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A GWAS of ACE Inhibitor-Induced Angioedema in a South African Population. medRxiv. Allergy Immunol. Pub Date : 2024-09-15 Jacquiline Wangui Mugo, Cascia Day, Ananyo Choudhury, Maria Deetlefs, Robert Freercks, Sian Geraty, Angelica Panieri, Christian Cotchbos, Melissa Ribeiro, Adelein Engelbrecht, Lisa K. Micklesfield, Michèle Ramsay, Sarah Pedretti, Jonny Peter
Background: Angiotensin-converting enzyme inhibitor-induced angioedema (AE-ACEI) is a life-threatening adverse event and, globally, the commonest cause of emergency presentations with angioedema. Several large genome-wide association studies (GWAS) have found genomic associations with AE-ACEI. However, despite African Americans having a 5-fold increased risk of AE-ACEI, there are no published GWAS
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Patterns and functional consequences of antibody speciation in maternal-fetal transfer of coronavirus-specific humoral immunity medRxiv. Allergy Immunol. Pub Date : 2024-09-13 Andrew P Hederman, Hannah M Brookes, Harini Natarajan, Leo Heyndrickx, Kevin K. Arien, Joshua A Weiner, Amihai Rottenstreich, Gila Zarbiv, Dana Wolf, Tessa Goetghebuer, Arnaud Marchant, Margaret E Ackerman
Maternal antibodies serve as a temporary form of inherited immunity, providing humoral protection to vulnerable neonates. Whereas IgG is actively transferred up a concentration gradient via the neonatal Fc Receptor (FcRn), maternal IgA and IgM are typically excluded from fetal circulation. Further, not all IgG molecules exhibit the same transfer efficiency, being influenced by subclass, Fab and Fc
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A novel UNC93B1 gain-of-function mutation leads to TLR7 and TLR8 hyperactivation and systemic lupus erythematosus medRxiv. Allergy Immunol. Pub Date : 2024-09-13 Xu Han, RuoRan Wang, Seza Ozen, Qintao Wang, Wei Dong, Yi Zeng, Ouyuan Xu, Seher Şenar, Li Guo, Ying Gu, Huanming Yang, Xiaomin Yu, Panfeng Tao, Qing Zhou
Dysfunctions in nucleic acid-sensing Toll-like receptors (TLRs) disrupt nucleic acid tolerance, leading to systemic lupus erythematosus (SLE). Here, we report a novel homozygous gain-of-function p.R95L mutation in the TLR chaperone protein UNC93B1 in an SLE patient. Bulk and single-cell transcriptional analysis of the patient's peripheral blood mononuclear cells (PBMCs) revealed significantly elevated
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The Healthy Human Global Project - Hong Kong : a community-based cross-sectional study of a healthy Asian population medRxiv. Allergy Immunol. Pub Date : 2024-09-12 Rex L Hung, Wilson W Ng, Peter K Chung, Ashley B S Li, Theodora H Y Luk, Rosanna Fong, Anna Lee, Raina Mok, Hebronson Yung, Vera Tse, Raven Cheng, Amandine Schneider, Rachel L Telford, Florian Dubois, Elsa Bourayou, Milieu Interieur, Rafael De Andrade Moral, Jean Marc Doisne, Milena Hasan, Gabriel M Leung, Michael Y Ni, Michael Tse, Malik Peiris, James Di Santo, Roberto Bruzzone, Vincent Rouilly, Darragh
Immune responses are highly variable from one individual to another, with this variability determined by factors such as age, sex, genetics and environment, which also affect physical and mental well-being. Systems immunology studies have been applied to human cohort studies to better understand these effects, but most are performed in Western populations of mostly European ancestry, neglecting the
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Investigating Chemokine-Induced NF-κB Activation in Retinal Cells and Its Contribution to Age-Related Macular Degeneration Pathogenesis: A Systematic Review medRxiv. Allergy Immunol. Pub Date : 2024-09-08 Ifrah Siddiqui, Nabeel Ahmad Khan, Fatima Ahmad, Maham Nawaz, Almas Naeem, Muhammad Usaid Khalid, Usman Haroon Mirza, Hamza Ali Danish, Syed Saqib Khalid
Objective: To investigate the roles of chemokines in activating the NF-κB signaling pathway in retinal pigment epithelium (RPE) and photoreceptor cells, and their contribution to the pathogenesis of age-related macular degeneration (AMD). Background: AMD is a leading cause of vision loss in older adults, driven by chronic inflammation and oxidative stress. The NF-κB transcription factor plays a key
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Immunotoxic Effects in Children Resulting from Prenatal and Early Childhood Exposure to Pesticides: Protocol of a Systematic Review and Meta-Analysis medRxiv. Allergy Immunol. Pub Date : 2024-09-06 Moustafa Sherif, Aya Darwish, Balazs Adam
Background Pesticides, commonly employed in both agricultural and domestic environments, have been associated with disturbing the balance of the immune system during prenatal and early childhood phases of development. This disturbance has the potential to result in various outcomes such as autoimmunity, immunosuppression, inflammation, hypersensitivity, tissue damage, and overall alterations in immune
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A systematic review of low-dose interleukin-2 for the treatment of systemic lupus erythematosus medRxiv. Allergy Immunol. Pub Date : 2024-09-06 Lara Bader, Onur Boyman, Miro E. Raeber
Background Low-dose interleukin-2 (IL-2) shows promise as a treatment for restoring functional and numerical deficits of regulatory T (Treg) cells in patients with various autoimmune diseases. Several clinical trials testing low-dose IL-2 in systemic lupus erythematosus (SLE) have been completed, with a comprehensive review of these trials currently lacking.
