Search Results (35)

Background: Differences in gene expression between inflammatory-like (iEOS-like) and resident-like (rEOS-like) eosinophil subtypes, and in eosinophil-derived serum mediators, may reflect eosinophil functional activity and their potential role in the pathogenesis of allergic asthma (AA). Methods: Twenty-three patients with non-severe AA and thirteen healthy subjects (HS) were examined. AA patients underwent a bronchial allergen challenge (BAC) with Dermatophagoides pteronyssinus and were re-evaluated 24 h later. Blood eosinophils were isolated by gradient centrifugation and magnetic separation, followed by subtyping based on CD62L expression. Gene expression was assessed by TaqMan-based quantitative PCR. Serum eosinophil cationic protein (ECP), eosinophil-derived neurotoxin (EDN), Galectin-10 (Gal10), and NADPH oxidase 2 (NOX2) were measured using ELISA. Results: Blood eosinophil subtypes from AA patients showed significantly higher expression of CLC, ECP, EPX, EDN, MBP, ALOX5, NOX2, and TGF-β1 compared to those from HS (p < 0.05), with no significant changes in LTA4H and LTC4S. iEOS-like cells in AA patients exhibited higher CLC and EPX expression compared to rEOS-like cells, (p < 0.05). Following BAC, CLC, MBP, and TGF-β1 expression increased in both eosinophil subtypes, while EPX and NOX2 increased only in iEOS-like cells (all p < 0.05). Serum ECP, EDN, and Gal10 concentrations were elevated in AA compared to HS and further increased after BAC (all p < 0.05); serum NOX2 remained unchanged. Conclusions: BAC induces a late-phase eosinophilic response in AA characterized by a partially eosinophil subtype-specific increase in gene expression and in circulating eosinophil-derived mediators. An increase in Gal10, observed at the CLC transcript level in eosinophils and in serum—but not in ECP or EDN—suggests the existence of mediator-specific mechanisms that regulate gene expression and extracellular release. Full article

Background: Acute infectious gastroenteritis (GE) and inflammatory bowel disease (IBD) may have similar clinical characteristics at onset, and discrimination between these two diagnoses can initially be challenging. Aim: To explore faecal biomarkers reflecting neutrophil, eosinophil, and epithelial activity to distinguish between acute GE and IBD onset. Methods: Faecal samples were collected from patients presenting with acute GE (n = 28), treatment-naïve patients with newly diagnosed IBD (n = 40), and healthy controls, HC (n = 40). Faecal biomarkers, including faecal calprotectin (FC), myeloperoxidase (MPO), human neutrophil lipocalin (HNL), eosinophil cationic protein (ECP), and eosinophil-derived neurotoxin (EDN), were assessed by ELISA. The Kruskal–Wallis test was used for biomarker comparisons. To evaluate the discriminative capability of biomarkers, receiver operating characteristic (ROC) curves were established. Result: Patients with acute GE displayed elevated levels of all the tested biomarkers compared with HC (p < 0.001). Higher levels of faecal HNL (p < 0.001), EDN (p < 0.01), and MPO (p < 0.05) were seen in acute GE patients than in patients with newly diagnosed IBD. HNL yielded the highest discriminative capability between acute GE and IBD with AUC 0.74, 95%CI: 0.62–0.84. Conclusions: This exploratory study suggests that faecal biomarkers may provide complementary information in the differentiation of patients with suspected acute GE and new-onset IBD. Our findings indicate that faecal HNL may have the ability to distinguish between these conditions. However, given the exploratory design and limited sample size, findings should be interpreted with caution, and the discriminative value of HNL and the other biomarkers requires further validation in larger, well-characterised acute GE cohorts. Full article

