Search Results (234)

Atopic dermatitis (AD) is increasingly interpreted through frameworks emphasizing barrier dysfunction, type 2 cytokine signaling, pruritus pathways, and microbial dysbiosis, often relegating IgE-mediated mechanisms to secondary roles. In this narrative review, we synthesize historical, clinical, immunologic, and histopathologic evidence to propose a conceptual model in which IgE-bearing antigen-presenting cells (APCs)—including Langerhans cells, inflammatory dermal dendritic cells, and inflammatory dendritic epidermal cells (IDECs)—participate in an IgE-dependent amplification loop that may contribute to the chronicity of extrinsic (IgE-associated) AD. Evidence from human studies indicates that FcεRI-expressing APCs can acquire environmental allergens through IgE, enhancing antigen uptake and T-cell activation, while mast cells and basophils further reinforce type 2 inflammation through IgE-dependent and IgE-augmented pathways. Although these mechanisms have been described across distinct experimental and clinical contexts, their integration into a unified pathogenic circuit remains hypothesis-driven. We therefore present an interpretive framework that organizes these partially validated mechanisms into a coherent model linking cutaneous sensitization, allergen capture, APC activation, Th2 polarization, and spongiosis formation. This conceptual synthesis aims to reposition IgE-mediated processes within the broader pathophysiology of extrinsic AD and to highlight potential therapeutic implications for targeting IgE–FcεRI signaling and IgE-dependent APC biology. Full article

The hallmarks of allergic diseases are Type 2 immunity, including IL-4 and IL-13 production, IgE antibody generation, mast cell and basophil activation, histamine release, and eosinophil activation. There are many routes by which such mediators can influence CNS biology, including cytokine entry or signaling via brain barrier receptors; leukocyte trafficking across activated barriers; cytokine signaling via circumventricular organ sites or dural immune compartments; vagus nerve afferent signaling; mast cell degranulation; and histamine neuromodulation. Neuroinflammation is a common hallmark of many neurodegenerative diseases, but whether and to what degree allergic/type 2 immune biology may be involved depends on the specific disease stage and pathology. Here, we assess studies connecting the roles of IL-4/IL-13 signaling, IgE/mast cell activation, eosinophil-attractive chemokines, and histamines in Parkinson’s disease, Alzheimer’s disease, multiple sclerosis, amyotrophic lateral sclerosis, dementia with Lewy bodies, Huntington’s disease, prion disease, and tauopathy/atypical parkinsonism. Mechanisms appear most clear in the case of Parkinson’s disease, where epidemiology suggests an important role in dementia/Alzheimer’s disease, while for other neurodegenerative conditions the evidence is less compelling and may be either mechanistic or modulatory. Confounding issues include sex differences, drug exposures, comorbid conditions, socioeconomic factors, and coexisting inflammatory diseases. Finally, we suggest a strategy based on longitudinal immune phenotyping, CNS biomarkers, and pathway manipulation to assess the relationship between allergic immune signaling and neurodegeneration. Full article

Background/Objectives: The increasing use of pea protein in plant-based foods raises concerns about IgE-mediated reactions, particularly in individuals sensitized to peanut. Knowledge on clinically relevant pea allergens and the impact of heat processing remains limited. This study investigated how thermal treatment affects the IgE binding and functional allergenicity of pea proteins in children with a confirmed pea allergy, with or without a concomitant peanut allergy. Methods: Serum from 11 patients was analyzed using SDS-PAGE, Western blotting, and an indirect basophil activation test (iBAT). Results: All patients showed IgE binding to Pis s 1 and PA2a/b in raw pea extract, with variable sensitization to Pis s 2 and mitogenic lectin. Heating (120 °C, 5 min) markedly reduced IgE binding and eliminated detectable IgE to Legumin S and ML. Despite this reduction, basophil sensitivity did not decrease; in several patients, EC50 values significantly decreased, indicating increased basophil responsiveness to heated pea. Patients with IgE profiles dominated by Pis s 1 and PA2a/b were most likely to show enhanced basophil activation after heating. Conclusions: These findings demonstrate that heat-stable vicilin subunits and albumins can maintain functional allergenicity despite reduced IgE recognition, underscoring the need for diagnostic approaches that incorporate processed food allergens. Full article