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Low-dose interleukin-2 in birch pollen allergy: a phase-2 randomized double-blind placebo-controlled trial medRxiv. Allergy Immunol. Pub Date : 2024-09-04 M Rosenzwajg, A Gherasim, F Dietsch, M. Beck, N Domis, R Lorenzon, Yannick Chantran, B Bellier, E Vicaut, A Soria, F De Blay, D Klatzmann
Background Regulatory T cells (Tregs) are pivotal in immune tolerance to allergens. Low-dose IL-2 (IL-2LD) expands and activates Tregs. We assessed IL-2LD efficacy for controlling clinical responses to allergen exposures.
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Deciphering autoantibody landscape of systemic sclerosis through systems-based approach: insights from a B-cell depletion clinical trial medRxiv. Allergy Immunol. Pub Date : 2024-09-03 Kazuki M Matsuda, Satoshi Ebata, Kazuhiro Iwadoh, Hirohito Kotani, Teruyoshi Hisamoto, Ai Kuzumi, Takemichi Fukasawa, Asako Yoshizaki-Ogawa, Shinichi Sato, Ayumi Yoshizaki
Systemic sclerosis (SSc) is a progressive fibrotic disorder with a high mortality rate, characterized by extensive autoantibody production. Despite recent advancements, effective treatments remain limited. Rituximab (RTX), a B-cell depleting agent, has shown promise in clinical trials. The DESIRES trial highlighted the reduction in modified Rodnan Skin Score (mRSS) and the association between serum
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FACS-based detection of extracellular ASC specks from NLRP3 inflammasomes in inflammatory diseases medRxiv. Allergy Immunol. Pub Date : 2024-08-26 Joanne Topping, Samuel Lara-Reyna, Alice I Ibbotson, Heledd Jarosz-Griffiths, Leon Chang, James A Poulter, Daniel G Peckham, Michael F Mcdermott, Sinisa Savic, ImmunAID Consortium
The apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) is crucial for inflammasome assembly and activation of several inflammasomes, including NLRP3. ASC aggregates are detected in human sera post pyroptotic cell death, but their inflammasome origin remains unclear. This study aimed to develop a method to detect ASC aggregates originating from NLRP3 inflammasomes
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Investigating chromosomal radiosensitivity in inborn errors of immunity: insights from DNA repair disorders and beyond. medRxiv. Allergy Immunol. Pub Date : 2024-08-20 Elien Beyls, Evi Duthoo, Lynn Backers, Karlien Claes, RAPID clinicians, Marieke De Bruyne, Lore Pottie, Victoria Bordon, Carolien Bonroy, Simon J Tavernier, Kathleen BM Claes, Anne Vral, Ans Baeyens, Filomeen Haerynck
Human inborn errors of immunity (IEI) represent a diverse group of genetic disorders affecting the innate and/or adaptive immune system. Some IEI entities comprise defects in DNA repair factors, resulting in (severe) combined immunodeficiencies, bone marrow failure, predisposition to malignancies, and potentially result in radiosensitivity (RS). While other IEI subcategories such as common variable
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3D chromatin-based variant-to-gene maps across 57 human cell types reveal the cellular and genetic architecture of autoimmune disease susceptibility medRxiv. Allergy Immunol. Pub Date : 2024-08-12 Khanh Bao Trang, Prabhat Sharma, Laura Cook, Zachary Mount, Rajan M Thomas, Nikhil N Kulkarni, Matthew C Pahl, James A Pippin, Chun Su, Klaus H Kaestner, Joan M O'Brien, Yadav Wagley, Kurt D Hankenson, Ashley Jermusyk, Jason W Hoskins, Laufey T Amundadottir, Mai Xu, Kevin M Brown, Stewart A Anderson, Wenli Yang, Paul M Titchenell, Patrick Seale, Babette S Zemel, Alessandra Chesi, Neil Romberg, Megan
A portion of the genetic basis for many common autoimmune disorders has been uncovered by genome-wide association studies (GWAS), but GWAS do not reveal causal variants, effector genes, or the cell types impacted by disease-associated variation. We have generated 3D genomic datasets consisting of promoter-focused Capture-C, Hi-C, ATAC-seq, and RNA-seq and integrated these data with GWAS of 16 autoimmune
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Alterations in secondary structure and binding affinity from mutations in the interleukin-1 receptor antagonist medRxiv. Allergy Immunol. Pub Date : 2024-08-12 Joshua Pillai
Deficiency of Interleukin-1 receptor antagonist (DIRA) is a rare autosomal recessive autoinflammatory disorder that occurs during the neonatal period, manifesting a spectrum of symptoms including but not limited to osteomyelitis and pustulosis. This disease results from loss-of-function mutations in the IL1RN gene, encoding the IL-1 receptor antagonist (IL-1Ra). The dysfunction of IL-1Ra may arise
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Cervical mucosal inflammation expands functional polymorphonuclear myeloid-derived suppressor cells medRxiv. Allergy Immunol. Pub Date : 2024-08-09 Daan KJ Pieren, Aleix Benítez-Martínez, Vicente Descalzo, Maider Arando, Patricia Álvarez-López, Jorge N Garcia-Perez, Núria Massana, Júlia Castellón, Yannick Hoyos-Mallecot, Daniel Alvárez-Sierra, Clara Ramírez-Serra, Nuria Laia Rodriguez, Laura Mañalich-Barrachina, Cristina Centeno-Mediavilla, Josep Castellví, Vicenç Falcó, Maria J Buzón, Meritxell Genescà