Background and Objectives: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous type 2 inflammatory disease for which biologic therapies have expanded treatment options; however, biomarkers capable of guiding biologic selection remain poorly defined. This systematic review aimed to evaluate the available evidence regarding predictive and prognostic biomarkers associated with currently available biologic agents for CRSwNP (omalizumab, dupilumab, mepolizumab, benralizumab, reslizumab, and tezepelumab). Materials and Methods: A systematic search of PubMed/MEDLINE, Embase, Google Scholar, and the Cochrane Library identified studies published between January 2006 and September 2025. Results: Twenty-five eligible studies, including 12 randomized controlled trials, 12 systematic reviews/meta-analyses, and one indirect treatment comparison study, were analyzed. Multiple biomarkers, including blood eosinophils, total IgE, periostin, eotaxins, eosinophil cationic protein, IL-5, TARC, PARC, and urinary leukotriene E4, were evaluated across biologics targeting IgE, IL-4/IL-13, and IL-5 pathways. Conclusions: Although several biomarkers reflected the modulation of type 2 inflammation and disease activity, no validated biomarker has reliably predicted the superiority of one biologic over another. Nasal IL-5 showed potential for predicting the response to anti-IL-5 therapy but requires further validation. Current evidence supports biomarker use primarily for confirming type 2 inflammation rather than guiding biologic selection. Prospective biomarker-driven and head-to-head comparative studies are needed to enable precision medicine approaches in CRSwNP. Full article

Background: The aim of this study was to evaluate the efficacy of mepolizumab as add-on therapy to intranasal corticosteroids (INCSs) for the treatment of severe, uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNPs) in a real-life setting. Methods: This prospective observational study included 60 patients with severe uncontrolled CRSwNP who received mepolizumab. Follow-up assessments were performed at baseline (T0), 3 months (T1), and 6 months (T2). At each time point, patients underwent nasal endoscopy, completed the sinonasal outcome test-22 (SNOT-22), visual analogue scales (VAS) for smell, nasal obstruction and rhinorrhoea and facial pain. Nasal secretion and blood eosinophil counts (BECs) were also evaluated. The levels of eosinophil cationic protein (ECP) in nasal secretions were measured using an enzyme-linked immunosorbent assay (ELISA). Results: Both patient- and physician-derived outcome measures showed significant improvements from baseline to 3 months, and the benefits were maintained at 6 months. No major adverse events were reported. Conclusions: Mepolizumab was associated with improvements in nasal obstruction and sense of smell, based on both patient- and physician-derived outcome measures. However, due to the single-arm design and modest sample size, these findings should be considered hypothesis-generating rather than confirmatory. Full article

Atopic dermatitis (AD) is a chronic inflammatory skin disease driven by immune dysregulation and epidermal barrier dysfunction, in which eosinophils act as key effector cells contributing to tissue damage and persistent inflammation. This comprehensive review elucidates the multifaceted contributions of eosinophils to the progression of AD. Driven by key type 2 cytokines (notably IL-4, IL-5, and IL-13) and specific chemokines, eosinophils infiltrate lesional skin and undergo IgE-mediated degranulation. The subsequent release of cytotoxic granule proteins, including major basic protein (MBP), eosinophil cationic protein (ECP), eosinophil-derived neurotoxin (EDN), and eosinophil peroxidase (EPX), directly induces keratinocyte apoptosis, exacerbates tissue remodeling, and sustains the local inflammatory cascade. Furthermore, we explore the intricate crosstalk between eosinophils and sensory neurons, which, alongside cytokines like IL-31, profoundly aggravates chronic pruritus. Consequently, modulating eosinophil activation and recruitment has emerged as a vital therapeutic approach. We systematically evaluate current and emerging pharmacological interventions, ranging from conventional topical corticosteroids to advanced targeted therapies. Particular emphasis is placed on the mechanistic impact of novel biologics and small-molecule Janus kinase (JAK) inhibitors, demonstrating how they attenuate eosinophilic inflammation. By identifying current gaps in this field, this review provides valuable insights for future research and clinical practice in the field of AD. Full article

Food-induced anaphylaxis (FIA) is a life-threatening allergic reaction, while wheat-dependent exercise-induced anaphylaxis (WDEIA) is triggered by wheat ingestion plus cofactors. To elucidate their differences, we profiled serum extracellular vesicle (EV) proteomes from 240 participants, including WDEIA, FIA, oral allergy syndrome (OAS), and healthy controls. All blood samples were obtained at least one month after the most recent acute allergic reaction, using TMT-based LC-MS/MS with ELISA validation. A total of 583 EV proteins were confidently identified, revealing distinct immune features. Compared with controls, EV-derived C1-inhibitor (C1-INH) significantly decreased in both WDEIA and FIA, showing diagnostic potential for systemic anaphylaxis. Seventy-six proteins differed between WDEIA and FIA, with reduced apolipoprotein E (APOE) in FIA and elevated eosinophil cationic protein (ECP) in WDEIA, both exhibiting good discriminatory power. These findings indicate that serum EV proteomics can reveal unique immune signatures and identify C1-INH, APOE, and ECP as potential biomarkers distinguishing food-related anaphylaxis subtypes. Full article

