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Background: Recognition of specific allergens triggering immune response is key for the appropriate prescription of allergen‐specific immunotherapy (SIT). This study aimed at evaluating the impact of using the commercially available microarray ImmunoCAPTM ISAC 112 (Thermo Fisher Scientific) on the etiological diagnosis and SIT prescription compared to the conventional diagnostic methods in patients with allergic rhinitis/rhinoconjunctivitis and/or asthma. Methods: 300 patients with respiratory allergic disease, sensitized to three or more pollen aeroallergens from different species, as assessed by a skin prick test (SPT) and specific IgE assays (sIgE), were included in this multicentric, prospective observational study. SPT and a blood test were performed to all patients. Total serum IgE and sIgE (ImmunoCAPTM) for allergens found positive in the SPT and sIgE allergen components (ImmunoCAPTM ISAC 112) were measured. Results: According to SPT results, the most prevalent pollen sensitizers in our population were Olea europaea followed by grass, Platanus acerifolia and Parietaria judaica. The molecular diagnosis (MD) revealed Ole e 1 as the most prevalent pollen sensitizer, followed by Cup a 1, Phl p 1, Cyn d 1, Par j 2, Pla a 1, 2, and 3 and Phl p 5. Immunotherapy prescription changed, due to MD testing, in 51% of the cases, with an increase of prescription of SIT from 39% to 65%. Conclusion: The identification of the allergen eliciting the respiratory disease is essential for a correct immunotherapy prescription. The advances in allergen characterization using methods, such as the commercial microarray ImmunoCAPTM ISAC 112, can help clinicians to improve SIT prescription. [ABSTRACT FROM AUTHOR]

Background: Studies on the prevalence of atopic dermatitis (AD) in adults in general populations are scarce worldwide. We performed a retrospective population-based observational cohort study of 537 098 adult patients diagnosed with AD in Catalonia, Spain, a larger population than in previous studies. Objectives: To study the prevalence of AD by age, sex, disease severity, multimorbidity, serum total immunoglobin E (tIgE), and appropriate medical treatment (AMT) for the population of Catalonia., Methods: The study population comprised adult individuals (≥18 years) diagnosed with AD according to medical records at different health care levels (primary, hospital, emergency) in the Catalan Health System. Statistical analyses were conducted to evaluate sociodemographic characteristics, prevalence, multimorbidity, serum tIgE, and AMT., Results: The prevalence of AD in the adult Catalan population was 8.7%, being higher for nonsevere disease (8.5%) than for severe disease (0.2%) and in females (10.1%) than in males (7.3%). Topical corticosteroids were the most prescribed drug (66.5%), and treatment was prescribed more frequently in severe AD patients, especially systemic corticosteroids (63.8%) and immunosuppressants (60.7%). More than half of severe AD patients (52.2%) had serum tIgE ≥100 kU/L, and higher values were observed for those with multimorbidity. The most frequent comorbid respiratory diseases were acute bronchitis (13.7%), allergic rhinitis (12.1%), and asthma (8.6%)., Conclusions: We provide new and robust evidence of the prevalence of AD and related characteristics in adults using a large-scale population-based study and a more significant cohort of individuals.

Introduction: This study compares the direct healthcare costs associated with asthma and chronic rhinosinusitis with nasal polyps (CRSwNP) from 2013 to 2017 in Catalonia (Spain) with a population control group without these conditions., Methods: A population administrative database containing healthcare information was used. The database contained information on primary care, hospitalisations, and emergency care from 2013 to 2017 in Catalonia. The unit cost of each healthcare procedure was imputed using a complete list of public prices for primary care services, hospital, and speciality services. Differential costs were estimated using a finite mixture model., Results: Individuals diagnosed with asthma or CRSwNP showed a higher incidence of comorbidities than the control group. Mean annual direct costs per patient were €1,102 for asthma, €1,612 for CRSwNP and €2,197 for those with both conditions. According to our estimations, differential costs were €162 - €274 for patients with asthma and €481 - €1,257 for patients with CRSwNP compared to the reference population. These costs were significantly higher when asthma and CRSwNP coexist and especially in their severe condition., Conclusion: This population-based study revealed that asthma and CRSwN are associated with great economic burdens for healthcare systems. These costs were significantly higher when comorbidity was present (asthma and CRSwNP) and especially in their severe condition (€4,441).

