Search Results (82)

Background/Objectives: Amb a 1 is the major allergenic component of Ambrosia artemisiifolia pollen and a clinically relevant marker of genuine ragweed sensitization. Heart failure is increasingly recognized as a systemic syndrome shaped by immune activation, endothelial dysfunction, fibrosis, neurohormonal imbalance, pulmonary comorbidity, and environmental exposures. This narrative review aims to synthesize the translational evidence linking Amb a 1-specific IgE, IgE-mediated inflammation, allergic airway disease, and cardiovascular remodeling in heart failure. Methods: A targeted narrative review was performed, integrating evidence on component-resolved ragweed diagnosis, IgE-FcεRI signaling, mast cell and eosinophil biology, pollen exposure, cardiovascular inflammation, and heart failure pathophysiology. Results: No dedicated clinical studies have validated Amb a 1-specific IgE as a diagnostic, prognostic, or therapeutic biomarker in heart failure. However, adjacent evidence supports biologically plausible links between allergen-specific IgE responses and cardiovascular dysfunction, including mast cell activation, cytokine release, endothelial perturbation, oxidative stress, microvascular dysfunction, pulmonary-cardiac interaction, and myocardial fibrosis. Amb a 1-specific IgE may therefore identify a seasonally vulnerable heart failure phenotype, particularly in patients with allergic rhinitis, asthma, eosinophilic inflammation, or recurrent symptom worsening during ragweed season. A systemic/indirect pathway operating through allergic airway disease is distinguished from a postulated direct cardiac pathway; the latter remains strictly speculative, as no direct evidence demonstrates that inhaled Amb a 1 reaches or activates cardiac mast cells in vivo. Conclusions: Amb a 1-specific IgE should not currently be used to infer cardiac causality or modify heart failure therapy. Prospective, phenotype-rich, exposure-informed studies are needed to determine whether ragweed sensitization has clinically meaningful implications for heart failure endotyping, seasonal risk assessment, and cardio-allergology care. These findings may inform patient-centered heart failure management by improving the interpretation of seasonal dyspnea, allergic comorbidity, and symptom fluctuations in ragweed-endemic regions. Full article

Background/Objectives: Rhinosinusitis (RS) is a prevalent inflammatory condition with substantial morbidity and variable response to standard therapies. Diet is a modifiable determinant of systemic inflammation, yet its role in sinonasal disease remains incompletely defined. Methods: A systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed, Scopus, Cochrane Library, and Web of Science were searched from inception through 28 June 2026. Studies assessing dietary exposures or interventions in RS were included using predefined criteria. Risk of bias was assessed using ROBINS-I and Joanna Briggs Institute tools. Due to heterogeneity in study design and outcomes, findings were synthesized narratively. Results: Ten studies met inclusion criteria (5 adult, 4 pediatric, 1 mixed), including interventional and observational designs. Anti-inflammatory dietary patterns were associated with improved sinonasal outcomes. In children, Mediterranean diet adherence reduced recurrent inflammatory episodes, and reduced sugar intake improved sinus infection scores with decreased TNF-α concentrations. In adults, both allergen-guided elimination diets and a low-arachidonic acid, low-salicylate, high-fiber dietary intervention improved symptom severity, with accompanying improvements in endoscopic outcomes. Observational studies demonstrated that higher fruit intake was associated with lower RS prevalence, whereas higher fat intake, caloric intake, Dietary Inflammatory Index scores, frequent meals prepared away from home, and ultra-processed food intake were associated with increased disease risk or sinonasal symptom burden. Phenotype-specific associations included increased dietary salicylate sensitivity and food-triggered symptom exacerbation among patients with nasal polyposis. Conclusions: Dietary patterns and specific nutritional exposures are associated with RS outcomes across age groups. Anti-inflammatory dietary profiles demonstrate potential protective effects, whereas pro-inflammatory dietary patterns are associated with increased disease burden. However, the predominance of observational data and study heterogeneity limit causal inference. Well-designed prospective and randomized studies are needed to define the therapeutic role of dietary modification in RS. Full article