The mucosal immune system plays a fundamental role in maintaining microbial balance. Microbial imbalance in the female genital tract increases the risk for adverse health outcomes in women and may increase susceptibility to genital tract infections. Among different relevant immune subsets, myeloid-derived suppressor cells (MDSCs) remain understudied in the context of female genital tract conditions
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Causal modeling in large-scale data to improve identification of adults at risk for combined and common variable immunodeficiencies medRxiv. Allergy Immunol. Pub Date : 2024-08-09 Giorgos Papanastasiou, Marco Scutari, Raffi Tachdjian, Vivian Hernandez-Trujillo, Jason Raasch, Kaylyn Billmeyer, Nikolay V Vasilyev, Vladimir Ivanov
Combined immunodeficiencies (CID) and common variable immunodeficiencies (CVID), prevalent yet substantially underdiagnosed primary immunodeficiency disorders, necessitate improved early detection strategies. Leveraging large-scale electronic health record (EHR) data from four nationwide US cohorts, we developed a novel causal Bayesian Network (BN) model to unravel the complex interplay of antecedent
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Sequential mosaic variants in KRAS and STAT5B associated with a mixed phenotype of two acquired errors of immunity medRxiv. Allergy Immunol. Pub Date : 2024-08-08 Julia Forkgen, Etienne Masle-Farquhar, Yves Fontaine, Amanda Russell, Shannon Ji, Timothy J Peters, Zhen Qiao, Michael Geaghan, Katherine JL Jackson, Jillian M Hammond, Ira W Deveson, Clementine David, Daniel A Lemberg, Nitin Gupta, Noemi Fuentes-Bolanos, Satu Mustjoki, Vivian Hwa, Stuart G Tangye, Paul E Gray, Owen M Siggs
Mosaic genetic variation has been implicated in the pathogenesis of both malignant and non-malignant immunological disease. Here, we report a unique case of postnatal acquisition of a gain-of-function (GoF) KRAS variant, with an additional GoF STAT5B variant, in a woman with inflammatory bowel disease, splenomegaly, thrombocytopenia, bronchiectasis, monocytosis, and eosinophilia. Targeted amplicon
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SLC27A2 as a molecular marker of impaired epithelium in chronic rhinosinusitis with nasal polyps medRxiv. Allergy Immunol. Pub Date : 2024-08-07 Jaewoo Park, Jung Yeon Jang, Jeong Heon Kim, Se Eun Yi, Yeong Ju Lee, Myeong Sang Yu, Yoo-Sam Chung, Yong Ju Jang, Ji Heui Kim, Kyuho Kang
Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a complex disease characterized by multiple inflammatory endotypes. Although recent progress has been made in endotype-based classification, developing tailored therapeutic strategies for CRSwNP remains challenging. This study aimed to optimize therapeutic outcomes in CRSwNP by identifying potential molecular markers. Methods: We utilized
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ATRIP deficiency impairs the replication stress response and manifests as microcephalic primordial dwarfism and immunodeficiency. medRxiv. Allergy Immunol. Pub Date : 2024-07-23 Evi Duthoo, Elien Beyls, Lynn Backers, Thorkell Gudjónsson, Peiquan Huang, Leander Jonckheere, Sebastian Riemann, Bram Parton, Likun Du, Veronique Debacker, Marieke De Bruyne, Levi Hoste, Ans Baeyens, Anne Vral, Eva Van Braeckel, Jens Staal, Geert Mortier, Tessa Kerre, Qiang Pan-Hammarström, Claus S Sørensen, Filomeen Haerynck, Kathleen BM Claes, Simon J Tavernier
ATR (Ataxia Telangiectasia and Rad3-related) kinase and its interacting protein ATRIP orchestrate the replication stress response. Two patients of independent ancestry with microcephaly, primordial dwarfism, and recurring infections were found to be homozygous for splice donor site variants of ATRIP exon 5, resulting in ATRIP deficiency. The c.829+5G>T patient exhibited autoimmune hemolytic anemia
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Epigenetic Signatures of Asthma: A Comprehensive Study of DNA Methylation and Clinical Markers medRxiv. Allergy Immunol. Pub Date : 2024-07-23 Austin J Van Asselt, Jeffrey J Beck, Brandon N Johnson, Casey T Finnicum, Noah Kallsen, Sarah Viet, Patricia Huizenga, Lannie Ligthart, Jouke-Jan Hottenga, René Pool, Anke H. Maitland-van der Zee, Susanne J Vijverberg, Eco de Geus, Dorret I Boomsma, Erik A Ehli, Jenny van Dongen
Background: Asthma, a complex respiratory disease, presents with inflammatory symptoms in the lungs, blood, and other tissues. We investigated the relationship between DNA methylation and 35 clinical markers of asthma. The Illumina Infinium EPIC v1 methylation array was used to evaluate 742,442 CpGs in whole blood samples from 319 participants. They were part of the Netherlands Twin Register from families
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Geranylgeraniol supplementation leads to an improvement in inflammatory parameters and reversal of the disease specific protein signature in patients with hyper-IgD syndrome medRxiv. Allergy Immunol. Pub Date : 2024-07-18 Anna Sediva, Martin Orlicky, Petra Vrabcova, Adam Klocperk, Tomas Kalina, Hideji Fujiwara, Fong-Fu Hsu, Monika Bambouskova
Mevalonate kinase (MVK) deficiency, a rare autosomal recessive disease, significantly impacts metabolism and immunity, leading to mevalonic aciduria in severe cases and hyper-IgD syndrome (HIDS) in partial deficiency. These conditions arise due to disruptions in the mevalonate pathway, which is essential metabolic pathway responsible for the synthesis of non-sterol isoprenoids and other molecules.
