Coupling of a Major Allergen to the Surface of Immune Cells for Use in Prophylactic Cell Therapy for the Prevention of IgE-Mediated Allergy.

Mengrelis K, Niederacher G, Prickler L, Kainz V, Weijler AM, Rudolph E, Stanek V, Eckl-Dorna J, Baranyi U, Spittler A, Focke-Tejkl M, Bohle B, Valenta R, Becker CFW, Wekerle T, Linhart B.  Cells. 2024 Mar 3;13(5):446. doi: 10.3390/cells13050446.

Abstract

Biochemical analysis of recombinant and lipidated Phl p 5 allergens. A–C Analysis of Phl p 5 for EDC coupling. 

Up to a third of the world’s population suffers from allergies, yet the effectiveness of available preventative measures remains, at large, poor. Consequently, the development of successful prophylactic strategies for the induction of tolerance against allergens is crucial. In proof-of-concept studies, our laboratory has previously shown that the transfer of autologous hematopoietic stem cells (HSC) or autologous B cells expressing a major grass pollen allergen, Phl p 5, induces robust tolerance in mice. However, eventual clinical translation would require safe allergen expression without the need for retroviral transduction. Therefore, we aimed to chemically couple Phl p 5 to the surface of leukocytes and tested their ability to induce tolerance. Phl p 5 was coupled by two separate techniques, either by 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) or by linkage via a lipophilic anchor, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-poly(ethylene glycol)-maleimide (DSPE-PEG-Mal).

Mast cell activation disrupts interactions between endothelial cells and pericytes during early life allergic asthma

Joulia R, Puttur F, Stölting H, Traves WJ, Entwistle LJ, Voitovich A, Garcia Martín M, Al-Sahaf M, Bonner K, Scotney E, Molyneaux PL, Hewitt RJ, Walker SA, Yates L, Saglani S, Lloyd CM.  J Clin Invest. 2024 Mar 15;134(6):e173676. doi: 10.1172/JCI173676.

Abstract

Allergic asthma generally starts during early life and is linked to substantial tissue remodeling and lung dysfunction. Although angiogenesis is a feature of the disrupted airway, the impact of allergic asthma on the pulmonary microcirculation during early life is unknown. Here, using quantitative imaging in precision-cut lung slices (PCLSs), we report that exposure of neonatal mice to house dust mite (HDM) extract disrupts endothelial cell/pericyte interactions in adventitial areas.

Dexamethasone protects against asthma via regulating Hif-1α-glycolysis-lactate axis and protein lactylation

Chen N, Xie QM, Song SM, Guo SN, Fang Y, Fei GH, Wu HM.  Int Immunopharmacol. 2024 Mar 8;131:111791. doi: 10.1016/j.intimp.2024.111791. 

Abstract

Purpose

Asthma can not be eradicated till now and its control primarily relies on the application of corticosteroids. Recently, glycolytic reprogramming has been reportedly contributed to asthma, this study aimed to reveal whether the effect of corticosteroids on asthma control is related to their regulation of glycolysis and glycolysis-dependent protein lactylation.

Methods

Ovalbumin (OVA) aeroallergen was used to challenge mice and stimulate human macrophage cell line THP-1 following dexamethasone (DEX) treatment. Airway hyperresponsiveness, airway inflammation, the expressions of key glycolytic enzymes and pyroptosis markers, the level of lactic acid, real-time glycolysis and oxidative phosphorylation (OXPHOS), and protein lactylation were analyzed.

Results

DEX significantly attenuated OVA-induced eosinophilic airway inflammation, including airway hyperresponsiveness, leukocyte infiltration, goblet cell hyperplasia, Th2 cytokines production and pyroptosis markers expression. Meanwhile, OVA-induced Hif-1α-glycolysis axis was substantially downregulated by DEX, which resulted in low level of lactic acid. Besides, key glycolytic enzymes in the lungs of asthmatic mice were notably co-localized with F4/80-positive macrophages, indicating metabolic shift to glycolysis in lung macrophages during asthma.

Practical Use of Upadacitinib in Patients with Severe Atopic Dermatitis in a Real-World Setting: A Systematic Review

Luciano Ibba, Luigi Gargiulo, Carlo Alberto Vignoli, Giovanni Fiorillo, Mario Valenti, Antonio Costanzo & Alessandra Narcisi . Clinical, Cosmetic and Investigational Dermatology, 17:, 593-604, DOI: 10.2147/CCID.S329442 

Abstract

Upadacitinib is a selective Janus kinase inhibitor approved for the treatment of severe atopic dermatitis (AD). This systematic review aims to summarize the most recent data in terms of effectiveness and safety of upadacitinib in the treatment of severe AD in a real-world setting. The review included a comprehensive search of databases, including PubMed, Google Scholar and Web of Science, according to Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. The literature search initially identified 242 studies.