Food allergy is an increasingly prevalent global health condition characterized by immune-mediated reactions to dietary antigens and a substantial clinical burden. Growing understanding of IgE-mediated mechanisms has highlighted the central role of type 2 inflammation, effector-cell activation, and impaired immune regulation. These advances have prompted the development of disease-modifying therapies beyond allergen avoidance. This narrative review summarizes recent advances in the therapeutic management of IgE-mediated food allergy. A structured PubMed search was performed to identify clinical trials, randomized studies, and meta-analyses published within the last five years. Both allergen-specific and non-allergen-specific interventions were evaluated. Current evidence supports oral immunotherapy as the most effective strategy for increasing reaction thresholds and inducing desensitization in peanut, milk, and egg allergies. However, safety concerns remain, and sustained unresponsiveness after treatment discontinuation is achieved inconsistently. Sublingual and epicutaneous immunotherapy show improved safety but lower efficacy. Modified allergen approaches, including baked milk and processed peanut products, may improve tolerability and facilitate immune modulation in selected patients. Biologic therapies, particularly anti-IgE agents, demonstrate efficacy both alone and when combined with immunotherapy. Emerging approaches include peptide vaccines, DNA immunization, microbiome-targeted interventions, and early dietary modulation. These strategies may improve durable immune tolerance through personalized, mechanism-based therapeutic approaches. Future progress will depend on optimizing safety, identifying predictive biomarkers, and integrating multimodal approaches to achieve durable immune tolerance. Full article

Background/Objectives: While ¹⁷⁷Lu-DOTATATE has demonstrated clinical efficacy in peptide receptor radionuclide therapy (PRRT) for neuroendocrine tumors (NETs), current dosing regimens do not account for potential sex-based pharmacokinetic differences. Our study systematically characterizes sex-dependent pharmacokinetic variations of ¹⁷⁷Lu-DOTATATE in preclinical models to provide the first preclinical evidence base informing future sex-stratified clinical investigations. Methods: Sex-stratified pharmacokinetic and biodistribution studies were conducted in male and female SD rats following intravenous administration of ¹⁷⁷Lu-DOTATATE at multiple dose levels: 2.86, 5.71, and 11.43 mCi/kg. Metabolic stability and renal excretion patterns were characterized. Safety assessments included acute toxicity, vascular irritation, hemolysis, and allergenicity testing. Therapeutic efficacy was evaluated exclusively in female AR42J xenograft-bearing CB-17 SCID mice. Results: Significant sex-dependent pharmacokinetic differences were observed at high (11.43 mCi/kg) and low (2.86 mCi/kg) dose levels, with females exhibiting 30–40% higher AUC and C_max values compared to males (p < 0.05). Both sexes demonstrated preferential accumulation in SSTR-expressing tissues, particularly the pancreas (females: 10.87 ± 2.51% ID/g; males: 9.10 ± 0.76% ID/g) and adrenal glands, with rapid clearance from non-target organs. Radio-HPLC analysis confirmed high metabolic stability with no detectable radiolabeled metabolites, and over 90% of radioactivity was recovered through renal excretion. Safety assessments demonstrated excellent tolerability across dose levels. In female xenograft models, treatment achieved tumor growth inhibition of 92.35–96.44% and 100% survival rate versus 10% in controls, though mid/high doses caused weight loss. Conclusions: Our study provides systematic preclinical evidence of sex-dependent pharmacokinetic differences in ¹⁷⁷Lu-DOTATATE, with females demonstrating significantly higher systemic exposure than males at specific dose levels. These findings establish the systematic preclinical evidence base for sex-dependent pharmacokinetic differences in ¹⁷⁷Lu-DOTATATE, providing a scientific rationale for incorporating sex as a stratification variable in future dosimetry-guided clinical studies. Full article