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Enhanced Gut Microbiome Capacity for Amino Acid Metabolism is associated with Peanut Oral Immunotherapy Failure medRxiv. Allergy Immunol. Pub Date : 2024-07-15 Mustafa Ozcam, Din L Lin, Chhedi L Gupta, Allison Li, Lisa M. Wheatley, Carolyn H. Baloh, Srinath Sanda, Stacie M. Jones, Susan V. Lynch
Peanut Oral Immunotherapy (POIT) holds promise for remission of peanut allergy, though treatment is protracted and successful in only a subset of patients. Because the gut microbiome is linked to food allergy, we sought to identify fecal microbial predictors of POIT efficacy and to develop mechanistic insights into treatment response. Longitudinal functional analysis of the fecal microbiome of children
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MENSA, a Media Enriched with Newly Synthesized Antibodies, to Identify SARS-CoV-2 Persistence and Latent Viral Reactivation in Long-COVID medRxiv. Allergy Immunol. Pub Date : 2024-07-07 Natalie S. Haddad, Andrea Morrison-Porter, Hannah Quehl, Violeta Capric, Pedro A. Lamothe, Fabliha Anam, Martin C. Runnstrom, Alex D. Truong, Adviteeya N. Dixit, Matthew C. Woodruff, Anting Chen, Jiwon Park, Doan C. Nguyen, Ian Hentenaar, Caroline Y. Kim, Shuya Kyu, Brandon Stewart, Elizabeth Wagman, Hannah Geoffroy, Daniel Sanz, Kevin S. Cashman, Richard P. Ramonell, Monica Cabrera-Mora, David N.
Post-acute sequelae of SARS-CoV-2 (SARS2) infection (PASC) is a heterogeneous condition, but the main viral drivers are unknown. Here, we use MENSA, Media Enriched with Newly Synthesized Antibodies, secreted exclusively from circulating human plasmablasts, to provide an immune snapshot that defines the underlying viral triggers. We provide proof-of-concept testing that the MENSA technology can capture
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PGAP3 regulates human bronchial epithelial cell mRNAs present in asthma and respiratory virus reference data sets medRxiv. Allergy Immunol. Pub Date : 2024-07-06 Eric Leslie, Marina Miller, Allison LaFuze, Sofya Svyatskaya, Gil-Soon Choi, David H Broide
PGAP3 is a glycosylphosphatidylinositol (GPI) phospholipase gene localized within chromosome 17q12-21, a region highly linked to asthma. Although much is known about the function of other chromosome 17q12-21 genes expressed at increased levels in bronchial epithelium such as ORMDL3 and GSDMB, little is known about the function of increased PGAP3 expression in bronchial epithelium in the context of
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A multimorphic variant in ThPOK causes a novel human disease characterized by T cell abnormalities, immunodysregulation, allergy, and fibrosis medRxiv. Allergy Immunol. Pub Date : 2024-06-28 Maryam Vaseghi-Shanjani, Mehul Sharma, Pariya Yousefi, Simran Samra, Kaitlin U. Laverty, Arttu Jolma, Rozita Razavi, Ally H. W. Yang, Mihai Albu, Liam Golding, Anna F. Lee, Ryan Tan, Phillip A. Richmond, Marita Bosticardo, Jonathan H. Rayment, Connie L. Yang, Kyla J. Hildebrand, Rae Brager, Michelle K. Demos, Yu Lung Lau, Luigi D. Notarangelo, Timothy R. Hughes, Catherine M. Biggs, Stuart E. Turvey
ThPOK is best known as a regulator of CD4+ T cell lineage commitment, although it was initially cloned as a suppressor of collagen expression in the skin. The role of ThPOK has not been formally established in humans since individuals with damaging variants in ThPOK have not yet been identified. Here, we report the first case of a human with a damaging heterozygous de novo variant in ThPOK causing
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COVID-19 vaccination atlas: an integrative systems vaccinology approach medRxiv. Allergy Immunol. Pub Date : 2024-06-28 Wasim Aluísio Prates-Syed, Dennyson Leandro M Fonseca, Shahab Zaki Pour, Igor Salerno Filgueiras, Lena F Schimke, Aline Aparecida Lira, Nelson Cortes de Oliveira, Jaqueline Dinis Queiroz Silva, Evelyn Carvalho, Tania Geraldine Churasacari-Vinces, Lorena C S Chaves, Gerhard Wunderlich, Ricardo Durães-Carvalho, Niels O S Câmara, Haroldo Dutra Dias, Hans D Ochs, Jose E Krieger, Helder I Nakaya, Otavio
COVID-19 vaccinations have significantly controlled the pandemic. To elucidate their impact on the immune system, we developed a COVID-19 vaccination atlas through an integrative systems vaccinology approach. Our atlas includes both healthy individuals and those infected with or without prior vaccination, and covers the administration of five vaccines in different regimens: Covilo®, Zifivax®, Vaxzebria®
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Temporal multi-omic analysis of COVID-19 in end-stage kidney disease medRxiv. Allergy Immunol. Pub Date : 2024-06-24 Emily Stephenson, Erin Macdonald-Dunlop, Lisa M Dratva, Rik G.H. Lindeboom, Zewen Kelvin Tuong, Win Min Tun, Norzawani B Buang, Stephane Ballereau, Mia Cabantaus, Ana Penalver, Elena Prigmore, John R Ferdinand, Benjamin J Stewart, Jack Gisby, Talat Malik, Candice L Clarke, Nicholas Medjeral-Thomas, Maria Prendecki, Stephen McAdoo, Anais Portet, Michelle Willicombe, Eleanor Sandhu, Matthew C Pickering
Patients with end-stage kidney disease (ESKD) are at high risk of severe COVID-19. We performed longitudinal single cell multi-omic immune profiling of ESKD patients with COVID-19, sampled during two waves of the pandemic. Uniquely, for a subset of patients, we obtained samples before and during acute infection, allowing intra-individual comparison. Using single-cell transcriptome, surface proteome
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Wastewater-Based Analysis of Antihistamines to Investigate Pollinosis Symptom Burden at Population-Scale medRxiv. Allergy Immunol. Pub Date : 2024-06-21 Stephan Baumgartner, Michelle Salvisberg, Bernard Clot, Benoit Crouzy, Peter Schmid-Grendelmeier, Heinz Singer, Christoph Ort