Background: Molecular diagnosis in allergology helps to identify multiple allergenic molecules simultaneously. The use of purified and/or recombinant allergens increases the accuracy of individual sensitization profiles in allergic patients., Objective: To assess the impact of molecular diagnosis through the ImmunoCAP TM ISAC 112 microarray on etiological diagnosis and specific immunotherapy (SIT) prescription. This was compared to the use of conventional diagnoses in pediatric, adolescent, and young adult patients with rhinitis or rhinoconjunctivitis and/or allergic asthma, sensitized to three or more pollen allergens of different botanical species., Methods: A multicenter, prospective, observational study was conducted in patients aged 3-25 years who received care at the Allergology service of 14 hospitals in Catalonia from 2017 to 2020. Allergology diagnosis was established based on the patient's clinical assessment and the results of the skin prick test and specific immunoglobulin E assays. Subsequently, molecular diagnosis was conducted using ImmunoCAP TM ISAC ® 112 to recombinant and/or purified allergen components., Results: A total of 109 patients were included; 35 (32.1%) were pediatric patients and 74 (67.9%) were adolescents or young adults (mean age: 18 years), with 58.0% being females. A change of 51.0% was observed in SIT prescription following molecular etiological diagnosis by means of a multi-parameter microarray., Conclusions: Molecular diagnosis by means of multi-parameter tests increases the accuracy of etiological diagnosis and helps to define an accurate composition of SIT., Competing Interests: M.L-H report research funding from Thermofisher. None of the other authors have anything to disclose.

Background: Type 2 inflammation has been described as a pathophysiological basis common to some diseases, such as atopic dermatitis (AD), chronic rhinosinusitis with nasal polyps, and asthma (CRSwNP)., Objective: The present study used population-based prevalence in Catalonia to analyse the coexistence of type 2 inflammatory diseases in patients primarily diagnosed with the above mentioned conditions., Results: We found a high degree of coexistence of type 2 inflammatory diseases among these patients, with the prevalence being higher in the severe forms, except for AD. For the severe forms of primary diseases, the proportion of patients with coexisting type 2 inflammatory diseases (severe or non-severe) was 16.2% for AD, 19.8% for asthma, and a striking 62.4% for CRSwNP. This patient population has the highest proportion of coexisting type 2 inflammatory diseases, both severe (48.9%) and non-severe (13.5%)., Conclusion: Our findings have significant implications for the management of patients with AD, asthma, and CRSwNP., (© 2024 The Author(s). Clinical and Translational Allergy published by John Wiley & Sons Ltd on behalf of European Academy of Allergy and Clinical Immunology.)