Interleukin-5 (IL-5) has long been positioned as a lineage-restricted cytokine primarily responsible for eosinophil differentiation and survival. However, emerging mechanistic and clinical evidence supports a broader conceptual shift: IL-5 should no longer be viewed solely as an eosinophil growth factor, but as a context-dependent regulator embedded within dynamic airway immune networks. Drawing on advances in eosinophil subset biology, receptor signaling, and tissue-level immune crosstalk, this review reframes IL-5 biology through the lens of systems-level inflammatory regulation across airway and systemic eosinophilic diseases. Recent data reveal functional heterogeneity between resident and inflammatory eosinophil subsets, challenging the assumption that blood eosinophilia uniformly reflects pathogenic activity. In parallel, functional IL-5 receptor expression has been identified on multiple structural and immune cell populations—including epithelial cells, mast cells, plasma cells, basophils, neutrophils, and fibroblasts—supporting a broader tissue-signaling paradigm. Experimental and translational studies further link IL-5 to epithelial integrity, airway remodeling, and mucus pathology, suggesting structural and network-level effects beyond simple eosinophil depletion. Comparative analyses across asthma, chronic rhinosinusitis with nasal polyps, and COPD demonstrate that eosinophilic inflammation is biologically heterogeneous and context-dependent. While IL-5-targeted therapies yield consistent benefit in severe asthma, therapeutic responses in other airway diseases appear to be shaped by local tissue architecture and mixed inflammatory programs. Together, these observations illustrate a paradigm shift from pathway-specific inhibition toward network-informed disease control and highlight key areas for future mechanistic investigation. Full article

Pregnancy loss affects ~15% of couples and often results from embryonic chromosomal abnormalities. Early peripheral biomarkers that signal abnormal development could improve counseling and clinical decision-making. Here, we analyzed early-pregnancy peripheral blood from patients who conceived via assisted reproduction without preimplantation aneuploidy testing. Samples were collected ≤12 weeks’ gestation for complete blood counts with differentials and multiparameter flow cytometry to quantify major lymphocyte subsets (total T, B, cytotoxic T cells, T helpers (Th), Th1, Th2, Th9, Th17, and regulatory T cells (Treg)). Participants were followed until pregnancy resolution (live birth, euploid or aneuploid miscarriage), and immune profiles were compared by outcome using the Kruskal–Wallis test. Exploratory discriminative analyses were performed with significantly different immune cell quantities. Basophils were highest in the aneuploid miscarriage group (n = 26), distinguishing them from both euploid miscarriage (n = 27) and live birth (n = 91). Th9 cells were lower in aneuploid miscarriages compared to euploid miscarriages. Th17 levels were higher in live births compared with both miscarriage groups. Additional aneuploidy-type-specific immune differences were observed. These alterations may reflect maternal immune recognition of a non-viable conceptus and localized immune activation at the fetal–maternal interface. If validated in larger cohorts, these early peripheral markers may help identify pregnancies at risk for miscarriage, particularly those involving chromosomal abnormalities. Full article

Having appropriate and meaningful diagnostic procedures is crucial in the approach to patients with chronic spontaneous urticaria (CSU), so we wanted to investigate relationships between CSU patients’ common serum factors and clinical CSU features, and their temporal trends during antihistamine treatment. In this exploratory hypothesis-based study, we assessed disease severity and quality of life (QoL) in, initially, 41 CSU patients using UAS7, daily UAS, UCT, DLQI, and CU-Q2oL. Concurrently, we measured serum complete blood count (CBC), total IgE, thyroid antibodies and hormones, ANA, D-dimer, vitamin D, and the inflammatory molecules CRP, ESR and IL-6. We compared initial (T1) and follow-up findings (T2) (after 3 months of antihistamine therapy). Basophil concentration was the only examined serum factor useful in assessing current CSU severity/daily UAS (sensitivity 78.6%; specificity 63%; p = 0.028). Basopenia was more frequent in patients with moderate/severe CSU than in those with mild disease or remission, as measured by daily UAS (79% vs. 37%; p = 0.020). T4 values showed a significant dependence on CSU duration (r = −0.328; p = 0.036). ESR was the only examined serum factor significantly associated with weekly CSU severity (UAS7) (p = 0.038). Antihistamine treatment significantly reduced CSU activity (recorded by daily UAS and UAS7) and improved QoL (DLQI) (p = 0.006) and disease control/UCT (p = 0.005). After three months of treatment, only the CRP value correlated with CSU control/UCT (p = 0.014). We encourage the use of diagnostics employing basophil counts and clinical indices UAS7, daily UAS, UCT and DLQI for insight into a patient’s CSU clinical condition. Serum factor values did not change during the 3-month treatment period, so it is not useful to measure them repeatedly. Although this study involved a small cohort and has many limitations, these promising results highlight the need for replication with a greater number of CSU patients. Full article

