model, PPARgamma^+/-f/fLyz2-Cre mice were assessed for allergic symptoms, splenic Tregs, and nasal eosinophils. Additionally, the effects of a PPARgamma agonist on the polarization of naïve CD4⁺ T cells were examined. Results: PPARgamma^+/-f/fLyz2-Cre mice showed worsened allergic symptoms, reduced splenic Tregs, and increased nasal mucosa eosinophilic infiltration. PPARgamma agonist treatment promoted naïve CD4⁺ T-cell polarization into Tregs and inhibited their differentiation into TH1, TH2, and TH17 subsets. Conclusions: Our findings indicate that PPARgamma plays a crucial role in regulating TH-cell subsets in AR. PPARgamma agonists could be a potential therapeutic strategy to mitigate allergic inflammation in AR by promoting Treg development and suppressing pathogenic TH-cell responses. Full article

Background: Cardiovascular disorders, especially atherosclerosis, have been associated with allergic inflammation. In addition to traditional inflammatory responses, there is evidence that the development and instability of coronary artery plaque may be influenced by effector cells of allergic inflammation. This review examines the phases of allergic pathology, the immunological mechanisms of atherosclerosis, and the clinical link between allergic diseases (asthma, atopic dermatitis, allergic rhinitis, and food allergy) and cardiovascular disease (CVD), along with future therapeutic perspectives. Material and Method: A literature search was conducted in PubMed, Google scholar; ScienceDirect, Scopus, and studies published between 2014–2024 were taken into consideration. Keywords included allergic inflammation, eosinophils, mast cells, reactive oxygen species, atherosclerosis, Th2 cells, and cytokines. Epidemiological studies and review articles were included. Results: Emerging evidence suggests that allergic inflammation contributes to atherosclerosis through interconnected mechanisms such as eosinophil activation, reactive oxygen species production, mast cell degranulation, and endothelial dysfunction. Th2-driven immune responses, which are mediated by cytokines such as IL-4, IL-5, and IL-13, as well as eosinophil activity and mast cell degranulation, play a crucial role in vascular inflammation and plaque progression. Additionally, changes in lipid metabolism contribute to this process. Epidemiological studies support this connection, indicating that patients with chronic allergic conditions such as asthma, allergic rhinitis, food allergy, and atopic dermatitis experience increased cardiovascular morbidity. However, most current data are observational, and our understanding of the underlying mechanisms in humans remains limited, often relying on insights gained from preclinical models. Conclusions: A potential mechanism for cardiovascular risk is suggested by the interaction between atherosclerosis and allergic inflammation. Promising alternatives for treating allergic inflammation and cardiovascular issues include novel treatments like cytokine inhibitors, mast cell stabilizers, and biologics that target certain pathways. Further research is necessary to see whether concentrating on allergy pathways could lead to innovative treatments for cardiovascular disorders or vice versa. Full article

Background: Allergic rhinitis (AR) is triggered by immunoglobulin E (IgE)-mediated immune responses to airborne allergens. Recent studies highlight the pivotal role of T follicular helper 2 (Tfh2) cells in IgE production. Interleukin-37 (IL-37) has emerged as an intrinsic modulator of innate immunity and inflammatory processes. We aimed to investigate the regulatory effect of IL-37 on Tfh2 cells in the pathogenesis of AR. Methods: Blood samples were collected from AR patients and controls. The IL-37 levels and the frequency of Tfh2 cells were detected by enzyme-linked immunosorbent assay (ELISA) and flow cytometry, respectively. The isolated Tfh2 cells were cultured or cocultured with naive B cells. The regulatory effects of IL-37 on Tfh2/B cells were assessed using ELISA, quantitative real-time polymerase chain reaction (qRT-PCR). Mouse models of ovalbumin (OVA)-induced AR were established to explore the effect of IL-37 in vivo. Results: IL-37 suppressed the production of IL-4 and IL-21 by Tfh2 cells and downregulated C-X-C chemokine receptor type 5 (CXCR5) and B-cell lymphoma 6 protein (Bcl6) mRNA expression while upregulating B lymphocyte-induced maturation protein 1 (Blimp1) and signal transducers and activators of transduction5 (STAT5) mRNA. IL-37 decreased IgE production by B cells significantly, and the addition of anti-IL-18 receptor α alleviated this effect. In mouse models, IL-37 reduced nasal rubbing, sneezing, eosinophil counts, OVA-specific IgE, and Tfh2 proportions. Conclusions: IL-37 plays a crucial role in modulating Tfh2 cell responses in AR, suggesting a potential therapeutic target for this condition. Full article