Background: Pollinosis, or hay fever, is the most prevalent allergic disorder. Assessing the impact of real-world pollen exposure on symptoms remains challenging due to the extensive efforts required at the patient level. Objectives: We explore the potential of wastewater-based epidemiology (WBE) to investigate the impact of exposure to specific pollen taxa on symptoms and to assess self-medication
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A causal link between autoantibodies and neurological symptoms in long COVID medRxiv. Allergy Immunol. Pub Date : 2024-06-19 Keyla Santos Guedes de Sa, Julio Silva, Rafael Bayarri-Olmos, Ryan Brinda, Robert Alec Rath Constable, Patricia A. Colom Diaz, Dong-il Kwon, Gisele Rodrigues, Li Wenxue, Christopher Baker, Bornali Bhattacharjee, Jamie Wood, Laura Tabacof, Yansheng Liu, David Putrino, Tamas L. Horvath, Akiko Iwasaki
Acute SARS-CoV-2 infection triggers the generation of diverse and functional autoantibodies (AABs), even after mild cases. Persistently elevated autoantibodies have been found in some individuals with long COVID (LC). Using a >21,000 human protein array, we identified diverse AAB targets in LC patients that correlated with their symptoms. Elevated AABs to proteins in the nervous system were found in
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The Cystic Fibrosis Transmembrane Regulator Controls Tolerogenic Responses to Food Allergens in Mice and Humans medRxiv. Allergy Immunol. Pub Date : 2024-06-18 Marc Emmenegger, Chryssa Zografou, Yile Dai, Laura R. Hoyt, Ravindra Gudneppanavar, Andra Chincisan, Hubert Rehrauer, Falko J. Noé, Natalia Zajac, Georg Meisl, Matthias M. Schneider, Hang Nguyen, Katja Höpker, Tuomas P. J. Knowles, Mireia Sospedra, Roland Martin, Aaron M. Ring, Stephanie Leeds, Stephanie C. Eisenbarth, Marie E. Egan, Emanuela M. Bruscia, Adriano Aguzzi
IgE antibodies against the allergen Ara-h2 can cause life-threatening anaphylaxis upon exposure to peanuts. Desensitization strategies aim at inducing IgG responses against Ara-h2 which may compete with anaphylactogenic IgE. Here we assessed anti-Ara-h2 titers in an unselected cohort of 24,536 adult patients admitted to a general hospital for disparate medical reasons. Surprisingly, adult (n=177) and
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IP10 levels refine severity prognostication in COVID-19 and implicate causes of clinical deterioration: lessons for pandemic preparedness medRxiv. Allergy Immunol. Pub Date : 2024-06-16 Abhishek Das, Jia Wei, Duncan McKenzie, Luke B Snell, Shruthi Sasidharan, Pierre Vantourout, Iva Zlatareva, Blair Merrick, Benjamin Thomas, Vasista Adiga, Khiyam Hussain, Rahul Batra, Daniel Davies, Jia Su, Karen Bisnauthsing, Lauren Martinez, Asma Ahmed, Hima Bindhu, Nirutha Chetan, Maria Macrina, Himanshu Tripathi, Geraldine O'Hara, Cassandra Fairhead, Gabija Drazdauskaite, Helen Lock, Mary Dias
Summary Background Emerging pandemics place immense strains on healthcare systems that may be ameliorated by rapid development of biomarkers whose measurements may predict disease severity and additionally inform about disease causation. Conspicuously, such routine measures rarely include immunological cytokines or chemokines, despite their contributions to host protection and immunopathology. Methods
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Identification of an ANCA-Associated Vasculitis Cohort Using Deep Learning and Electronic Health Records medRxiv. Allergy Immunol. Pub Date : 2024-06-10 Liqin Wang, John Novoa-Laurentiev, Claire Cook, Shruthi Srivatsan, Yining Hua, Jie Yang, Eli Miloslavsky, Hyon K. Choi, Li Zhou, Zachary S. Wallace
Background ANCA-associated vasculitis (AAV) is a rare but serious disease. Traditional case-identification methods using claims data can be time-intensive and may miss important subgroups. We hypothesized that a deep learning model analyzing electronic health records (EHR) can more accurately identify AAV cases.
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Proteome-wide autoantibody screening and holistic autoantigenomic analysis unveil COVID-19 signature of autoantibody landscape medRxiv. Allergy Immunol. Pub Date : 2024-06-08 Kazuki M Matsuda, Yoshiaki Kawase, Kazuhiro Iwadoh, Makoto Kurano, Yutaka Yatomi, Koh Okamoto, Kyoji Moriya, Hirohito Kotani, Teruyoshi Hisamoto, Ai Kuzumi, Takemichi Fukasawa, Asako Yoshizaki-Ogawa, Masanori Kono, Tomohisa Okamura, Hirofumi Shoda, Keishi Fujio, Kei Yamaguchi, Taishi Okumura, Chihiro Ono, Yuki Kobayashi, Ayaka Sato, Ayako Miya, Naoki Goshima, Rikako Uchino, Yumi Murakami, Hiroshi Matsunaka
This study presents “aUToAntiBody Comprehensive Database (UT-ABCD)”, a proteome-wide catalog of autoantibody profiles in 284 human individuals. The subjects included patients diagnosed with Coronavirus disease 2019 (COVID-19), systemic sclerosis (SSc), systemic lupus erythematosus (SLE), anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV), atopic dermatitis (AD), as well as healthy controls
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Dupilumab dampens mucosal type 2 response during acetylsalicylic acid challenge in N-ERD patients medRxiv. Allergy Immunol. Pub Date : 2024-06-07 J. Eckl-Dorna, C. Morgenstern, K. Poglitsch, T. Arnoldner, K. Gangl, T. Bartosik, N.J. Campion, A. Tu, V. Stanek, S. Schneider, C. Bangert
Rationale Non-steroidal anti-inflammatory drug-exacerbated respiratory disease (N-ERD) is characterized by the clinical triad of hypersensitivity to NSAIDs, nasal polyposis, and asthma. The cells and mediators causing acute symptoms when driving the hypersensitivity reaction to acetylsalicylic acid (ASA) ingestion, remain poorly defined.