Peanut allergy (PA) remains a major diagnostic challenge in pediatric allergy, largely due to the frequent discrepancy between immunological sensitization and clinically relevant disease. This study aimed to develop a real-life diagnostic prediction model to distinguish true peanut allergy from asymptomatic peanut sensitization in children referred for evaluation of suspected PA. In this cross-sectional study, 80 children aged 1–18 years were assessed in a tertiary allergy center in Poland. Sixty-five children with peanut sensitization underwent detailed clinical history assessment, skin prick testing, measurement of serum specific IgE including component-resolved diagnostics, basophil activation testing, and oral food challenges where clinically indicated. Clinically confirmed peanut allergy was diagnosed in 42 sensitized children. In univariate analyses, several clinical and immunological factors were associated with PA, including atopic comorbidities, peanut component sensitization, and basophil activation. Multivariate analysis identified food-induced anaphylaxis and walnut sensitization as independent factors associated with PA. In addition, a penalized diagnostic prediction model was developed to support clinical risk stratification. A multivariable diagnostic prediction model integrating clinical history and laboratory parameters demonstrated good discriminative performance in internal validation (area under the ROC curve 0.83). In conclusion, peanut allergy in sensitized children is determined by a combination of clinical and immunological factors rather than a single biomarker. Integrative diagnostic models may support risk stratification and help optimize the use of oral food challenges in specialized clinical settings, although external validation is required before broader implementation. Full article

Background: Pistachio allergy is an increasingly recognized form of tree nut allergy and is strongly associated with cashew allergy due to pronounced molecular cross-reactivity. Despite its relatively low prevalence in the general population, pistachio allergy may result in severe systemic reactions and represents a significant diagnostic challenge, particularly in polysensitized patients. Objective: This narrative review aims to critically evaluate current diagnostic approaches to pistachio allergy, with a focus on molecular allergen components, mechanisms of cross-reactivity, clinical phenotypes, and the added value of advanced diagnostic tools for risk stratification. Methods: A narrative synthesis of the literature was conducted, integrating data from population-based studies, clinical cohorts, component-resolved diagnostics, basophil activation testing, and oral food challenge studies. Emphasis was placed on the diagnostic performance and clinical utility of extract-based versus molecular and functional assays. Results: Pistachio allergy is predominantly associated with sensitization to seed storage proteins, including 2S albumins, 7S vicilins, and 11S legumins, which share high sequence and structural homology with corresponding cashew allergens. This molecular relationship underlies frequent co-sensitization and clinical co-reactivity. Conventional extract-based tests show limited specificity, whereas component-resolved diagnostics and functional assays improve diagnostic precision, facilitate phenotype-based risk stratification, and may reduce the need for oral food challenges in selected patients. Conclusions: Accurate diagnosis of pistachio allergy requires an integrated approach combining clinical history with molecular and functional diagnostics. Incorporation of component-resolved diagnostics and basophil activation testing into diagnostic algorithms allows improved differentiation between asymptomatic sensitization and clinically relevant allergy, supporting individualized patient management and safer clinical decision-making. Full article

