Inmunotek (Spain)

Exposomic determinants substantially influence the variability of molecular IgE-mediated sensitization in allergic rhinitis and conjunctivitis across bioclimatic regions, underscoring their relevance in precision allergology. This study aimed to characterize molecular sensitization profiles in Spanish patients with respiratory allergy from distinct geographic and climatic areas. A cross-sectional, multicenter study was performed in 12 Spanish cities. The study population comprised 291 patients diagnosed with allergic rhinitis and/or conjunctivitis according to the modified ARIA/DECA criteria. Participants underwent skin prick testing with standardized allergen extracts and multiplex molecular IgE analysis. Clinical, demographic, and regional bioclimatic variables were integrated to define exposomic sensitization patterns. Patients previously treated with allergen immunotherapy or biologics were excluded. Regional pooled sera were analyzed by ELISA and IgE immunoblotting to validate molecular data and identify IgE binding to nonrecombinant or poorly characterized allergenic components. Distinct regional sensitization profiles were identified. Grass pollen allergens predominated in oceanic and continental climates, while olive and cypress pollens were more frequent in Mediterranean areas. Sensitization to house dust mite, particularly Dermatophagoides pteronyssinus and Blomia tropicalis, was highly prevalent in subtropical and humid zones. Molecular assays confirmed skin test findings and identified major allergenic molecules, including Phl p 1, Ole e 1, Der p 1, and Der p 2, along with region-specific components such as Der p 23, Cup a 1, Alt a 1, and Pla a 2. This multicenter exposomic study demonstrated that climatic diversity modulates allergen sensitization in Spain, supporting region-tailored precision diagnostic and therapeutic strategies in respiratory allergy.

Background/Objectives: Allergen immunotherapy (AIT) with chemically modified allergoids represents a promising approach for the treatment of allergic rhinoconjunctivitis. This post hoc analysis investigated the clinical efficacy of a mannan-conjugated birch pollen allergoid (T502) by comparing outcomes in patients who received placebo in one pollen season and active treatment in the following year. Methods: Data were derived from four randomized clinical trials (EudraCT Numbers: 2018-002522-23, 2020-004126-32, 2021-002252-36, and 2022-004082-20) conducted over four consecutive years. Two independent patient groups were analyzed, with each group receiving placebo in the first year and subcutaneous T502 (10,000 mTU/mL) in the subsequent year. Daily symptom score (dSS), daily medication score (dMS), and combined symptom and medication score (CSMS) were assessed during the birch pollen season in April of each year. Results: In the first comparison between placebo in 2020 and an early treatment start in January 2021, treatment with T502 led to a 43.79% reduction in dSS (p ≤ 0.0001), a 71.43% reduction in dMS (p ≤ 0.001), and a 42.1% reduction in CSMS (p ≤ 0.001), all statistically significant. In the second comparison between placebo in 2022 and a late treatment start in March 2023, the reduction in dMS was 74.47% (p ≤ 0.001), whereas reductions in dSS (1.47%, p = 0.898) and CSMS (20.3%, p = 0.057) were not statistically significant. Conclusions: Subcutaneous immunotherapy (SCIT) with T502 significantly reduces allergic symptoms and medication use, particularly when all injections are completed before the onset of the birch pollen season in April. These findings highlight both the clinical value of T502 and the importance of optimized treatment timing.

BACKGROUND:Atherosclerosis is characterized by immune cell accumulation in the arterial wall and adaptive CD4+ T helper 1 immunity contributes to atherosclerosis development. However, how conventional dendritic cells (DCs) orchestrate this adaptive response remains controversial. This study unveils strategies for the gain and loss of function of cDCs to decipher their role in atherosclerosis induction in relation to adaptive T-cell immunity.METHODS:We tested atherosclerosis in Ldlr−/− mice fed a high-cholesterol diet (HCD). Expansion of DCs in vivo was achieved by overexpression of FLT3L (Fms-like tyrosine kinase 3 ligand), while the effect of ablation of conventional type 1 DCs (cDC1s) in atherosclerosis was analyzed by grafting bone marrow from different mouse models of cDC1 depletion, including Xcr1Cre−DTA and Irf8Δ32 mice, into lethally irradiated Ldlr−/− recipients before HCD. CD3+ T-cell subsets were analyzed using flow cytometry or single-cell RNA sequencing (scRNA-seq). Nanoparticles loaded with dexamethasone and decorated with anti-CLEC9A antibody to target cDC1s were tested for immunotherapy.RESULTS:Expansion of DCs in Ldlr−/− mice fed HCD for 8 weeks led to increased atherosclerotic lesion, which was prevented when Ldlr−/− mice were grafted before DC expansion with Xcr1Cre−DTA cDC1-depleted bone marrow compared with controls. Consistently, even in the absence of DC expansion, cDC1 deficiency prevented HCD-induced atherosclerosis. The scRNA-seq analysis of aortic CD3+ T cells in this experimental approach showed a local reduction in CD4+ Th1 and CD8+ IFN (interferon)-γ+ T cells in the absence of cDC1s compared with control mice. Mechanistically, stimulator of IFN genes (STING) in cDC1s was required for the proatherogenic function of cDC1s. As a potential cDC1-targeted immunotherapy for atherosclerosis, we generated lipid nanoparticles decorated with an anti-CLEC9A antibody to specifically target cDC1s. When loaded with the immunosuppressive drug dexamethasone, these nanoparticles promoted a reduction of the atherosclerotic lesion in Ldlr−/− mice fed HCD, correlating with decreased CD4+ Th1 and CD8+ IFN-γ+ T cells in the spleen. These immunosuppressive nanoparticles, however, did not impair antiviral response.CONCLUSIONS:Using state-of-the-art strategies, our results establish that cDC1s have a proatherogenic role in atherosclerosis by boosting CD4+ and CD8+ T-cell immunity and propose that cDC1s can be targeted with an immunosuppressive drug to decrease atherosclerosis progression.