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Consistent Multi-Omic Relationships Uncover Molecular Basis of Pediatric Asthma IgE Regulation medRxiv. Allergy Immunol. Pub Date : 2024-06-06 Tara Eicher, Rachel S. Kelly, John Braisted, Jalal K. Siddiqui, Juan Celedón, Clary Clish, Robert Gerszten, Scott T. Weiss, Michael McGeachie, Raghu Machiraju, Jessica Lasky-Su, Ewy A. Mathé
Serum total immunoglobulin E levels (total IgE) capture the state of the immune system in relation to allergic sensitization. High levels are associated with airway obstruction and poor clinical outcomes in pediatric asthma. Inconsistent patient response to anti-IgE therapies motivates discovery of molecular mechanisms underlying serum IgE level differences in children with asthma. To uncover these
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Tafazzin regulates neutrophil maturation and inflammatory response medRxiv. Allergy Immunol. Pub Date : 2024-06-05 Przemysław Zakrzewski, Christopher M. Rice, Kathryn Fleming, Drinalda Cela, Sarah J. Groves, Fernando Ponce, Willem Gibbs, Kiran Roberts, Tobias Pike, Douglas Strathdee, Eve Anderson, Angela H. Nobbs, Ashley Toye, Colin Steward, Borko Amulic
Barth syndrome (BTHS) is a rare genetic disease caused by mutations in the TAFAZZIN gene. It is characterized by neutropenia, cardiomyopathy and skeletal myopathy. Neutropenia in BTHS is associated with life-threatening infections, yet there is little understanding of the molecular and physiological causes of this phenomenon. We combined bone marrow analysis, CRISPR/Cas9 genome editing in hematopoietic
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ACK1 and BRK non-receptor tyrosine kinase deficiencies are associated with familial systemic lupus and involved in efferocytosis medRxiv. Allergy Immunol. Pub Date : 2024-06-05 Stephanie Guillet, Tomi Lazarov, Natasha Jordan, Bertrand Boisson, Maria Tello, Barbara Craddock, Ting Zhou, Chihiro Nishi, Rohan Bareja, Hairu Yang, Frederic Rieux-Laucat, Rosa Irene Fregel Lorenzo, Sabrina D. Dyall, David Isenberg, David D’Cruz, Nico Lachmann, Olivier Elemento, Agnes Viale, Nicholas D. Socci, Laurent Abel, Shigekazu Nagata, Morgan Huse, W. Todd Miller, Jean-Laurent Casanova, Frederic
Systemic Lupus Erythematosus (SLE) is an autoimmune disease, the pathophysiology and genetic basis of which are incompletely understood. Using a forward genetic screen in multiplex families with systemic lupus erythematosus (SLE) we identified an association between SLE and compound heterozygous deleterious variants in the non-receptor tyrosine kinases (NRTKs) ACK1 and BRK. Experimental blockade of
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Metabolomics of IgE-Mediated Food Allergy and Oral Immunotherapy Outcomes based on Metabolomic Profiling medRxiv. Allergy Immunol. Pub Date : 2024-06-01 Yamini V. Virkud, Jennifer N. Styles, Rachel S. Kelly, Sarita U. Patil, Bert Ruiter, Neal P. Smith, Clary Clish, Craig E. Wheelock, Juan C. Celedón, Augusto A. Litonjua, Supinda Bunyavanich, Scott T. Weiss, Erin S. Baker, Jessica A. Lasky-Su, Wayne G. Shreffler
Background The immunometabolic mechanisms underlying variable responses to oral immunotherapy (OIT) in patients with IgE-mediated food allergy are unknown.
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Volume and Distribution of White Matter Hyperintensities in Rheumatoid Arthritis and Ulcerative Colitis Patients medRxiv. Allergy Immunol. Pub Date : 2024-05-31 Jennifer G. Cox, James H. Cole, Matthew J. Kempton, Steven C. R. Williams, Marius de Groot
Brain white matter disruptions have been implicated in contributing to fatigue, brain fog and other central symptoms commonly reported in inflammatory diseases. In this study, we included 252 RA patients with 756 age and sex matched controls and 240 UC patients with 720 age and sex matched controls using the UK Biobank imaging dataset. We looked for differences in total volume of white matter hyperintensities
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Dengue NS1 interaction with lipids alters its pathogenic effects on monocyte derived macrophages medRxiv. Allergy Immunol. Pub Date : 2024-05-27 Shashika Dayarathna, Bhagya Senadheera, Chandima Jeewandara, Madushika Dissanayaka, Farha Bary, Graham S. Ogg, Gathsaurie Neelika Malavige
Background While dengue NS1 antigen has been shown to be associated with disease pathogenesis in some studies, it has not been linked in other studies, with the reasons remaining unclear. NS1 antigen levels in acute dengue are often associated with increased disease severity, but there have been a wide variation in results based on past dengue infection and infecting dengue virus (DENV) serotype. As
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Exploring the secretion of immunogenic gluten peptides in breast milk from celiac and non celiac mothers medRxiv. Allergy Immunol. Pub Date : 2024-05-22 Ángela Ruiz-Carnicer, Verónica Segura, María de Lourdes Moreno, Cristóbal Coronel-Rodríguez, Carolina Sousa, Isabel Comino
Background Exposure to antigens is crucial for child immune system development, aiding disease prevention and promoting infant health. Some common food antigen proteins are found in human breast milk. However, it is unclear whether gluten antigens linked to celiac disease (CD) are transmitted through breast milk, potentially impacting the development of the infant’s immune system.