Background/Objectives: Topical treatment efficacy is fundamentally dependent on effective delivery of the active pharmaceutical ingredient and its compatibility with the compromised skin barrier. Many commercially available industrial formulations contain poorly tolerated excipients or lack essential therapeutic combinations, frequently leading to complex polypharmacy and reduced patient adherence. In contrast, magistral galenic preparations offer a degree of therapeutic personalization unmatched by standardized products, positioning the compounding laboratory as a strategic resource in dermatological care. This analysis aims to identify and evaluate ten indispensable magistral formulations selected based on their high clinical frequency and the absence of equivalent, globally available commercial alternatives. Materials and Methods: Each formulation was according to four strategic pillars: (i) dosage customization, (ii) excipient modification (removing allergens like parabens or fragrances), (iii) synergistic ingredient association, and (iv) vehicle optimization. The dermatological conditions addressed include pediatric scabies, melasma, hidradenitis suppurativa, and autoimmune mucosal diseases. Key selections include Kligman’s formula for hyperpigmentation and personalized trichological preparations. Results: The identified “top 10” magistral formulation reveals significant gaps within the standardized pharmaceutical market. In pediatric scabies (specifically patients < 15 kg), benzyl benzoate and precipitated sulfur demonstrate superior efficacy over permethrin, addressing emerging resistance patterns. For acute inflammatory dermatoses, Hoffmann Paste and Lime Liniment provide effective protective barriers while neutralizing local acidity. Antiseptic and astringent solutions, including Burow’s and Silver Nitrate (AgNO₃) offer targeted mechanisms and biocidal activity, often absent in standardized topicals. Furthermore, specialized adhesive oral pastes for autoimmune conditions minimizing systemic absorption and associated risks. Conclusions: Magistral compounding represents a cornerstone of precision medicine in dermatology enabling tailored therapies that bridge critical gaps left by standardized formulations, particularly in complex cases and vulnerable populations. Full article

Food allergies (FA) are a major public health concern in both children and adults. Immunoglobulin E (IgE)-mediated FA is characterized by allergic reactions driven by allergen-specific IgE and the subsequent degranulation of mast cells and basophils. Current FA management primarily involves avoidance of allergen-containing food, and more recently, therapies such as oral immunotherapy (OIT), sublingual immunotherapy (SLIT), and the anti-IgE biologic omalizumab. However, these interventions are not curative. The gut microbiome has been implicated in the development and regulation of oral tolerance to food antigens. This narrative review explores the role of probiotics, fecal microbiota transplantation (FMT), dietary interventions, and the interaction between the microbiome and OIT as potential strategies to manage established FA. We also explore barriers to their proliferation as part of regular clinical care. We conclude that future research should (1) address how the microbiome interacts with immunotherapies other than OIT, (2) explore the role of novel microbiome-based treatments like FMT as potential adjuvants to existing food allergy therapeutics, and (3) focus on developing standardized protocols and endpoints for microbiome-based therapeutics. Full article

Background/Objectives: Allergic asthma (AA) is a common chronic respiratory disease characterized by airway inflammation and bronchial hyperreactivity triggered by environmental allergens such as pollen and dust mites. Allergen-specific immunotherapy (AIT), particularly its sublingual formulation (SLIT), is the only treatment capable of modifying the disease’s natural course by targeting IgE-mediated sensitization mechanisms. Methods: We analyzed demographic, clinical, functional (FEV₁, FVC, FEV₁/FVC), and immunological data (specific IgE for Phl p1, Phl p5, Der p1, Der p2, Der p23), alongside asthma control parameters (ACT score), reliever use, and exacerbation frequency, in patients undergoing SLIT for grass pollen and dust mite allergens. Results: After at least twelve months of treatment, we observed significant reductions in exacerbation rate (p < 0.01) and reliever use (p = 0.0002). These improvements were particularly evident in the subgroup receiving grass pollen SLIT (p = 0.03 and p = 0.01, respectively). An increase in ACT score was observed but did not reach statistical significance (p = 0.07), likely due to already high baseline control. All patients reported improved rhinitis symptoms. Lung function parameters showed no significant changes. SLIT was well tolerated, with no serious adverse events or discontinuations. The subgroup of patients treated with dust mite SLIT was small, limiting the statistical power and generalizability of these findings. Consequently, the dust mite results should be interpreted cautiously and considered exploratory. The more robust and statistically supported findings pertain to the grass pollen SLIT group, reflecting a more consolidated evidence base for this allergen. Conclusions: SLIT for grass pollen demonstrated promising, statistically supported benefits in reducing exacerbations and improving disease control, supporting its role as an effective adjunct therapy in AA. While dust mite SLIT also showed positive trends, the limited sample size warrants further investigation to confirm these preliminary findings. Overall, SLIT appears to be a safe and potentially beneficial option for patients with AA and allergic rhinitis, but larger studies are needed to substantiate its efficacy across different allergens. Full article