Diagnosing wheat allergy remains challenging due to the use of oral wheat provocations, which implicate risks to patients and highlights the need for safer, non-invasive diagnostic methods. Here, we present the first direct comparison of a pediatric and adult cohort to study wheat allergy and wheat tolerance using an improved and validated basophil activation test (BAT). Blood samples from 24 children and 26 adults, clinically classified as facing oral food challenges, were analyzed using our bin-based BAT, enabling standardized data analysis and visualization. In children, the BAT showed significantly higher median basophil activation in wheat-allergic compared to wheat-tolerant individuals. Receiver operating characteristic analysis revealed that BAT responses to wheat, gluten, and gliadin extracts (area under the curve (AUC): 0.71–0.73) had greater diagnostic accuracies than extract-based wheat and gluten-specific immunoglobulin E (sIgE) measurements (AUC: 0.69, 0.70). However, Tri a 19-sIgE, showed the highest diagnostic performance (AUC: 0.97). In adults, BAT responses did not differ significantly between allergic and tolerant individuals. The bin-based BAT is a robust and reproducible diagnostic tool for wheat allergy diagnosis with automated data analysis capabilities. Significant differences were only evident in the pediatric cohort, indicating age-related immunological differences in basophil responsiveness or immune sensitization profiles. These differences could be linked to immune system maturation, variations in immunoglobulin E (IgE) avidity, or differential expression of the high-affinity IgE receptor (FcεRI) on basophils. While Tri a 19 sIgE was the best single predictor in children, its clinical utility remains controversial due to conflicting results in the scientific literature. Full article

This study presents the first documented case of a disease syndrome in cultured largefin longbarbel catfish (Hemibagrus macropterus). The condition is characterized by massive abdominal pseudotumor formation, severe cachexia, and functional gonadal arrest. Comprehensive pathological investigation revealed that the pseudotumor was encapsulated by fibroblasts and primarily composed of host-derived, poorly differentiated hyperplastic cells, interspersed with invasive, basophilic Type III cells. These cells and associated inflammatory–fibrotic lesions were also disseminated in the gill, kidney and spleen. Systematic diagnostic approaches, including microbiology and transmission electron microscopy, found no evidence of conventional bacterial or viral pathogens. Metagenomic analysis further supported these findings and suggested a link to infection by an as-yet-unidentified eukaryotic parasite, with Microsporidia or Ichthyosporea being the primary candidates. Functional (KEGG) profiling of the pseudotumor tissue further revealed a molecular signature consistent with active cellular proliferation and metabolism. We propose that the pseudotumor acts as a metabolically active “nutrient sink,” driving the systemic catabolism that underlies the severe cachexia and reproductive arrest. This work provides the first case of a eukaryotic parasite-induced pseudotumorous syndrome in fish, which represents an emerging threat to conservation aquaculture and offering novel insights into parasite-mediated host metabolic hijacking and tumor-mimicry. Full article

Food allergy diagnosis remains challenging due to the difficulty of distinguishing true clinical allergy from asymptomatic sensitization. Inaccurate diagnosis may result in unnecessary dietary restrictions, reduced quality of life, or, conversely, failure to identify individuals at risk of severe allergic reactions. This review critically analyzes the efficacy, limitations, and clinical utility of currently available diagnostic tests for food allergy, with particular emphasis on their ability to predict true clinical reactivity. A comprehensive literature review was conducted to evaluate the sensitivity, specificity, and predictive values of both traditional and emerging diagnostic modalities. English-language guidelines, systematic reviews, and key clinical studies published primarily within the past 15 years (up to 2025) were identified through PubMed and Google Scholar. Classic diagnostic tools, including skin prick testing (SPT) and serum-specific IgE (sIgE), were assessed alongside novel approaches such as component-resolved diagnostics (CRD), basophil activation test (BAT), mast cell activation test (MAT), atopy patch testing (APT), cytokine profiling, and omics-based diagnostics. Particular attention was given to how these tests compare with the oral food challenge (OFC), which remains the diagnostic gold standard. The findings demonstrate that while conventional tests offer high sensitivity and are valuable for initial risk assessment, their limited specificity often leads to overdiagnosis. Emerging molecular and cellular assays show improved specificity and functional relevance, especially in complex cases involving polysensitization or unclear clinical histories and may reduce reliance on OFCs in the future. However, accessibility, cost, and lack of standardization currently limit their widespread clinical application. Advances in artificial intelligence and data integration hold promise for improving diagnostic accuracy through enhanced interpretation of complex immunological data. Based on the synthesized evidence, this review proposes an evidence-based, stepwise, and individualized diagnostic algorithm for food allergy. Integrating clinical history, targeted testing, and selective use of OFCs can improve diagnostic certainty, enhance food safety, minimize unnecessary dietary avoidance, and optimize patient outcomes. The review underscores the need for continued research, standardization, and validation of novel diagnostic tools to support personalized and precise food allergy management. Full article