Background/Objectives: Atopy and spondyloarthritis (SpA) are immune-mediated diseases driven by distinct T-helper (Th) cell pathways—Th2 for atopy and Th1/Th17 for SpA. The coexistence of these divergent immune responses is increasingly recognized, particularly in the context of biological therapies that target pro-inflammatory cytokines. This study aimed to investigate Th2 cytokine profiles (IL-4, IL-5, IL-13) in atopic SpA patients receiving biological therapy to better understand how such treatment may influence immune regulation in this complex clinical setting. Methods: We conducted a prospective observational cross-sectional study on 136 SpA patients stratified by biological therapy and atopy status. Serum IL-4, IL-5, and IL-13 levels were quantified using LUMINEX immunoassays. Patients were grouped into biologically treated (BT) and Bio-Naïve (BN) cohorts and further sub-categorized by atopic phenotype (allergic rhinitis, asthma, dermatitis). Statistical comparisons of cytokine levels were made using SPSS IBM version 26 to explore associations with clinical and demographic variables. Results: IL-13 levels were significantly elevated in BT-atopic patients, particularly those with allergic rhinitis and atopic dermatitis, suggesting biological therapy may modulate Th2 responses. IL-5 remained elevated in allergic asthma cases despite treatment, indicating persistent eosinophilic activity. No significant correlation was found between cytokine levels and disease duration or therapy length. Conclusions: Biological therapy in SpA may influence Th2 cytokine expression, notably IL-13, in atopic patients. These findings underscore the importance of immune profiling in guiding personalized treatment strategies and highlight the need for further investigation into the long-term immunomodulatory effects of biologics in patients with overlapping Th1/Th2-driven diseases. Full article

Background/Objectives: In recent years, there has been an increase in the prevalence of eosinophilic esophagitis (EoE), in which dysphagia is one of the main symptoms. To date, there are few data on the prevalence of EoE in pediatric patients with dysphagia. The aim of this study was to determine the causes of dysphagia in children in our region. The second aim of this study was to estimate the prevalence of EoE in children with swallowing difficulties and to see if there were differences in the characteristics of dysphagia reported by children with EoE compared to children with non-EoE-related dysphagia. Methods: The 6-year retrospective analysis included patients with dysphagia who were referred to our department. Children with dysphagia were further divided into two groups: group I consisted of children with dysphagia due to EoE, while group II consisted of children with dysphagia due to other causes (non-EoE). Results: One hundred and forty-six children between the ages 0 and 17 were enrolled into the study, including thirty-seven in group I and one hundred and nine in group II. The most common causes of dysphagia were gastrointestinal diseases, followed by neurological/psychiatric disorders. The prevalence of EoE was 25.34% in the whole study group and 41.11% considering only gastrointestinal causes of dysphagia. Children in group I were more likely to have coexisting asthma, allergic rhinitis and food allergy. There was statistically significance in higher blood eosinophil count in EoE individuals. In a multivariate binominal logistic regression model, only eosinophilia and coexisting food allergy were associated with an increased risk of EoE in patients with dysphagia. Conclusions: In our study, the most common cause of dysphagia was gastroenterological diseases, especially EoE. Patients with dysphagia, comorbid allergy and peripheral blood eosinophilia should be suspected for having EoE and referred for endoscopy. Full article

Eosinophilic esophagitis (EoE) is a chronic disease which clinically presents with symptoms related to esophageal dysfunction, while pathologically it is characterized by eosinophilic infiltration of esophageal epithelium. Most patients with EoE present with food and/or inhalant allergy symptoms. The results of animal model studies and genetic studies, as well as the efficacy of elimination diets in managing the symptoms, suggest an atopic background of the disease. The aim of this study was to evaluate the prevalence of EoE in a group of patients with upper gastrointestinal symptoms and food and/or inhalant allergies and to assess the influence of drugs used in type I allergies on the results of endoscopic, histopathological, and immunohistochemical tests. Methods: This was a prospective observational study. Patients with inhalant/food allergies and upper esophageal symptoms constituted the study group while patients without allergies who were diagnosed with dyspepsia or irritable bowel syndrome constituted the control group. All study group subjects underwent allergy testing, including prick testing and blood tests. All participants underwent a gastroscopy with specimen collection. Esophageal specimens were stained for eotaxin-1 and desmoglein-1. Results: Based on histopathology results, eosinophilic esophagitis was found in 9 of the 73 patients from the study group. All patients with EoE presented with multimorbidity and were diagnosed with at least one allergic disease in addition to EoE. Positive staining for CCL-11 was found in 56 (78%) patients in the study group, including all patients with EoE while only 3 (17%) individuals from the control group showed positive staining. The presence of DSG-1 in esophageal specimens was detected in 6 (7%) subjects from the study group in contrast to 14 (78%) subjects from the control group. DSG-1 was not found in any of the specimens of patients diagnosed with EoE. Conclusions: EoE is a rare disease, usually accompanied by allergic multimorbidity. Positive staining for eotaxin-1 and negative staining for desmoglein-1 in patients with esophageal symptoms and allergies but who did not meet EoE diagnostic criteria could be indicative of subclinical course of the disease or a masking effect of corticosteroids. It is now vitally important for both researchers and practicing clinicians to recognize that eosinophilic esophagitis (EoE) is not a homogeneous disease but rather consists of multiple subtypes (phenotypes). The so-called “classic” form of EoE—defined by current diagnostic criteria as the presence of more than 15 eosinophils per high power field on histopathological examination—appears to represent only the tip of the iceberg. There is an urgent need for further research in order to refine endoscopic techniques, expand the scope of histopathological assessments, and identify novel biomarkers to better define the distinct phenotypes of eosinophilic esophagitis. 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