This study evaluated serum eosinophil cationic protein (ECP) as a biomarker for pediatric allergic airway diseases. A cross-sectional analysis was performed on children (1–17 years) with allergic asthma (AA, n = 124), allergic rhinitis (AR, n = 74), acute bronchitis (AB, n = 72), and healthy controls (HC, n = 58). Serum ECP, total IgE, eosinophil counts, allergen sensitization, and lung function were measured. Diagnostic performance was assessed using receiver operating characteristic (ROC) curves, and correlations among biomarkers were examined. Compared with HC, serum ECP levels were significantly elevated across all disease groups (AA, AR, and AB), with a particularly marked difference observed between AA and AR patients (p < 0.0001). The combination of ECP and IgE significantly improved the diagnostic accuracy for AA (AUC = 0.9494) and AR (AUC = 0.9501). Higher ECP levels were associated with increased sensitization to specific inhalant allergens and impaired pulmonary function, particularly in small airway indices. Serum ECP reflects eosinophil-mediated airway inflammation and enhances diagnostic performance for pediatric AA and AR, supporting its role as an auxiliary biomarker in evaluating pediatric allergic airway diseases. Full article

This study estimates the association between respiratory outcomes among employees of a secondary aluminum plant and airborne pollutants. Additionally, it looks into the relationship between pulmonary dysfunction in workers and X-Ray repair cross-complementing one (XRCC1) gene polymorphisms. 110 exposed workers and 58 non-exposed workers were enrolled in the study. Measurements were conducted on sulfur dioxide (SO₂), nitrogen dioxide (NO₂), and particulate particles. Pulmonary function was tested. Eosinophil cationic protein (ECP), C-reactive protein (CRP), matrix metalloproteinase-1 (MMP-1), interleukin 6 (IL6), granulocyte-macrophage colony-stimulating factor (GM-CSF), XRCC1 protein, and genotyping of XRCC1 gene polymorphisms were examined. The annual average concentrations of particulate matter (PM_2.5, PM₁₀), total suspended particulates (TSP), SO₂, and NO₂ were lower than the permissible limit. The areas around ovens, evaporators, and cold rolling mills exhibited the highest amounts. The majority of employees in these departments had impaired lung function. Prolonged exposure was associated with a significant decrease in forced expiratory volume in 1 s (FEV1%) and forced vital capacity (FVC%) among the exposed group (p = 0.001 & 0.04, respectively). Serum XRCC1 levels were significantly higher among exposed workers (p = 0.02). Inflammatory biomarkers showed no statistically significant differences between groups. Aluminum workers are at risk of developing respiratory disorders. The level of serum XRCC1 may serve as a potential biomarker for detecting susceptible workers. Full article

Asthma is increasingly recognized as a heterogeneous syndrome where traditional management fails, particularly given spirometry’s limitations in assessing small airway dysfunction. This review synthesizes the transition from clinical phenotyping to deep molecular endotyping, establishing a framework for precision medicine. We highlight the insufficiency of absolute eosinophil counts, proposing eosinophil cationic protein (ECP) and eosinophil-derived neurotoxin (EDN) as superior activation metrics. Furthermore, we explore Type 2 drivers (IL-4/IL-13, periostin) and epithelial alarmins like TSLP. Beyond classical immunology, the text describes metabolic dysregulation, specifically asymmetric dimethylarginine (ADMA) in obese-asthma phenotypes where nitric oxide synthase uncoupling promotes oxidative stress. We also analyze YKL-40 and surfactant protein D (SP-D) as markers of remodeling and barrier permeability, alongside microRNAs—specifically miR-21—in corticosteroid resistance. We conclude that managing refractory asthma requires shifting from reactive symptom control to an integrated analysis of multi-omic biomarkers. Establishing this comprehensive molecular profile via specialized centers is fundamental for addressing current diagnostic limitations, selecting biological therapies, and modifying the disease trajectory through an endotype-driven strategy addressing inflammatory, metabolic, and structural pathologies. Full article