Background/Objectives: Patients with eosinophilic chronic obstructive pulmonary disease (COPD) often remain symptomatic despite optimized triple inhaled therapy. Dupilumab is a fully human monoclonal antibody that blocks the IL-4 receptor alpha subunit, thereby inhibiting IL-4 and IL-13 signaling. Evidence from randomized trials supports dupilumab for add-on treatment of type 2-high COPD, but data referring to short-term effectiveness in clinical practice are quite limited. Methods: We conducted an observational, compassionate-use study enrolling 13 consecutive outpatients with eosinophilic COPD (blood eosinophils ≥ 300 cells/µL) receiving add-on biologic therapy with dupilumab 300 mg every two weeks. Clinical (CAT, mMRC), functional (spirometry and body plethysmography), and inflammatory parameters (blood eosinophils/basophils, fibrinogen, FeNO) were evaluated at baseline and after four weeks of treatment. Safety was monitored after injection in a clinical setting, as well as via weekly phone follow-up. Results: Participants (84.6% male; mean age 67.08 ± 11.42 years) experienced rapid and clinically meaningful improvements at four weeks. CAT score decreased from baseline 21.40 ± 6.22 to 14.00 ± 5.58 (p < 0.001) and mMRC scale from 2.90 ± 0.73 to 1.80 ± 0.63 (p < 0.0001), respectively. Pre-bronchodilator FEV₁ increased from baseline 1.35 ± 0.65 L to 1.59 ± 0.84 L (p < 0.05), and FVC from 2.36 ± 0.92 L to 2.83 ± 1.11 L (p < 0.01). A marked lung deflation was observed: indeed, residual volume declined from baseline 4.17 ± 1.98 L to 3.47 ± 2.07 L (p < 0.05), with a concomitant reduction in specific effective airway resistance (from baseline 3.15 ± 1.77 to 2.43 ± 1.44 kPa·s; p < 0.05) associated with significant increases in mid-expiratory flow (FEF₂₅₋₇₅: from baseline 0.62 ± 0.38 to 0.86 ± 0.71 L/s; p < 0.05) and peak expiratory flow (3.80 ± 1.40 to 4.48 ± 1.79 L/s; p < 0.01). Type 2 inflammatory biomarkers changed as follows: blood eosinophil count fell from baseline 390.0 ± 43.75 to 190.0 ± 65.47 cells/µL (p < 0.001); blood basophil number decreased from baseline 37.50 ± 13.89 to 26.25 ± 13.02 cells/µL (p < 0.001); plasma fibrinogen lowered from baseline 388.4 ± 54.81 to 334.9 ± 72.36 mg/dL (p < 0.01); FeNO levels dropped from baseline 23.95 ± 18.10 to 14.00 ± 2.04 ppb (p < 0.0001). Dupilumab was well tolerated, and no treatment-related serious adverse events or discontinuations were detected. Conclusions: Within an exploratory context of daily medical activity referring to eosinophilic COPD already treated with maximal inhaled therapy, we found relevant therapeutic effects of a four-week add-on treatment with dupilumab. In particular, our patients manifested rapid improvements in symptoms, airflow limitation, and lung hyperinflation, paralleled by significant decrements of type 2 inflammatory signatures. Such encouraging results were associated with a favorable short-term safety profile. However, larger and longer studies are necessary to corroborate these preliminary findings. Full article

