Allergy discordant twins do not exhibit differences in gene expression in non-switched and switched B cellsStephan Schneider1, Pattraporn Satitsuksanoa1, Huseyn Babayev2, Willem van de Veen1, Iris Chang3, Minglin Yang1, Cezmi A. Akdis1, Kari Nadeau4, Mübeccel Akdis11 Swiss Institute of Allergy and Asthma Research, University of Zurich, Davos, Switzerland2 Abant Izzet Baysal University Hospital, Department of Medical Microbiology, Bolu, Türkiye3 Department of Pediatrics/ Division of Hematology, Oncology, Stem Cell Transplantation, and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA4 Harvard TH Chan School of Public Health, Department of Environmental Health, Boston, Mass. USA 02115To the Editor,Allergy is a globally spread affliction that is based on dysregulation of immune responses towards ‘harmless’ antigens.1 B cells and their regulation are at the center of allergic disease mechanisms.2,3 They produce IgE, which is essential for allergen-induced mast cell and basophil degranulation.4 The common consensus is, that the regulation of B cells is closely tied to tolerance and allergy.2,5 In allergy this regulation is likely dysfunctional, resulting in different B cell behaviour. Therefore we performed whole transcriptome analysis on peripheral B cells from twins who were discordant or concordant for allergic diseases to identify allergy-associated differential gene expression patterns (i.e. receptors to a type 2 response). We sorted switched and non-switched B cells from 16 twin pairs that were either healthy, allergy discordant or allergy concordant and performed bulk RNA sequencing to identify differences in gene expression patterns. We hypothesized that there would be significantly different expressions in pathways related to B cell activation, B cell regulation or B cell isotype switching correlating to allergic symptoms. The donors were monozygotic and mainly allergic to timothy grass, birch tree pollen and/or house dust mites; none had taken or were on allergen-immunotherapy (Supplementary Table 1-3). Samples were obtained via ethics approval and consent. We sorted switched and unswitched B cells from bio-banked PBMCs, extracted RNA, depleting the ribosomal RNA, and performed 100bp single-end RNA sequencing on the Illumina Novaseq 6000 platform.6 Unbiased clustering, excluding long non-coding RNA, (Figure 1A) showed that the main influences for clustering in descending order are switched vs non-switched B cells, twin pairs and then their concordance status. An individuals allergy status had little to no significant impact on the overall clustering. The same holds true for the PCA analysis of the top 300 significant genes across all samples (Figure 1B). Comparing healthy concordant to allergy concordant twins could be greatly influenced by confounding factors like twin pair similarities and grouping by concordance instead of their actual healthy status. For these reasons, we compared the healthy vs allergic within the discordant twin pairs to avoid these influences for gene expression analysis. In this comparison, neither switched nor non-switched B cell show pathways that would traditionally be associated with allergies or B cell regulation in particular (Supplementary Table 4). A log fold change of greater than 0.5 and a p-value of 0.05 gave a FDR of 0.9999. Adjusting for a FDR below 0.05 (p-value <0.00001) resulted no differentially expressed genes for switched and 5 genes without a common pathway in non-switched B cells. Using this methodology of analysis, we did not find significant differences in pathway regulations on the wider scale of B cells between allergy-discordant twins.PCA analysis for the top 300 genes by the p-value of the allergy-discordant twins confirmed that allergic vs healthy twins do not group by allergy status (Figure 2A). Pathway analysis of the top genes in allergy-discordant twins does not reveal any cohesive pathways (allergy vs healthy) in the switched B cells (Figure 2B). There is one pathway in the upregulated genes of the non-switched B cells, whose genes are associated with the cell cycle and not directly with immune functions.Our results show no indication that there is a general dysregulation of B cells as an underlying cause for allergies. Any differences that might exist are too subtle to be observed across B cells. We propose that distinctions between allergic and non-allergic individuals may only be noticeable in allergen-specific B cells. These effects are probably overshadowed by the variability among individuals due to the rarity of allergen-specific B cells in the overall B cell population.

CLA + memory T cells constitute a small subset of human memory T cells. Circulating skin-homing T cells participate in several aspects of atopic dermatitis, such as Staphylococcus aureus involvement in inflammation, the abnormal Th2 immune response, biomarkers, clinical aspects of the patients, pruritus, and the mechanism of action of targeted therapies. Superantigens, IL-13, IL-31, pruritus, CCL17 and early effects on dupilumab-treated patients have in common that they are related to CLA + T cell response in patients. The function of CLA + T cells is closely related to the role of T cells belonging to the skin-associated lymphoid tissue and could be a reason why they reflect different mechanisms of atopic dermatitis. The goal of this review is to gather all this translational information of atopic dermatitis pathology.