Background and Objectives: The average prevalence of sensitization to house dust mite in developed countries is more than 20%. The three major allergens of D. pteronyssinus—Der p 1, Der p 2, and Der p 23—have been associated with asthma severity. Allergen-specific immunotherapy (ASIT) is the only personalized and effective treatment that can change the natural course of allergic diseases such as allergic rhinitis or allergic asthma. Despite ASIT being an established treatment method, its effectiveness is still assessed using patient-reported outcome measures that determine quality of life, and there are no objective biomarkers that can accurately and reliably indicate the therapeutic efficacy of ASIT. This study aimed to monitor sensitization profiles to allergens, assess the effectiveness of ASIT, and evaluate total nasal symptom score (TNSS) and quality of life after six months of ASIT treatment. Materials and Methods: The molecular allergy diagnostic system was used to assess changes in patients’ sensitization profiles to allergens, and the validated questionnaires RQLQ and TNSS were used for quality-of-life assessment. Results: After 6 months of ASIT treatment against house dust mite allergens, a statistically significant increase in sIgE against the Der p 23 component was noted. In addition, a significant decrease in practical problems and an improvement in patients‘ emotional state were observed, while the TNSS score remained unchanged. Conclusions: Continuous monitoring of the Der p 23 component during further stages of ASIT is, therefore, essential to determine whether the observed changes reflect de novo sensitization or represent an immunological response to therapy. Full article

Shellfish allergy is among the most common food allergies (FAs) worldwide and represents a severe immunoglobulin E (IgE)-mediated FA with tropomyosin functioning as the predominant pan-allergen. Current management of shellfish allergies is strictly palliative with allergen avoidance, underscoring the critical need for disease-modifying therapies. While conventional allergen-specific immunotherapy (AIT) approaches, namely oral and sublingual immunotherapies, demonstrate capacity for desensitization, more clinical applications are needed in the potential safety concerns and prolonged treatment durations. Innovative treatments, such as the design of modified shellfish allergens, DNA vaccine technologies, and nanoparticle-based delivery platforms such as virus-like particles (VLP), show efficacy and potential in inducing protective antibodies while promoting antigen-specific immune tolerance with reduced allergenic risks. These innovative approaches hint at a promising pathway in achieving safe, effective, and long-lasting clinical tolerance for shellfish allergy. This review describes the current perspectives on allergen immunotherapy regarding shellfish allergy and analyzes emerging therapeutic strategies poised to overcome these limitations. Full article

Food has a massive influence on the gut microbiota and is one of the most useful therapeutic levers in disease. Recent developments have highlighted how macronutrient balance, food format, and functional ingredients can regulate microbial diversity, metabolism, and host physiology in companion animals such as dogs and cats. This narrative review condenses evidence on the bidirectional gut microbiota–diet connection and on nutritional therapy for gastrointestinal, metabolic, renal, hepatic, and immune-mediated disorders. Protein-based diets including high or hydrolyzed protein, omega-3 acids, fermentative fiber, and probiotics can positively affect microbial composition, stimulate short-chain fatty acid synthesis, and enhance intestinal barrier functions. Conversely, excess fats or refined carbohydrates may cause dysbiosis, inflammation, and metabolic imbalances. Numerous studies have shown that therapeutic nutrition—e.g., low-protein renoprotective, hepatoprotective antioxidants, and allergen-elimination diets—holds enormous potential for treatment. In addition, fecal microbiota transplantation (FMT) can be used as an additive therapy for resistant gastrointestinal illnesses. Despite these developments, constraints remain in terms of standardization, study duration, and species-specific data, especially for cats. This review underscores dietary modification as a clinically actionable tool for microbiota-targeted therapy and calls for integrative, multi-omics research to translate microbiome modulation into precision nutrition for companion animals. Full article