The importance of the extracellular matrix (ECM) to pancreatic islets has been clearly demonstrated, as isolated islets grown in culture or transplanted, quickly lose viability and function after their matrix associations have been stripped away during the isolation process. Therefore, recapitulating the islet niche is a critical objective to move the field of islet transplantation forward. As a first step to recreating the islet microenvironment, we have recently developed a detergent-free decellularization method to obtain a decellularized solubilized ECM (dsECM) powder from human pancreas. We have also shown that this gentler method (compared to traditional detergent-based methods) allows for thorough preservation of the molecular fingerprint of the innate organ. Furthermore, incorporation of dsECM in alginate-microencapsulated human islets, showed a significant increase in insulin secretion, compared to both free and alginate-only encapsulated islets. However, it is also essential to test the interaction of dsECM with multiple cell types to establish its safety for transplantation. Herein, we present a comprehensive in vitro evaluation of the cytotoxicity, hemocompatibility and immunocompatibility of dsECM to establish a concentration range where it deemed safe and biocompatible. Furthermore, dsECM-based bioinks were coaxially bioprinted and the resulting construct's biocompatibility and vascularization potential were also evaluated in vivo.

The facilities where the experiments are carried out by our patient is called a pathogen-free area, which means that a series of requirements must be met, such as ventilated cages with microinsulators, closed buckets, negative pressure, constant exchange air, and specialized filters.Common tasks of our patient: Drug administration Taking samples, placing urinary catheter

Allergens from pollen, mites, and moulds often sensitise patients simultaneously, posing challenges for developing stable and effective combination vaccines. Alternaria alternata, a major source of indoor and outdoor allergens, is strongly linked to asthma development and contains proteolytic enzymes that can degrade other allergens, potentially reducing vaccine efficacy. This study aimed to evaluate the safety, efficacy, and stability of polymerised A. alternata extracts (allergoids) compared to native extracts and their compatibility with pollen extracts (Phleum pratense). Allergoids were prepared using glutaraldehyde and characterised through SDS-PAGE, LC-MS/MS, NMR, and gas chromatography. Their immunogenicity and IgE-binding properties were assessed via Western blot and ELISA competition assays, while enzymatic activity was analysed using ApiZym kits. Mice immunisation experiments were conducted to evaluate antibody responses. Polymerised extracts exhibited reduced IgE-binding capacity while maintaining IgG-binding and immunogenicity. Mice immunised with allergoids generated antibodies that efficiently blocked IgE binding in allergic patients. Proteolytic activity was significantly reduced in allergoids, and pollen extracts remained stable when combined with them. These findings demonstrate that A. alternata allergoids are a safer, more stable alternative for immunotherapy, offering enhanced efficacy and reduced injections for polysensitised patients. This study provides critical insights for designing optimised combination vaccines.

Climate change is significantly altering the dynamics of airborne allergens, affecting their seasonality, allergenicity, and geographic distribution, which correlates with increasing rates of allergic diseases. This study investigates aeroallergen sensitization among populations from Tenerife, Spain, and Lima, Peru-two regions with similar climates but distinct socio-economic conditions. Our findings reveal that Spanish individuals, particularly those with asthma, demonstrate higher sensitization levels to a broader range of allergens, especially mites, with 85% of participants reacting to at least one mite allergen. In contrast, Peruvian patients exhibit a narrower spectrum of sensitization. These results highlight the influence of environmental factors, such as pollution and socio-economic disparities, on allergen exposure and immune responses. Moreover, this study underscores the necessity for region-specific diagnostic and therapeutic strategies to effectively address these variations. By elucidating the intricate relationship between climate change, environmental factors, and allergen sensitization, this research offers insights into respiratory allergic conditions, advocating for tailored interventions to mitigate their impact across diverse populations.

BackgroundSubcutaneous immunotherapy has emerged as an effective option for treating allergic diseases. Here, we assessed the clinical impact of the mannan‐conjugated birch pollen polymerized allergoid T502 in birch pollen‐induced allergic rhinoconjunctivitis.MethodsIn this prospective, randomized, double‐blind placebo‐controlled phase III trial, 298 birch pollen–allergic adult patients were treated across 28 trial sites in Germany. Patients received either placebo or 23,000 mTU T502 subcutaneously over five pre‐seasonal visits. Efficacy was assessed by comparing the combined symptom and medication score (CSMS) between placebo and T502 during the peak birch pollen season 2022. Safety, tolerability and immunologic effects were also analyzed.ResultsDuring the peak birch pollen season, the median CSMS of the T502 group was reduced by 33% (p = 0.002) compared to placebo. The median daily symptom score and daily medication score were reduced by 30.4% (p < 0.001) and 56.3% (p = 0.045), respectively. Health related quality of life improved as reflected by reduction of RQLQ values by 31.5% (p < 0.0001). Production of Bet v 1 sIgG4 and Bet v 1 sIgG increased up to 6.2‐fold and 3‐fold respectively in the T502 group (p < 0.0001). The sIgE/sIgG4 ratio was strongly reduced in the T502 group at V7 (−62.9%, p < 0.0001).No fatalities nor serious adverse events were reported. In total, 16 systemic allergic reactions occurred (Grade I/II).ConclusionsTreatment with T502 significantly reduced symptoms and medication need in rhinoconjunctivitis patients. The treatment is well tolerated and safe.