Myeloproliferative neoplasms (MPNs) are a heterogeneous group of diseases originating from hematopoietic stem cell transformation, characterized by the clonal proliferation of hematopoietic progenitors. A specific subset includes myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase (TK) gene fusions, particularly involving PDGFR A or B, which are sensitive to TK inhibitor treatment. We report a case of a 21-year-old patient with a myeloproliferative/myelodysplastic neoplasm, presenting with hyperleukocytosis, anemia, thrombocytopenia, and elevated LDH. The peripheral blood smear showed hypogranular neutrophils, eosinophils, basophils, and myeloid precursors. The absence of BCR::ABL1 and mutations in JAK2, CALR, and MPL excluded common MPNs. Cytogenetic analysis revealed a rearrangement between chromosomes 5 and 14. FISH analysis confirmed an inverted insertion from chromosome 5 to chromosome 14, involving the PDGFRB gene. WGS and RNAseq identified a fusion between PDGFRB and CCDC88C, causing the constitutive activation of PDGFRB. The fusion gene was confirmed by sequencing. This allowed for targeted therapy with a tyrosine kinase inhibitor (TKI), leading to molecular remission monitored by RT-qPCR. This case highlights how a multidisciplinary approach can identify atypical transcripts in MPN, guiding targeted therapy with TK inhibitors, thus resulting in effective treatment and molecular remission. Full article

Background: Diagnosing peanut allergy (PA) in children without known exposure remains challenging due to the need to distinguish true clinical allergy from asymptomatic sensitization. This study aimed to evaluate the diagnostic performance of individual and combined in vitro markers, particularly sIgE to Ara h 2, and to develop a multistage decision pathway that may reduce reliance on oral food challenge (OFC). Methods: Eighty children with suspected peanut allergy were prospectively enrolled. All participants, including healthy controls, underwent skin prick testing (SPT), measurement of sIgE to peanut and Ara h 2, and basophil activation testing (BAT). A multistage diagnostic algorithm incorporating these markers was constructed, and its performance was assessed using ROC analysis, predictive values, and likelihood ratios. A secondary analysis evaluated a simplified decision pathway excluding BAT. Results: sIgE to Ara h 2 demonstrated excellent individual performance (AUC 0.889), with 96.6% PPV at the optimal cut-off. The full multistage decision pathway (SPT + sIgE + BAT when interpretable) achieved 100% specificity and avoided OFC in 28.6% of children. However, BAT feasibility was limited; over 25% of results were uninterpretable. The simplified decision pathway (SPT + sIgE to Ara h 2) preserved 100% specificity and enabled the avoidance of OFC in 27.5% of cases, with slightly lower sensitivity. Conclusions: A structured in vitro diagnostic approach using sIgE to Ara h 2 and SPT can reliably identify peanut allergy in selected pediatric patients, particularly those without a reliable peanut exposure history. BAT enhances specificity but should be considered a confirmatory tool due to feasibility limitations. Full article

Transient receptor potential vanilloid 2 (TRPV2) is a non-selective cation channel involved in diverse physiological and pathological processes. Tranilast has frequently been described and used as a rather specific inhibitor of TRPV2. However, the molecular basis of this inhibition was never been studied in detail. Here, we investigated whether tranilast indeed directly inhibits TRPV2. Rat TRPV2 was expressed in human embryonic kidney (HEK293) cells, and channel function was assessed using whole-cell electrophysiology and calcium imaging in response to established agonists. In parallel, we conducted phagocytosis assays in rat basophilic leukemia (RBL) cells, including a CRISPR/Cas9-generated TRPV2-knockout cell line. Tranilast up to 1 mM did not inhibit TRPV2-mediated currents or calcium influx induced by any agonist. However, when co-applied with the oxidant chloramine T, tranilast diminished oxidation-induced activation of TRPV2. This effect may indicate a general interference of tranilast with redox signaling. Accordingly, tranilast also reduced chloramine T-induced activation of TRPA1 as well as the development of non-inactivating currents of voltage-gated Na⁺ channels. Furthermore, tranilast decreased phagocytic activity in both wildtype and TRPV2-knockout RBL cells. However, the reduction was less pronounced in TRPV2-knockout cells. These findings demonstrate that tranilast does not directly inhibit TRPV2. Instead, tranilast seems to indirectly suppress channel activation by reducing reactive oxygen species (ROS). This refined understanding of how tranilast modulates TRPV2 has important implications for the interpretation of prior and future pharmacological studies targeting TRPV2. Full article