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Global and regional associations of enteric infections and asthma medRxiv. Allergy Immunol. Pub Date : 2024-05-21 Duan Ni, Ralph Nanan
Asthma is one of the most common chronic diseases globally. There are various risk factors for asthma, including respiratory infections, like rhinovirus and respiratory syncytial virus infections. Nevertheless, impacts from non-respiratory tract infections on asthma remain unresolved. Globally, enteric infections are the most common infections. Their target organ, the intestinal system, shares the
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Compound heterozygous mutations in the kinase domain of IKKα lead to immunodeficiency and immune dysregulation medRxiv. Allergy Immunol. Pub Date : 2024-05-17 Quentin Riller, Boris Sorin, Charline Courteille, Duong Ho-Nhat, Tom Le Voyer, Jean-Christophe Debray, Marie-Claude Stolzenberg, Olivier Pellé, Thomas Becquard, María Rodrigo Riestra, Laureline Berteloot, Mélanie Migaud, Laure Delage, Marie Jeanpierre, Charlotte Boussard, Camille Brunaud, Aude Magérus, Victor Michel, Camille Roux, Capucine Picard, Cécile Masson, Christine Bole-Feysot, Nicolas Cagnard
IKKα, encoded by CHUK, is crucial in the non-canonical NF-κB pathway and part of the IKK complex activating the canonical pathway alongside IKKβ. Absence of IKKα cause fetal encasement syndrome in human, fatal in utero, while an impaired IKKα-NIK interaction was reported in a single patient and cause combined immunodeficiency. Here, we describe compound heterozygous variants in the kinase domain of
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Analysis of Differentially expressed genes and Molecular pathways in Peanut Allergy Induced Dynamic Changes involved in Peanut-Specific Immune Responses: A Systematic and Bioinformatics Approach medRxiv. Allergy Immunol. Pub Date : 2024-05-13 Glory Simon Parmar, Manisha Gulati, Md Khoshnade Rabby, Ramchander Merugu, Satabdi Mohanty, Umme Kulsum, Dhanshree Gajanan Pujari, Swapnja Rohit More, Om Prakash, Priyanka Shrikant Bhore, Deepshikha Satish
Peanut allergy poses a significant global health concern, triggering hypersensitivity reactions upon exposure to peanuts. Understanding the molecular mechanisms governing peanut-specific immune responses is imperative for developing effective therapeutic approaches. This study aimed to investigate differentially expressed genes (DEGs) and associated molecular pathways implicated in peanut allergy-induced
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Single Cell Sequencing of Human Langerhans Cells Identifies Altered Gene Expression Profiles in Patients with Atopic Dermatitis medRxiv. Allergy Immunol. Pub Date : 2024-05-09 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
Atopic dermatitis (AD) is characterized by dysregulated T cell immunity and skin microbiome dysbiosis with predominance of Staphylococcus aureus (S. aureus). Emerging evidence suggests a role for S. aureus in exacerbating AD skin inflammation. We have previously shown that specific glycosylation of S. aureus cell wall structures amplifies skin inflammation through interaction with Langerhans cells
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Demonstration of a Decongestant Effect of “Coldamaris Akut” Compared to Saline Nasal Spray in Participants Suffering from Seasonal Allergic Rhinitis medRxiv. Allergy Immunol. Pub Date : 2024-05-04 Nicole Unger-Manhart, Martina Morokutti-Kurz, Petra Zieglmayer, Patrick Lemell, Markus Savli, René Zieglmayer, Hanna Dellago, Eva Prieschl-Grassauer
Purpose 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.
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The RESIST Senior Individuals Cohort: Design, participant characteristics and aims medRxiv. Allergy Immunol. Pub Date : 2024-05-03 LM Roesner, KM Gupta, V Kopfnagel, N van Unen, Y Kemmling, J Heise, S Castell, X Jiang, L Riemann, S Traidl, B Lange, KW Sühs, T Illig, T Strowig, Y Li, R Förster, J Huehn, TF Schulz, T Werfel, the RESIST SI Cohort Investigators
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
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Global associations of maternal hypertensive disorders and offspring allergic disease burden medRxiv. Allergy Immunol. Pub Date : 2024-05-01 Duan Ni, Ralph Nanan
Objectives 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.
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Antibody Responses to SARS-Cov-2 among Health Care Workers of a Tertiary Hospital in North-Eastern, Tanzania medRxiv. Allergy Immunol. Pub Date : 2024-04-12 Pendo M Ibrahim, Felix Anthony, Happiness Mshana, Kevin Rwegoshola, Hadija Semvua, Jaffu Chilongola
Background 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
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Hybrid humoral immune response of Pacific Islanders to BNT162b2 vaccination and Delta/Omicron infection: a cohort study medRxiv. Allergy Immunol. Pub Date : 2024-04-10 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
Background 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.