The present scoping review underlines the molecular interplay between allergic rhinitis (AR), chronic rhinosinusitis with nasal polyps (CRSwNP), and interleukin-8 (IL-8). A query of PubMed database resulted in the inclusion of 34 articles in the final analysis of this scoping review. IL-8 is one interconnecting immune mediator in the physiopathology of AR and CRS. An influx of cytokines, such as interleukin (IL)-4 and IL-13, occurs from mast cells, four to six hours after the initial response signifying the development of the late-phase response allowing the entrance of eosinophils, basophils, and T-lymphocytes at the level of nasal mucosa. Chronic rhinosinusitis (CRS) is a chronic inflammatory disease that occurs in the mucosa of the nasal cavity and sinuses with two external phenotypes, but with molecular mechanisms that overlap with allergic rhinitis. Interleukin 8 induces neutrophil chemokinetic movement providing a chemotactic or directional cue. Clinical and fundamental studies established an implication of IL-8 in the disease mechanism of allergic rhinitis and CRSwNP. Moreover, there is still missing a randomized, large-cohort study with three patients groups (normal control, AR, CRSwNP) that analyzes the impact of IL-8 simultaneously. Future possible developments could focus on IL-8 as possible target for biologic treatments. Full article

Background: Emerging evidence suggests that nutraceuticals, alongside standard therapy, may benefit children with allergic rhinitis (AR). This study aimed to compare the efficacy of Quertal^® (Neopharmed Gentili S.p.A., Milano, Italy), a nutraceutical supplement based on Perilla frutescens, Quercetin, and vitamin D3, combined antihistamines per os versus antihistamines alone, in improving AR symptoms considering respiratory functional and laboratory biomarkers in pediatric age. Materials and Method: This study included 100 children, 50 in the case group (Quertal^® plus antihistamines) and 50 in the control group (antihistamines alone), with mild/moderate AR sensitized to grass pollens. They underwent assessments of respiratory function (rhinomanometry-AAR, spirometry), inflammation markers (Nasal Nitric Oxide [nFeNO]; exhaled Nitric Oxide [eFeNO]; nasal cytology), and laboratory assays (blood eosinophils, total IgE and specific IgE to Phl p1). Results: After three months of treatment, the case group showed statistically significant improvement in nFeNO and eFeNO values compared to controls (p < 0.001), as well as a reduction in nasal eosinophils (p < 0.001). Conclusions: Adding Quertal^® to standard antihistamine therapy may reduce nasal inflammation and improve AR symptoms in pediatric patients. This combination therapy shows promise as a practical, well-tolerated approach to managing AR and may have broader implications for enhancing long-term outcomes. Full article

Biologic therapies have revolutionized the treatment of severe allergic diseases, including asthma, atopic dermatitis (AD), chronic spontaneous urticaria (CSU), chronic rhinosinusitis with nasal polyps (CRSwNP), eosinophilic gastrointestinal diseases (EGIDs), and allergic rhinitis (AR). These molecularly targeted agents provide significant benefits for patients unresponsive to conventional treatments by addressing underlying immune mechanisms, particularly type 2 inflammation driven by cytokines such as IL-4, IL-5, and IL-13. Recent advancements include biologics targeting alarmins like thymic stromal lymphopoietin (TSLP) and IL-33, which may address both type 2 and non-type 2 inflammation, broadening their therapeutic scope. Despite their effectiveness, biologics remain expensive, posing socioeconomic challenges, and there are concerns regarding long-term safety and inter-individual variability in responses. Promising innovations such as bispecific antibodies and ultra-long-acting agents are under investigation, alongside digital health tools like remote biomarker monitoring and AI-driven decision support systems, which aim to enhance personalized care. However, disparities in access, particularly for underserved populations, underscore the need for policy reforms and affordable biosimilars. This review synthesizes recent findings and emerging trends, highlighting the evolving role of biologics in transforming allergic disease management and offering insights into future research directions. Full article