A prospective observational study correlating possible novel biomarkers with disease severity and antihistamine response in chronic spontaneous urticaria

Bhatia D, Mehta H, Bishnoi A, Srivastava N, Vinay K, Parsad D, Kumaran MS. Asia Pac Allergy. 2024 Mar;14(1):5-11. doi: 10.5415/apallergy.0000000000000132.

Abstract

Background:

Role of complement fraction 5a (C5a), interleukin (IL)-9, and apolipoprotein (apo) A-IV as biomarkers of disease severity and antihistamine response in chronic spontaneous urticaria (CSU) remains elusive.

Objective:

To identify the role of C5a, IL-9, and apo A-IV as potential biomarkers in predicting disease severity and antihistamine response in CSU patients.

Methods:

This was a prospective observational study of 95 patients and 42 controls. Serum analysis of C5a, IL-9, and apo A-IV was done using enyzme linked immunosorbent assay kits. Also, serum IgE and anti-thyroid peroxidase (TPO) levels were assessed in all patients. All patients were started on oral levocetirizine 5 mg at baseline and dose was titrated upwards to maximum of 20 mg based on response. Patients were categorized into antihistamine responders or nonresponders as per their disease response.

The autologous serum skin test (ASST) predicts the response to anti-IgE treatment in Chronic Spontaneous Urticaria patients: a prospective study

Palladino A, Villani F, Pinter E, Visentini M, Asero R. Eur Ann Allergy Clin Immunol. 2024 Mar 14. doi: 10.23822/EurAnnACI.1764-1489.337.

Abstract

Background. Chronic spontaneous urticaria (CSU), characterized by recurrent itchy wheals and angioedema for > 6 weeks, is a quite common disease that may heavily impair the quality of life. Omalizumab, an anti-IgE mAb, has much improved the management of CSU but patients' response to the drug may vary and predictive markers are still largely missing. We investigated the predictive value of the autologous serum skin test (ASST) on omalizumab response. 

Methods. 15 patients with severe CSU eligible for omalizumab treatment were prospectively studied submitting them to ASST and to complete blood count, D-dimer, anti-thyroid peroxidase antibodies, and total IgE measurement before the start of the treatment. 

Summary table of the differences between the means of the two
groups of patients divided according to the response to therapy.

Results. 14/15 (93%) responded brilliantly to omalizumab at 3 months assessment. 7 responded in less than 1 month ("early responders") and 7 only after multiple administrations ("late responders"). Of 9 patients scoring positive on ASST, 7 (78%) were late, and 2 (22%) early responders to omalizumab (p = 0.021).

Pharmacists’ Attitudes Towards Long-Term Use of Nasal Decongestants: A Cross-Sectional Study

Mokhatrish MM, Almatrafi SD, Aldrees TM, Aldriweesh TA, AlGhamdi FM, Al-Dosary AS, Alhumaydani NK, Aldakkan OZ, Alrudian N, Ali AH.  J Multidiscip Healthc. 2024;17:1079-1090
https://doi.org/10.2147/JMDH.S451835

Background: Rhinitis medicamentosa is a nonallergic inflammation of the nasal mucosa caused by topical decongestants overuse. It mainly affects young and middle-aged adults. Therefore, the aim of this study was to investigate the attitudes of pharmacists regarding the utilization of over-the-counter intranasal decongestants.

Methods: An online cross-sectional study was conducted from November 2021 to January 2022. The target population of the study included pharmacists who work in community pharmacies in Saudi Arabia. Binary logistic regression analysis was used to identify predictors of having positive attitude towards controlling the use of decongestant.

Most prevalent symptoms of patients asking for NDs.

Results: A total of 220 participants were included in this study. Around 15.0% of them reported that ND come with a physician prescription. The majority of the participants (87.3%) reported that the less than 5 days is the maximum safe duration for the use of NDs. Overall, the study participants demonstrated moderately positive attitude towards controlling the use of decongestant with a mean attitude score of 2.5 (standard deviation: 1.2) out of 5; which represents 50.0% of the maximum score.

Component-specific clusters for diagnosis and prediction of allergic airway diseases

Howard R, Fontanella S, Simpson A, Murray CS, Custovic A, Rattray M. Clin Exp Allergy. 2024; 00: 1-11. doi:10.1111/cea.14468

Abstract

Background

Previous studies which applied machine learning on multiplex component-resolved diagnostics arrays identified clusters of allergen components which are biologically plausible and reflect the sources of allergenic proteins and their structural homogeneity. Sensitization to different clusters is associated with different clinical outcomes.

Objective

To investigate whether within different allergen component sensitization clusters, the internal within-cluster sensitization structure, including the number of c-sIgE responses and their distinct patterns, alters the risk of clinical expression of symptoms.

Methods

In a previous analysis in a population-based birth cohort, by clustering component-specific (c-s)IgEs, we derived allergen component clusters from infancy to adolescence. In the current analysis, we defined each subject's within-cluster sensitization structure which captured the total number of c-sIgE responses in each cluster and intra-cluster sensitization patterns.