medRxiv - Allergy and Immunology最新文献

{"title":"Single Cell Sequencing of Human Langerhans Cells Identifies Altered Gene Expression Profiles in Patients with Atopic Dermatitis","authors":"Sara M. Tamminga, M. Marlot van der Wal, Elise S. Saager, Lian F. van der Gang, Celeste M. Boesjes, Astrid Hendriks, Yvonne Pannekoek, Marjolein S. de Bruin, Femke van Wijk, Nina M. van Sorge","doi":"10.1101/2024.05.06.24306801","DOIUrl":"https://doi.org/10.1101/2024.05.06.24306801","url":null,"abstract":"Atopic dermatitis (AD) is characterized by dysregulated T cell immunity and skin microbiome dysbiosis with predominance of <em>Staphylococcus aureus</em> (<em>S. aureus</em>). Emerging evidence suggests a role for <em>S. aureus</em> in exacerbating AD skin inflammation. We have previously shown that specific glycosylation of <em>S. aureus</em> cell wall structures amplifies skin inflammation through interaction with Langerhans cells (LCs). However, the role of LCs in AD remains poorly characterized. Here, we performed single cell RNA-sequencing of primary epidermal LCs and dermal T cells isolated from skin biopsies of AD patients and healthy controls, alongside specific glycoanalysis of <em>S. aureus</em> strains isolated from the AD lesions. Our findings reveal four LC subpopulations, including two steady-state clusters (LC1 and LC1_H) and two pro-inflammatory/matured subsets (LC2 and migratory LCs). The latter two subsets were enriched in AD skin. AD LCs showed enhanced expression of C-type lectin receptors, the high-affinity IgE receptor (FcεR1), and activation of prostaglandin and leukotrienes biosynthesis pathways, as well as upregulated transcriptional signatures related to T cell activation pathways and increased expression of CCL17 (specifically LC2) compared to healthy LCs. Correspondingly, T helper 2 and regulatory T cell populations were increased in AD lesions. Our study provides proof-of-concept for a role of LCs in connecting the <em>S. aureus</em>-T cell axis in the AD inflammatory cycle.","PeriodicalId":501527,"journal":{"name":"medRxiv - Allergy and Immunology","volume":"38 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140929981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Demonstration of a Decongestant Effect of “Coldamaris Akut” Compared to Saline Nasal Spray in Participants Suffering from Seasonal Allergic Rhinitis","authors":"Nicole Unger-Manhart, Martina Morokutti-Kurz, Petra Zieglmayer, Patrick Lemell, Markus Savli, René Zieglmayer, Hanna Dellago, Eva Prieschl-Grassauer","doi":"10.1101/2024.05.03.24306805","DOIUrl":"https://doi.org/10.1101/2024.05.03.24306805","url":null,"abstract":"<strong>Purpose</strong> Carrageenan-containing nasal sprays are known to alleviate symptoms of common cold and allergic symptoms by building a barrier against airborne intruders. The objective of this study was to develop a hyperosmolar nasal spray with barrier-forming properties and to demonstrate its decongestant effect in the context of allergic rhinitis.","PeriodicalId":501527,"journal":{"name":"medRxiv - Allergy and Immunology","volume":"10 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140881583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Global associations of maternal hypertensive disorders and offspring allergic disease burden","authors":"Duan Ni, Ralph Nanan","doi":"10.1101/2024.04.29.24306588","DOIUrl":"https://doi.org/10.1101/2024.04.29.24306588","url":null,"abstract":"<strong>Objectives</strong> Maternal hypertensive disorders (MHD) are widespread globally, modifying maternal and fetal immunity, and have been linked to increased allergic diseases in offsprings. Nevertheless, so far, most studies in this field are small-scale and results remain inconclusive.","PeriodicalId":501527,"journal":{"name":"medRxiv - Allergy and Immunology","volume":"30 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140887844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The RESIST Senior Individuals Cohort: Design, participant characteristics and aims","authors":"LM Roesner, KM Gupta, V Kopfnagel, N van Unen, X Jiang, Y Kemmling, J Heise, L Riemann, S Traidl, B Lange, S Castell, KW Sühs, T Illig, T Strowig, Y Li, R Förster, J Huehn, TF Schulz, T Werfel, the RESIST SI Cohort Investigators","doi":"10.1101/2024.04.29.24306533","DOIUrl":"https://doi.org/10.1101/2024.04.29.24306533","url":null,"abstract":"The number of older adults worldwide is growing exponentially. However, while living longer, older individuals are more susceptible to both non-infectious and infectious diseases, at least in part due to alterations of the immune system. Here, we report on a prospective cohort study investigating the influence of age on immune responses and susceptibility to infection. The RESIST Senior Individuals (SI) cohort was established as a general population cohort with a focus on the elderly, enrolling an age- and sex-stratified sample of 650 individuals (n=100 20-39y, n=550 61-94y, 2019-2023, Hannover, Germany). It includes clinical, demographic, and lifestyle data and also extensive biomaterial sampling. Initial insights indicate that the SI cohort exhibits characteristics of the aging immune system and the associated