Nasal cytology is a non-invasive, affordable, and easily executable technique commonly used in research to study rhinitis and, to a lesser extent, chronic rhinosinusitis. It is particularly useful for the differential diagnosis of non-allergic rhinitis and for phenotyping chronic rhinosinusitis. Allergic rhinitis, asthma, and aspirin intolerance are frequent comorbidities of chronic rhinosinusitis. A diagnostic system has been proposed to assess the severity of chronic rhinosinusitis (clinical-cytological grading), incorporating nasal cytology and comorbidity observation. This score correlates with the recurrence risk of chronic rhinosinusitis with nasal polyposis. Specifically, a higher grade is often linked to asthma, aspirin intolerance, a recurrent disease requiring surgery, and a mixed cell phenotype (eosinophilic and mast cell). Although nasal cytology has been shown to be able to replace bronchial analysis with acceptable precision due to its technical characteristics, its use in diseases affecting both upper and lower airways remains limited. The main limitation of this technique is its lack of standardization, which currently hinders its widespread clinical adoption despite its increasing familiarity among allergists and otolaryngologists. In the context of the unitary airways hypothesis, nasal cytology could also provide valuable insights for managing lower airway diseases like chronic obstructive pulmonary disease and obstructive sleep apnea syndrome, which significantly impact quality of life and healthcare costs. This review aims to provide an overview of nasal cytology, highlighting its limitations and potential applications in chronic respiratory diseases. Full article

Background: Allergic rhinitis is an IgE-mediated condition of nasal congestion, runny nose, and sneezing which significantly impairs the quality of life. Current treatments, including antihistamines, often have long-term side effects, leading patients to seek safer alternatives. Objectives: Therefore, in this study, we aimed to evaluate the symptom relief efficacy of immature sword bean pod (SBP) extract, a natural material, in patients with allergic rhinitis, explore the mechanisms by which SBP regulates allergic immune responses, and evaluate its efficacy and safety as a functional ingredient in the management of allergic rhinitis. Methods: In a double-blind, placebo-controlled, randomized trial involving 64 participants with perennial allergic rhinitis, the subjects were assigned to receive either SBP or placebo orally for six weeks. Results: The SBP group exhibited significant improvements in nasal congestion (interaction p = 0.031), RQLQ (interaction p = 0.001), sleep (interaction p = 0.004), systemic reaction (interaction p = 0.002), daily life (interaction p = 0.047), and nasal symptoms (interaction p = 0.002). SBP treatment in EoL-1 and HMC-1 cells also led to a notable reduction in eosinophil cationic protein levels (p < 0.05), a key biomarker of allergic inflammation, by inhibiting PI3K/Akt/mTOR activation, resulting in decreased eosinophil activity. Conclusions: These findings suggest that the SBP extract is a promising natural treatment for allergic rhinitis, offering both efficacy and safety by improving key symptoms and reducing inflammatory responses. Full article

Background/Objectives: Histamine intolerance is becoming a critical medical problem across numerous clinical specialties, due to the absence of a standardized diagnostic and therapeutic strategy to manage patients with a suspicion of or diagnosis of this condition. Histamine intolerance is a type of non-immune food hypersensitivity, characterized by heterogenous etiologies and a very broad range of symptoms. The condition is the result of an imbalance between the amount of histamine accumulated within the body and the body’s systemic ability to degrade it. In regard to the diagnostics of histamine intolerance, the need to preliminarily exclude other potential conditions associated with increased histamine levels in the blood has been highlighted. The co-occurrence of allergies and histamine intolerance is not uncommon, and the similarity of the clinical manifestations can lead to diagnostic, as well as therapeutic, difficulties. This paper details the diagnostic and clinical workflow for a patient with histamine intolerance and polyvalent allergy comorbidity, with the aim being to help outline a protocol that may be helpful to clinicians managing patients with histamine intolerance. Case Presentation: This article presents the case of a 30-year-old patient with a polyvalent allergy and multimorbidity (allergic rhinitis, asthma, a food allergy, and eosinophilic esophagitis), with comorbid histamine intolerance. Due to the violent and severe symptoms, including facial erythema, urticaria, pruritus, abdominal pain, and tachycardia, experienced after meals, the patient received intramuscular epinephrine injections three times a week. The diagnostic protocol and the course of therapeutic management are presented. Conclusions: The diagnosis of histamine intolerance is difficult due to the high variability and heterogeneity of clinical symptoms in individual patients. Many studies on the issue recommend ruling out an allergic background in terms of the complaint. However, the possibility of the symptoms of an IgE-dependent allergy overlapping with those of histamine intolerance should be taken into account in every case. This is particularly important in patients presenting with an atypical and severe course of allergic diseases. The clinical case presented herein may be helpful for the daily practice of allergologists and physicians with other specialties, as an example of multimorbidity with both allergic and non-allergic backgrounds. Full article