Background: Long COVID remains a challenging and heterogeneous condition, with mechanisms that are still incompletely understood. Emerging evidence suggests that patients with allergic disease may experience more persistent post-COVID symptoms, possibly due to immune dysregulation and epithelial barrier fragility. Methods: We carried out an observational, single-center study at the Allergy and Clinical Immunology Unit of Policlinico Universitario A. Gemelli IRCCS (Rome, Italy). Seventeen adults with confirmed allergic disease and long COVID were evaluated between July and December 2024. Biomarkers reflecting allergic inflammation and barrier integrity, blood eosinophil count, total immunoglobulin E (IgE), eosinophil cationic protein (ECP), and serum free light chains (FLCs), were measured and analyzed for interrelationships and symptom correlations. Results: Participants (10 men, 7 women; mean age 43.7 years) showed variable biomarker profiles, consistent with the heterogeneity of allergic inflammation. Mean eosinophil count was 179 ± 72 cells/µL, total IgE 165.4 ± 140.6 kU/L, ECP 64.2 ± 48.5 ng/mL, and the kappa/lambda FLC ratio 1.20 ± 0.69. Notably, elevated kappa FLC levels (>19.4 mg/L) were significantly associated with high ECP (>20 ng/mL) (χ² = 10.6, p = 0.001) and increased IgE (>200 kU/L) (χ² = 6.0, p = 0.015). Individuals with higher ECP and FLCs more often reported respiratory and systemic symptoms, especially fatigue, dyspnea, and cognitive fog, that persisted beyond six months. Conclusions: These findings suggest that biomarkers of allergic inflammation and barrier dysfunction, particularly ECP and FLCs, may contribute to the persistence of long-COVID symptoms in allergic patients. The observed links between humoral activation, eosinophilic activity, and prolonged symptom burden support a model of sustained inflammation and delayed epithelial recovery. Larger, longitudinal studies including non-allergic controls are warranted to confirm these associations and to explore whether restoring barrier integrity could shorten recovery trajectories in this vulnerable population. Full article

Adipose-derived stem cells (ASCs) and their secretome have been reported to improve allergic airway inflammation. Eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP) is characterized by type 2 helper T (Th2)-diven inflammation, which shares similar mechanisms with allergic airway diseases. We assessed the immunomodulatory effects of ASC secretome on an ECRSwNP mouse model. ECRSwNP was induced by ovalbumin (OVA) and Staphylococcus aureus enterotoxin B (SEB) intranasal challenges in five-week-old BALB/c mice. To evaluate the effect of ASC secretome on eosinophilic nasal inflammation, 10 μg/50 μL of ASC-conditioned media were administered three times a week during the eight weeks. H&E and Sirius red staining were performed to evaluate the formation of nasal polyps (NPs) and the infiltration of eosinophils. The cytokine levels of interleukin (IL)-4, IL-5, IL-13, interferon-γ, IL-8, and eotaxin-1 were measured using ELISA(eBiosciences, San Diego, CA, USA). The expression levels of IL-8 and eotaxin-1 mRNA were determined by quantitative PCR. Eosinophil cationic protein (ECP) and eotaxin-1 expression were assessed by immunohistochemistry. Intranasal administration of ASC secretome significantly decreased NP-like formation and eosinophilic infiltration in the sinonasal mucosa of ECRSwNP mice. The increased IL-4, IL-5, and eotaxin-1 levels after OVA + SEB challenge remarkably decreased by ASC secretome treatment. Furthermore, ASC secretome notably decreased the gene expression of eotaxin-1 by PCR, as well as ECP and eotaxin-1 expression by immunohistochemistry. ASC secretome had immunomodulatory effects in a mouse model of ECRSwNP. Intranasal administration of ASC secretome resulted in a significant reduction in NP formation and eosinophilic inflammation through the suppression of IL-4, IL-5, eotaxin-1, and ECP. Full article