susceptibility to infection, thereby providing a suitable platform for the decoding of age-related alterations of the immune system and unraveling the molecular mechanisms underlying the impaired immune responsiveness in aging populations by exploring comprehensive, unbiased multi-omics datasets.","PeriodicalId":501527,"journal":{"name":"medRxiv - Allergy and Immunology","volume":"88 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140831718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antibody Responses to SARS-Cov-2 among Health Care Workers of a Tertiary Hospital in North-Eastern, Tanzania","authors":"Pendo M Ibrahim, Felix Anthony, Happiness Mshana, Kevin Rwegoshola, Hadija Semvua, Jaffu Chilongola","doi":"10.1101/2024.04.09.24305582","DOIUrl":"https://doi.org/10.1101/2024.04.09.24305582","url":null,"abstract":"<strong>Background</strong> Health Care Workers (HCWs) have been playing crucial role in treating patient with COVID-19. They have a higher occupational risk of contracting the disease than the general population, and a greater chance of them transmitting the disease to vulnerable patients under their care. Given their scarcity and low COVID-19 vaccine acceptance in Africa, it is essential that HCWs are seroprotected and their exposure to COVID-19 minimized. This study was therefore designed to determine IgG antibody response to SARS-CoV-2 among HCWs in North Eastern, Tanzania.","PeriodicalId":501527,"journal":{"name":"medRxiv - Allergy and Immunology","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140581521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hybrid humoral immune response of Pacific Islanders to BNT162b2 vaccination and Delta/Omicron infection: a cohort study","authors":"Catherine Inizan, Adrien Courtot, Chloé Sturmach, Anne-Fleur Griffon, Antoine Biron, Timothée Bruel, Vincent Enouf, Thibaut Demaneuf, Sandie Munier, Olivier Schwartz, Ann-Claire Gourinat, Georges Médevielle, Marc Jouan, Sylvie van der Werf, Yoann Madec, Valérie Albert-Dunais, Myrielle Dupont-Rouzeyrol","doi":"10.1101/2024.04.09.24305559","DOIUrl":"https://doi.org/10.1101/2024.04.09.24305559","url":null,"abstract":"<strong>Background</strong> Pacific Islanders are underrepresented in vaccine efficacy trials. Few studies describe their immune response to COVID-19 vaccination. Yet, this characterization is crucial to re-enforce vaccination strategies adapted to Pacific Islanders singularities.","PeriodicalId":501527,"journal":{"name":"medRxiv - Allergy and Immunology","volume":"47 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140581518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"How dietary landscapes impact food allergy","authors":"Duan Ni, Alistair Senior, Jian Tan, Laurence Macia, Ralph Nanan","doi":"10.1101/2024.04.06.24305435","DOIUrl":"https://doi.org/10.1101/2024.04.06.24305435","url":null,"abstract":"Diets and environments are critical determinants for food allergy development. Harnessing unprecedented epidemiological and nutritional data, we examined the overall dietary environments for common food allergens and their intrinsic nutrient composition. We found that food and macronutrient supplies minimally impacted food allergy prevalence, but higher protein and glycine in food allergens correlated with less allergies. These findings offer new directions in food allergy research and management.","PeriodicalId":501527,"journal":{"name":"medRxiv - Allergy and Immunology","volume":"38 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140581519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systems vaccinology identifies clinical and immunological correlates of SARS-CoV-2 vaccine response in solid-organ transplant recipients","authors":"Nicolas Gemander, Julika Neumann, Rafael Veiga, Isabelle Etienne, Teresa Prezzemolo, Delphine Kemlin, Pieter Pannus, Stéphanie Depickère, Véronique Olislagers, Inès Vu Duc, Alexandra Waegemans, Margaux Gerbaux, Leoni Bücken, Hafid Dahma, Charlotte Martin, Nicolas Dauby, Maria E Goossens, Isabelle Desombere, Carlos P Roca, Mathijs Willemsen, Stanislas Goriely, Alain Le Moine, Arnaud Marchant, Adrian Liston, Stephanie Humblet-Baron","doi":"10.1101/2024.04.05.24305357","DOIUrl":"https://doi.org/10.1101/2024.04.05.24305357","url":null,"abstract":"Solid organ transplant (SOT) recipients are at enhanced risk of adverse outcomes following infectious challenges due to immunosuppressive treatment and additional comorbidities. Unfortunately, SOT recipients are also poor responders to the key medical intervention to preventing infection: vaccines. Here we performed a systems vaccinology study on a cohort of 59 kidney transplant recipients and 31 lung transplant recipients who received the mRNA Pfizer-BioNTech COVID-19 vaccine. Analyzing the immunological status of the patients prior to vaccination, we were able to identify multiple immunological associates of relatively improved vaccine responses following two or three doses of mRNA-based SARS-CoV-2 vaccine. These immunological associates predicted, with 95.0% and 93.3% accuracy, vaccine response after the second and third dose, respectively. Comparison of the immunological associates with vaccine response in SOT recipients