Eosinophilic esophagitis (EoE) is a chronic, immune-mediated disorder characterized by eosinophilic infiltration of the esophageal epithelium, primarily driven by exposure to food and aeroallergens. Although dietary elimination remains the cornerstone of therapy, the identification of specific food triggers still largely relies on empiric methods. This narrative review explores the diagnostic and therapeutic role of component-resolved diagnostics (CRD) and other molecular tools in the personalized management of EoE. Across observational and cohort studies, CRD has shown improved sensitivity in detecting clinically relevant allergen sensitizations compared with conventional tests, allowing for more precise dietary guidance and, in some cases, reducing unnecessary food exclusions. However, remission rates achieved through CRD-guided diets remain comparable or slightly lower than those obtained with empiric elimination, highlighting the need for validation in prospective, controlled studies. Recent advances in omics-based diagnostics, including gene expression profiling and proteomic biomarkers, further underscore the potential of integrating molecular and immunologic endotyping into clinical practice. Overall, current evidence supports CRD as a promising adjunctive tool that enhances the precision of allergen identification but is not yet ready to replace empiric dietary strategies. Future research should focus on validating standardized CRD-guided algorithms, integrating omics-derived biomarkers, and developing non-invasive diagnostic platforms. Incorporating dietitian-led nutritional assessment and biomarker monitoring into CRD- and omics-informed care pathways may help prevent nutrient deficiencies, improve adherence, and translate molecular precision into safer, patient-centered dietary management. Full article

Background: Chronic hepatitis B (CHB) remains being a major public health threat, and currently existing CHB therapies have limited efficacy and side effects. We have recently developed a vaccine termed VVX001 based on a recombinant fusion protein consisting of the preS domain of the large surface protein of hepatitis B virus (HBV) fused to grass pollen allergen peptides. VVX001 has been shown to induce preS-specific antibodies in grass pollen allergic patients, and sera of immunized subjects inhibited HBV infection in vitro. Methods: In this study we investigated if immunization with VVX001 can induce preS-specific antibodies in CHB using the adeno-associated virus (AAV)-HBV murine model of CHB. Six groups of C57BL/6 female mice (n = 6) were transduced with AAV-HBV or AAV-Empty, and after six weeks, they were immunized five times with 20 µg of aluminum hydroxide-adsorbed VVX001 or preS or vehicle (Alum alone). Serum samples were taken continuously. Two weeks after the last immunization, spleen and liver mononuclear cells were collected. Serum reactivity to preS and preS-derived peptides was assessed by ELISA. B-cell responses were measured by ELISPOT assay, and intrahepatic lymphocyte (ILH) counts were determined by FACS. HBV DNA, HBsAg, HBeAg, ALT, and AST were assessed using commercial kits. Results: Our results show that VVX001 induces preS-specific IgG antibodies that cross-react with different HBV genotypes A-H and are directed against the sodium taurocholate co-transporting polypeptide (NTCP) receptor binding site of preS both in mice with and without HBV. Actively immunized AAV-HBV-treated mice had a higher number of intrahepatic lymphocytes than vehicle-vaccinated and mock-transduced animals. Conclusions: These findings encourage performing further trials to study the potential of VVX001 for therapeutic vaccination against CHB. Full article