Immediate drug hypersensitivity reactions (IDHRs) are a burden for patients and the health systems. This problem increases when taking into account that only a small proportion of patients initially labelled as allergic are finally confirmed after an allergological workup. The diverse nature of drugs involved will imply different interactions with the immunological system. Therefore, IDHRs can be produced by a wide array of mechanisms mediated by the drug interaction with specific antibodies or directly on effector target cells. These heterogeneous mechanisms imply an enhanced complexity for an accurate diagnosis and the identification of the phenotype and endotype at early stages of the reaction is of vital importance. Currently, several endophenotypic categories (type I IgE/non-IgE, cytokine release, Mast-related G-protein coupled receptor X2 (MRGPRX2) or Cyclooxygenase-1 (COX-1) inhibition and their associated biomarkers have been proposed. A precise knowledge of endotypes will permit to discriminate patients within the same phenotype, which is crucial in order to personalise diagnosis, future treatment and prevention to improve the patient's quality of life., (© 2023 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: The Platelet-Activating Factor (PAF)/receptor (PAFR) system is involved in asthma and allergic rhinitis; however, its role in chronic rhinosinusitis (CRS) is still unclear. This study aimed to assess the expression of PAFR and the concentration of Lyso-PAF isoforms in the nasal polyps (NP) of patients suffering from CRS with/without comorbidities such as asthma and NSAID-exacerbated respiratory disease (N-ERD) compared to healthy nasal mucosa (NM) from control subjects., Methods: NM ( n = 8) and NP tissues were obtained from patients undergoing surgery for septal deviation/turbinate hypertrophy or endoscopic sinus surgery, respectively. Three phenotypes were studied: CRSwNP with no asthma ( n = 6), CRSwNP with non-steroidal anti-inflammatory drug (NSAID)-tolerant asthma ( n = 6), and CRSwNP with NSAID-exacerbated respiratory disease ( n = 6). PAFR protein and mRNA were assessed via immunochemistry, immunofluorescence, Western blot, and real-time quantitative PCR. Lyso-PAF isoforms (C16, C18, and C18:1) were quantified via mass spectrometry., Results: PAFR protein was expressed in the NM and NP, concretely in epithelial cells and submucosal glands. Compared to NM, PAFR mRNA expression was higher in all NP phenotypes ( p < 0.05) while all Lyso-PAF isoform concentrations were higher in the NP from asthmatic patients ( p < 0.05). Lyso-PAF C16 and C18 concentrations were higher in the NP from asthmatic patients than in the NP from patients without asthma., Conclusions: The PAF/PAFR system could play a pathophysiological role in CRSwNP pathogenesis.

Background: Studies on the prevalence of atopic dermatitis (AD) for the adolescent cohort in general-based large populations are scarce worldwide. We performed a retrospective population--based observational cohort study of 76,665 adolescent patients diagnosed with AD in Catalonia (Spain). We studied the prevalence of AD by age, gender, disease severity, comorbidities, serum total immunoglobulin E (tIgE) and appropriate medical treatment (AMT) for the Catalan population., Methods: Adolescent individuals (12-17 years) diagnosed with AD by medical records at different health care levels (primary, hospital, emergency) from the Catalan Health System (CHS) were included. Statistical analyses evaluated sociodemographic characteristics, prevalence, comorbidities, serum tIgE and AMT., Results: The overall diagnosed AD prevalence in the adolescent Catalan population (76,665) was 16.9%, being higher for the non-severe (16.7%) than for the severe (0.2%) populations. Topical corticosteroids were the most prescribed drug (49.5%), and the use of all prescribed treatments was higher in severe AD patients, especially systemic corticosteroids (49.7%) and immunosuppressants (45.4%). AD patients had, on average, a serum tIgE of 163.6 KU/L, which was higher for severe than non-severe disease (155.5 KU/L vs 101.9 KU/L, respectively). Allergic rhinitis (15.0%) and asthma (13.5%) were among the most frequent comorbid respiratory and allergy diseases., Conclusions: This is the first Spanish study reporting the overall diagnosed prevalence for a large-scale adolescent cohort (12-17 years old) from Catalonia. It provides new and robust evidence of AD's prevalence and related characteristics in this region., Competing Interests: All the authors received specific funding for developing this work from the International University of Catalonia (UIC) Real-World Evidence Chair. There are no patents, products in development or marketed products to declare. The authors of this manuscript have no relevant financial or other relationships to disclose.