revealed two distinct immune configurations: a non-classical configuration, distinct from the immune state of healthy subjects, associated with responses to two doses of mRNA vaccine and that could be mediated partly by the presence of double negative B cell subsets which are more prominently represented in responsive SOT recipients, and a “normalized” configuration, closer to the immune state of healthy subjects, associated with potent antibody responses to three doses of mRNA vaccine. These results suggest that immunosuppression in SOT recipients can result in distinct immune states associated with different trade-offs in vaccine responsiveness. Immune phenotyping of SOT recipients for immune constellation may be an effective approach for identifying patients most at risk of poor vaccine responses and susceptibility to vaccine-preventable diseases.","PeriodicalId":501527,"journal":{"name":"medRxiv - Allergy and Immunology","volume":"51 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140581610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Splice site and de novo mutations can cause mixed gain of function/dominant negative PLCG2-associated immune dysregulation with cold urticaria (CU-PLAID)","authors":"Sophia Renee Chou, Alexis Christine Bailey, Kathleen Christine Baysac, Andrew Oler, Joshua D. Milner, Michael Joseph Ombrello","doi":"10.1101/2024.03.16.24304180","DOIUrl":"https://doi.org/10.1101/2024.03.16.24304180","url":null,"abstract":"Background: Phospholipase Cγ2 (PLCγ2) is an important signaling molecule that receives and transmits signals from various cell surface receptors in most hematopoietic lineages. Variants of PLCG2 cause PLCγ2-associated immune dysregulation (PLAID), a family of conditions that are classified by mutational effect. PLAID with cold urticaria (CU-PLAID) is caused by in-frame deletions of PLCG2 that are dominant negative at physiologic temperatures but become spontaneously active at sub-physiologic temperatures.\u0000Objective: To identify genetic lesions causing PLAID by combining RNA sequencing of full-length PLCG2 with whole genome sequencing. Methods: We studied nine probands with antibody deficiency and a positive evaporative cooling test, together with two known CU-PLAID patients and three healthy subjects. Illumina sequencing was performed on full-length PLCG2 cDNA synthesized from peripheral blood mononuclear cell RNA and whole genome sequencing was used to identify genetic lesions. Novel alternate transcripts were overexpressed in the Plcg2-deficient DT40 cell overexpression system. ERK phosphorylation was quantified by flow cytometry with and without BCR crosslinking.\u0000Results: Two probands expressed novel alternative transcripts of PLCG2 with in-frame deletions. The first, expressing PLCG2 without exons 18-19, carried a splice site mutation in intron 19. The second, expressing PLCG2 without exons 19-22, carried a 14kb de novo deletion of PLCG2. DT40 cells overexpressing the exon 18-19 or exon 19-22 deletions failed to phosphorylate ERK in response to BCR crosslinking.\u0000Conclusion: In addition to autosomal dominant genomic deletions, de novo deletions and splice site mutations of PLCG2 can also cause CU-PLAID. All of these can be identified by cDNA-based sequencing.","PeriodicalId":501527,"journal":{"name":"medRxiv - Allergy and Immunology","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140171500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expanded T cell clones with lymphoma driver somatic mutations in refractory celiac disease","authors":"Mandeep Singh, Raymond HY Louie, Jerome Samir, Matthew Field, Claire Milthorpe Milthorpe, Thiruni Adikari, Joseph Mackie, Ellise Roper, Megan Faulks, Katherine JL Jackson, Andrew Calcino, Melinda Y Hardy, Piers Blombery, Timothy G Amos, Ira W Deveson, Scott A Read, Dmitry Shek, Antoine Guerin, Cindy S Ma, Stuart G Tangye, Antonio Di Sabatino, Marco Lenti, Alessandra Pasini, Rachele Ciccocioppo, Golo Ahlenstiel, Dan Suan, Jason A Tye-Din, Christopher C Goodnow, Fabio Luciani","doi":"10.1101/2024.03.17.24304320","DOIUrl":"https://doi.org/10.1101/2024.03.17.24304320","url":null,"abstract":"Intestinal inflammation continues in a subset of celiac disease (CD) patients despite a gluten-free diet. Here, by applying multiomic single cell analysis to duodenal biopsies, we find low-grade malignancies with lymphoma driver mutations in refractory CD type 2 (RCD2) patients comprise surface CD3 negative (sCD3-) lymphocytes stalled at an innate lymphoid cell (ILC) - progenitor T cell stage undergoing extensive TCR recombination. In people with refractory CD type 1 (RCD1), who currently lack explanation, we discover sCD3+ T cells with lymphoma driver mutations forming large clones displaying inflammatory and cytotoxic molecular profiles in 6 of 10 individuals, and a single small clone in 1 of 4 active recently diagnosed CD cases. Accumulation of driver-mutated T cells and their sCD3- progenitors may explain chronic, non-responsive autoimmunity.","PeriodicalId":501527,"journal":{"name":"medRxiv - Allergy and Immunology","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140171503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}