There has been an important change in the clinical characteristics and immune profile of COVID-19 patients during the pandemic thanks to the extensive vaccination programs. Here, we highlight recent studies on COVID-19, from the clinical and immunological characteristics to the protective and risk factors for severity and mortality of COVID-19. The efficacy COVID-19 vaccines and potential allergic reactions after administration are also discussed. The occurrence of new variants of concerns such as Omicron BA.2, BA.4 and BA.5 and the global administration of COVID-19 vaccines have changed the clinical scenario of COVID-19. Multisystem inflammatory syndrome in children (MIS-C) has been identified as an important cause of death of children with COVID-19. Perturbations in immunity of T cells, B cells, and mast cells, as well as autoantibodies and metabolic reprogramming may contribute to the long-term symptoms of COVID-19. Atopic diseases, such as allergic asthma and rhinitis, have been shown to be associated with a lower susceptibility and better outcomes of COVID-19. At the beginning of pandemic, EAACI developed guidelines that provided timely information for the management of allergic diseases and preventive measures to reduce transmission in the allergic clinics. The global distribution of COVID-19 vaccines and emerging SARS-CoV-2 variants with reduced pathogenic potential dramatically decreased the morbidity, severity, and mortality of COVID-19. Nevertheless, breakthrough infection remains a challenge for disease control. Hypersensitivity reactions (HSR) to COVID-19 vaccines are low compared to other vaccines, and these were addressed in EAACI statements that provided indications for the management of allergic reactions, including anaphylaxis to COVID-19 vaccines. We have gained a depth knowledge and experience in the over 2 years since the start of the pandemic, and yet a full eradication of SARS-CoV-2 is not on the horizon. Novel strategies are warranted to prevent severe disease in high-risk groups, the development of MIS-C and long COVID.

A document by Marcin Moniuszko. Click on the document to view its contents.

Background: The impact of physical activity (PA) on immune response is a hot topic in exercise immunology, but studies involving asthmatic children are scarce. We examine the level of PA and TV attendance (TVA) in asthmatic children to assess the role on asthma control and immune response to various stimulants. Methods: Weekly PA and daily TVA were obtained from questionnaires at inclusion of the PreDicta study. PBMC cultures were stimulated with phytohemagglutinin (PHA), R848, poly I:C and zymosan. Cytokines were measured and quantified in cell culture supernatants using luminometric multiplex immunofluorescence beads-based assay. Results: Asthmatic preschoolers showed significantly more TVA than their healthy peers (58.6% vs. 41.5% 1-3h daily and only 25.7% vs. 47.2% ≤ 1h daily). Poor asthma control was associated with less frequent PA (75% no or occasional activity in uncontrolled vs. 20% in controlled asthma; 25% ≥ 3x weekly vs. 62%). Asthmatics with increased PA exhibited elevated cytokine levels in response to stimulants, suggesting a readiness of circulating immune cells for type-1, -2 and -17 cytokine release compared to low-PA and high-TVA subjects. Low PA and high TVA were associated with increased proinflammatory cytokines. Proinflammatory cytokines were correlating with each other in in-vitro immune responses of asthmatic children, but not healthy controls. Conclusion: Asthmatic children show more sedentary behavior than healthy subjects, while poor asthma control leads to a decrease in PA. Asthmatic children profit from exercise, as elevated cytokine levels in stimulated conditions indicate an immune system prepared for a strong response in case of infection.

Food allergy is an increasingly common disease worldwide, and is thought to be driven by an uncontrolled type 2 immune response. Current knowledge about the underlying mechanisms that initiate and promote an inappropriate immune response to dietary allergens is limited. Sensitization through the skin in early life is considered to be a key event. Food allergy results from a dysregulated type 2 response to food allergens, characterized by enhanced levels of IgE, IL-4, IL-5 and IL-13 with infiltration of mast cells, eosinophils and basophils during acute reactions. Recent data implies a possible role of innate lymphoid cells (ILCs) in driving food allergy. ILCs represent a group of lymphocytes that lack specific, recombined antigen receptors. They contribute to immune responses not only through the release of cytokines and other mediators, but also by responding to cytokines produced by activated cells in their local microenvironment. Due to their localization at barrier surfaces of the airways, gut and skin, ILCs form a link between the innate and adaptive immunity. This review summarizes recent evidences on how skin and gastrointestinal mucosal immune system contribute to both homeostasis and the development of food allergy, as well as the involvement of ILCs towards inflammatory processes and regulatory mechanisms.