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How dietary landscapes impact food allergy medRxiv. Allergy Immunol. Pub Date : 2024-04-08 Duan Ni, Alistair Senior, Jian Tan, Laurence Macia, Ralph Nanan
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
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Systems vaccinology identifies clinical and immunological correlates of SARS-CoV-2 vaccine response in solid-organ transplant recipients medRxiv. Allergy Immunol. Pub Date : 2024-04-06 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
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
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Repeated vaccination with homologous influenza hemagglutinin broadens human antibody responses to unmatched flu viruses medRxiv. Allergy Immunol. Pub Date : 2024-03-29 Yixiang Deng, Melbourne Tang, Ted M. Ross, Aaron G. Schmidt, Arup K. Chakraborty, Daniel Lingwood
The on-going diversification of influenza virus necessicates annual vaccine updating. The vaccine antigen, the viral spike protein hemagglutinin (HA), tends to elicit strain-specific neutralizing activity, predicting that sequential immunization with the same HA strain will boost antibodies with narrow coverage. However, repeated vaccination with homologous SARS-CoV-2 vaccine eventually elicits neutralizing
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The extent and impact of vaccine status miscategorisation on covid-19 vaccine efficacy studies medRxiv. Allergy Immunol. Pub Date : 2024-03-25 Martin Neil, Scott McLachlan, Norman Fenton
It is recognised that many studies reporting high efficacy for Covid-19 vaccines suffer from various selection biases. Systematic review identified thirty-nine studies that suffered from one particular and serious form of bias called miscategorisation bias, whereby study participants who have been vaccinated are categorised as unvaccinated up to and until some arbitrarily defined time after vaccination
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Expanded T cell clones with lymphoma driver somatic mutations in refractory celiac disease medRxiv. Allergy Immunol. Pub Date : 2024-03-22 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
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
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Splice site and de novo mutations can cause mixed gain of function/dominant negative PLCG2-associated immune dysregulation with cold urticaria (CU-PLAID) medRxiv. Allergy Immunol. Pub Date : 2024-03-19 Sophia Renee Chou, Alexis Christine Bailey, Kathleen Christine Baysac, Andrew Oler, Joshua D. Milner, Michael Joseph Ombrello
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
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Specific long-term changes in anti-SARS-CoV-2 IgG modifications and antibody functions in mRNA, adenovector, and protein subunit vaccines medRxiv. Allergy Immunol. Pub Date : 2024-03-14 Sebastian Reinig, Chin Kuo, Chia-Chun Wu, Sheng-yu Huang, Jau-Song Yu, Shin-Ru Shih
Various vaccine platforms were developed and deployed against the COVID-19 disease. The Fc-mediated functions of IgG antibodies are essential in the adaptive immune response elicited by vaccines. However, the long-term changes of protein subunit vaccines and their combinations with mRNA vaccines are unknown. A total of 272 serum and plasma samples were collected from individuals who received first
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Clinical multi-omics reveals the role of Tuomin Zhiti Decoction Intervention in Allergic Rhinitis from the perspective of biological network medRxiv. Allergy Immunol. Pub Date : 2024-03-13 Weibo Zhao, Boyang Wang, Lingyao Kong, Qi Wang, Shao Li
Background: Increasing evidence showed that seasonal allergic rhinitis (SAR), as an allergy disease, could be alleviated with traditional Chinese medicine (TCM) formula, one example being Tuomin Zhiti Decoction (TZD). However, as a complex composition of TCM herbs, the mechanism of TZD in the treatment of SAR remain unclear. Purpose: Uncover the mechanism of TZD for treating SAR based on computational
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Integrating circulating T follicular memory cells and autoantibody repertoires for characterization of autoimmune disorders medRxiv. Allergy Immunol. Pub Date : 2024-03-07 Emily M. Harris, Sarah Chamseddine, Anne Chu, Leetah Senkpeil, Matthew Nikiciuk, Amer Al-Musa, Brian Woods, Elif Ozdogan, Sarife Saker, David P Hoytema van Konijnenburg, Christina S.K. Yee, Ryan Nelson, Pui Y Lee, Olha Halyabar, Rebecca C Hale, Megan Day-Lewis, Lauren A Henderson, Alan A Nguyen, Megan Elkins, Toshiro K. Ohsumi, Maria Gutierrez-Arcelus, Janique M. Peyper, Craig D. Platt, Rachael F.
Introduction. Autoimmune diseases are heterogeneous and often lack specific or sensitive diagnostic tests. Increased percentages of CD4+CXCR5+PD1+ circulating T follicular helper (cTfh) cells and skewed distributions of cTfh subtypes have been associated with autoimmunity. However, cTfh cell percentages can normalize with immunomodulatory treatment despite persistent disease activity, indicating the
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Longitudinal Analysis Over Decades Reveals the Development and Immune Implications of Type I Interferon Autoantibodies in an Aging Population medRxiv. Allergy Immunol. Pub Date : 2024-03-06 Sonja Fernbach, Nina K. Mair, Irene A. Abela, Kevin Groen, Roger Kuratli, Marie Lork, Christian W. Thorball, Enos Bernasconi, Paraskevas Filippidis, Karoline Leuzinger, Julia Notter, Andri Rauch, Hans H. Hirsch, Michael Huber, Huldrych F. Günthard, Jacques Fellay, Roger D. Kouyos, Benjamin G. Hale, The Swiss HIV Cohort Study
Pre-existing autoantibodies (autoAbs) neutralizing type I interferons (IFN-Is: IFNα, IFNβ, IFNω) have recently been described as significant contributors to the severity of viral infectious diseases. Here, we explore the development and consequences of anti-IFN-I autoAbs at high-resolution using retrospective samples and data from 1876 well-treated individuals >65 years of age enrolled in the Swiss
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The Majority of SARS-CoV-2 Plasma Cells are Excluded from the Bone Marrow Long-Lived Compartment 33 Months after mRNA Vaccination medRxiv. Allergy Immunol. Pub Date : 2024-03-05 Doan C Nguyen, Ian T Hentenaar, Andrea Morrison-Porter, David Solano, Natalie S. Haddad, Carlos Castrillon, Pedro A Lamothe, Joel Andrews, Danielle Roberts, Sagar Lonial, Ignacio Sanz, Frances Eun-Hyung Lee
The goal of any vaccine is to induce long-lived plasma cells (LLPC) to provide life-long protection. Natural infection by influenza, measles, or mumps viruses generates bone marrow (BM) LLPC similar to tetanus vaccination which affords safeguards for decades. Although the SARS-CoV-2 mRNA vaccines protect from severe disease, the serologic half-life is short-lived even though SARS-CoV-2-specific plasma