Objective: The aim of our study was to investigate whether faecal concentrations of eosinophil cationic protein (fECP) and human β-defensins (HBD2s) are significantly elevated in children with cow’s milk-protein-induced allergic colitis (MPIAP) and whether a monthly milk-free diet reduces these markers. Materials and methods: This was a single-centre, prospective, observational cohort study involving 70 infants with MPIAP, aged 1–3 months, and 30 healthy controls of the same age. The concentrations of fECP and HBD2 were measured using the ELISA method (IDK^® Eosinophil Cationic Protein and β-Defensins ELISA Kit, Immunodiagnostik AG, Germany). Diagnosis of MPIAP was confirmed with an open milk challenge test. Results: The concentrations of fECP and HBD2 proved useful in evaluating MPIAP treatment with a milk-free diet, where the resolution of allergy symptoms and a significant (p = 0.0000) decrease in the concentrations of both biomarkers were observed after 4 weeks of following the diet. The concentrations of fECP and HBD2 were still higher than those in the control group. High concentrations of fECP can be helpful in diagnosing MPIAP (100% sensitivity), but the low specificity of the assay means that there is a risk of diagnosing MPIAP in one in six children who do not have the disease. The concentrations of HBD2 have low sensitivity, so one in four children with MPIAP will not be confirmed to have the disease using this indicator. Conclusions: fECP and HBD2 can be used to monitor the resolution of colitis in infants with MPIAP treated with a milk diet, indicating a slower resolution of allergic inflammation than the resolution of allergic symptoms. Therefore, neither of the parameters are useful for the diagnosis of MPIAP. Full article

Background/Objectives: Severe asthma remains difficult to treat, even with the range of biologics we now have that target type 2 inflammation. Some patients do not respond well enough to the first biologic they try, which raises the question of whether switching to another option can help. In this study, we looked at how patients who had unsatisfactory therapeutic outcomes on other biologics responded—both clinically and at the biomarker level—after switching to dupilumab. Methods: We reviewed data from the Allergy and Clinical Immunology Unit of Fondazione Policlinico Universitario A. Gemelli-IRCCS, Rome, Italy, between January and June 2025. The study included fifteen adults with uncontrolled severe asthma who had previously been treated for at least six months with benralizumab, omalizumab, or mepolizumab before switching to dupilumab. We evaluated demographic, clinical and laboratory data. Lung function (Forced Expiratory Volume in 1 s (FEV₁)), blood eosinophils, total and specific IgE to staphylococcal enterotoxins, eosinophil cationic protein (ECP), free light chains (FLC), and FeNO were assessed at the time of the switch and again after 12 months. Comparisons were made using paired tests, and a p-value < 0.05 was considered statistically significant. Results: After a year on dupilumab, we saw clear improvements: mean FEV₁ went up by about 10.8% predicted (p = 0.002), FeNO dropped by an average of 22 ppb (p = 0.005), blood eosinophils fell by roughly 400 cells/µL (p = 0.003), and ECP levels decreased by 13 µg/L (p = 0.009). Kappa FLCs also showed a significant drop (p = 0.04). Clinically, 40% of patients met criteria for a meaningful response, and 20% achieved complete remission. Dependence on oral corticosteroids was notably reduced. Baseline levels of eosinophils, ECP, IgE, and FLCs correlated with response to treatment. Conclusions: Our study, despite the small sample size, highlights that in patients with severe asthma who do not show a good response to their first biologic, switching to dupilumab can lead to significant improvements. Markers of type 2 inflammation at baseline might help predict who benefits most. Larger, multi-center, prospective studies are needed to confirm these results. 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

Epithelial barrier damage plays a central role in the development and maintenance of allergic inflammation. Rises in the epithelial barrier permeability of airways alter tissue homeostasis and allow the penetration of allergens and other external agents. Different factors contribute to barrier impairment, such as eosinophilic infiltration and allergen protease action—eosinophilic cationic proteins’ effects and allergens’ proteolytic activity both contribute significantly to epithelial damage. In the airways, allergen proteases degrade the epithelial junctional proteins, allowing allergen penetration and its uptake by dendritic cells. This increase in allergen–immune system interaction induces the release of alarmins and the activation of type 2 inflammatory pathways, causing or worsening the main symptoms at the skin, bowel, and respiratory levels. We aim to highlight the molecular mechanisms underlying allergenic protease-induced epithelial barrier damage and the role of immune response in allergic asthma onset, maintenance, and progression. Moreover, we will explore potential clinical and radiological biomarkers of airway remodeling in allergic asthma patients. Full article