IgG antibodies, signaling via the inhibitory receptor, FcγRIIb, are potent inhibitors of IgE-mediated mast cell activation. We have previously reported that in addition to blocking mast cell degranulation, inhibitory IgG signals shut down a proinflammatory transcriptional program in which mast cells produce cytokines and chemokines known to drive type 2 tissue inflammation. To determine whether such effects of allergen-specific IgG can modulate allergic inflammation in vivo, we examined the airways of mice sensitized to ovalbumin (OVA) by intraperitoneal injection and then challenged with intranasal OVA. Pretreatment with allergen-specific IgG significantly reduced the recruitment of inflammatory cells, including macrophages and eosinophils, into the lungs of OVA-sensitized mice. The bronchoalveolar lavage fluid of OVA-challenged mice contained elevated levels of chemokine ligands (CCL2 and CCL24) and interleukin-5, a response that was markedly blunted in animals receiving allergen-specific IgG. IgG-treated animals exhibited attenuated allergen-induced production of IgE, IL-4, and IL-13, along with impaired OVA-induced goblet cell hyperplasia and Muc5ac expression and suppressed airway hyperresponsiveness, consistent with a shift away from a Th2 response. Using mice with a lineage-specific deletion of FcγRIIb, we demonstrated that each of these protective effects of IgG was dependent upon the expression of this receptor on mast cells. Overall, our findings establish that allergen-specific IgG can reduce allergen-driven airway inflammation and airway hyperresponsiveness and point to a mechanistic basis for the therapeutic benefit of aeroallergen-specific IgG therapy. Full article

House dust mites (HDMs) are a major source of indoor allergens, significantly contributing to allergic rhinitis, asthma and atopic dermatitis. This review examines the epidemiology, microbiological classification and pathophysiology of HDM allergy, highlighting key allergens such as Der p 1, Der p 2 and Der p 23. Furthermore, we discuss the pivotal role of allergen-specific immunotherapy (AIT), the only disease-modifying treatment for immunoglobulin (Ig)-E disease. Recent studies have identified predictive biomarkers for allergen-specific immunotherapy (AIT) efficacy, including the specific IgE to total IgE (sIgE/tIgE) ratio and regulatory follicular T cell profiles, supporting a more personalized approach to therapy. Additionally, emerging immunotherapy strategies, such as recombinant allergens and peptide-based formulations, aim to improve safety and clinical outcomes. As HDM allergy prevalence rises globally, further research into optimizing diagnostics and treatment strategies remains crucial for enhancing patient care. Full article

Background/Objectives: Allergen immunotherapy is the sole therapeutic option capable of modifying the natural course of allergic rhinitis and preventing the development of asthma. Results from paediatric patients are scarce. To evaluate the effectiveness and safety of a glutaraldehyde-modified extract of mites (Beltavac^®) administered for one year under clinical routine conditions in children between 3 and 11 years old. Methods: This was a multicentre, prospective, 13-month cohort study. Among 97 children diagnosed with immunoglobulin E-mediated house dust mite allergic rhinoconjunctivitis, 87 initiated the subcutaneous immunotherapy. The main outcomes included the Combined Symptoms and Medication Score (CSMS), assessed for 1 month at baseline and after 1, 6, and 12 months, and the number of adverse reactions according to the WAO adverse reaction grading system. The levels of serum-specific immunoglobulins were also assessed. Results: CSMS improved scores throughout therapy (adjusted mean change and 95% confidence interval: 0.55, 0.26–0.84 points; p < 0.001). Improvements occurred in both children with (n = 68) and without asthma (n = 19), as well as in children aged ≥6 years (n = 76) and <6 years (n = 11), although statistical significance was not reached in the smallest subgroups. Eight children (9.2%) developed a total of 15 adverse reactions. Most occurred after the initial dose (five out of eight children), and were local (six out of eight) and minor (five out of eight). Over 90% of patients completed the full regimen. Conclusions: This study supports the effectiveness and safety of allergen immunotherapy administered according to a rush schedule for one year for paediatric allergic rhinitis. Full article