MRGPRX2, a G-protein-coupled-seven transmembrane domain receptor, is mainly expressed in mast cells and neurons and is involved in skin immunity and pain. It is implicated in the pathophysiology of non-IgE-mediated immediate hypersensitivity and has been related to adverse drug reactions. Moreover, a role has been proposed in asthma, atopic dermatitis, contact dermatitis, and chronic spontaneous urticaria. Although it has a prominent role in disease, its signaling transduction is poorly understood. This study shows that MRGPRX2 activation with substance P increased Lysyl t-RNA synthetase (LysRS) translocation to the nucleus. LysRS is a moonlighting protein with a dual role in protein translation and IgE signaling in mast cells. Upon allergen- IgE-FcεRI crosslinking, LysRS is translocated to the nucleus and activates microphthalmia-associated transcription factor (MITF) activity. In this study, we found that MRGPRX2 triggering led to MITF phosphorylation and increased MITF activity. Therefore, overexpression of LysRS increased MITF activity after MRGPRX2 activation. MITF silencing reduced MRGPRX2-dependent calcium influx and mast cell degranulation. Furthermore, a MITF pathway inhibitor, ML329, impaired MITF expression, calcium influx, and mast cell degranulation. Moreover, drugs such as atracurium, vancomycin, and morphine, reported to induce MRGPRX2-dependent degranulation, increased MITF activity. Altogether, our data show that MRGPRX2 signaling enhances MITF activity, and its abrogation by silencing or inhibition resulted in defective MRGPRX2 degranulation. We conclude that MRGPRX2 signaling involves the LysRS and MITF pathway. Thus, MITF and MITF-dependent targets may be considered therapeutic approaches to treat pathologies where MRGPRX2 is implicated., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Guo, Ollé, Proaño-Pérez, Aparicio, Guerrero, Muñoz-Cano and Martín.)

Activating mutations in KIT (CD117) have been associated with several diseases, including gastrointestinal stromal tumors and mastocytosis. Rapidly progressing pathologies or drug resistance highlight the need for alternative treatment strategies. Previously, we reported that the adaptor molecule SH3 binding protein 2 (SH3BP2 or 3BP2) regulates KIT expression at the transcriptional level and microphthalmia-associated transcription factor (MITF) expression at the post-transcriptional level in human mast cells and gastrointestinal stromal tumor (GIST) cell lines. Lately, we have found that the SH3BP2 pathway regulates MITF through miR-1246 and miR-5100 in GIST. In this study, miR-1246 and miR-5100 were validated by qPCR in the SH3BP2-silenced human mast cell leukemia cell line (HMC-1). MiRNA overexpression reduces MITF and MITF-dependent target expression in HMC-1. The same pattern was observed after MITF silencing. In addition, MITF inhibitor ML329 treatment reduces MITF expression and affects the viability and cell cycle progression in HMC-1. We also examine whether MITF downregulation affected IgE-dependent mast cell degranulation. MiRNA overexpression, MITF silencing, and ML329 treatment reduced IgE-dependent degranulation in LAD2- and CD34 + -derived mast cells. These findings suggest MITF may be a potential therapeutic target for allergic reactions and deregulated KIT mast-cell-mediated disorders.

The development of vaccines against SARS-CoV2 brought about several challenges, including the management of hypersensitivity reactions to these formulations. The search for underlying mechanisms involved in these adverse events initially focused on excipients which may trigger mast cell activation responses via non-IgE pathways: polyethylene glycol and trometamol. We sought to determine whether these components, in their pure form, were capable of stimulating mast cells directly. To test this hypothesis, we used an in vitro model for non-IgE-mediated activation that has previously shown degranulation responses induced via MRGPRX2 with known drug agonists of the receptor. Human LAD2 mast cells were incubated with different concentrations (1, 10, 50 mg/ml) of trometamol and of purified polyethylene glycol/Macrogol (molecular weights: 2,000, 3,350, 4,000, and 6,000). Mast cell degranulation was assessed using a beta-hexosaminidase read-out. Interestingly, degranulation responses for all reagents tested showed no significant differences from those obtained from the negative control (basal degranulation). Receptor-silencing assays were therefore not conducted. In summary, purified PEG and trometamol did not induce mast cell degranulation in this in vitro model for the study of non-IgE mechanisms of drug hypersensitivity, previously shown to be useful in the investigation of MRGPRX2 ligands. Studies using complete vaccine formulations, lipid conjugates, and receptor gene variants are needed to further clarify mechanisms of vaccine hypersensitivity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2022 Quan, Ollé, Sabaté-Brescó, Guo, Muñoz-Cano, Wagner, Gastaminza and Martín.)