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Trained immunity-based vaccines for infections and allergic diseases. J. Allergy Clin. Immunol. (IF 11.4) Pub Date : 2024-09-18 Leticia Martín-Cruz,Cristina Benito-Villalvilla,Alba Angelina,José Luis Subiza,Oscar Palomares
Trained immunity has emerged as a new concept in immunology associated with the memory of innate immune cells and linked to specific metabolic and epigenetic reprogramming of these cells. Trained immunity may confer nonspecific and sustained protection against a broad range of pathogens, and recent findings show that it might also be involved in allergy mechanisms. Some conventional vaccines have demonstrated
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European Society of Immunodeficiencies guidelines for the management of patients with congenital athymia. J. Allergy Clin. Immunol. (IF 11.4) Pub Date : 2024-09-18 Alexandra Y Kreins,Fatima Dhalla,Aisling M Flinn,Evey Howley,Olov Ekwall,Anna Villa,Frank Jt Staal,Graham Anderson,Andrew R Gennery,Georg A Holländer,E Graham Davies,
Congenital athymia is a life-limiting disorder due to rare inborn errors of immunity causing impaired thymus organogenesis or abnormal thymic stromal cell development and function. Athymic infants have a T-B+NK+ immunophenotype with profound T lymphocyte deficiency and are susceptible to severe infections and autoimmunity. Patients variably display syndromic features. Expanding access to newborn screening
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Serum Cytokine Panels in Pediatric Clinical Practice. J. Allergy Clin. Immunol. (IF 11.4) Pub Date : 2024-09-18 Paul M Gallo,Jihwan Kim,Kevin O McNerney,Caroline Diorio,Caelin Foley,Laura Kagami,Kristina Wagner,Whitney L Petrosa,Hana Conlon,Kandace L Gollomp,Scott W Canna,Alix E Seif,Maire A Conrad,Judith R Kelsen,Neil Romberg,Hamid Bassiri,Kathleen E Sullivan,David T Teachey,Michele E Paessler,Edward M Behrens,Michele P Lambert
BACKGROUND Cytokines are soluble signaling proteins that regulate inflammation and coordinate immune responses. Serum cytokine assays are increasingly used in medical practice, yet our understanding of cytokines as biomarkers for disease remains limited. OBJECTIVES We aimed to analyze real-world single center usage of a multiplexed cytokine panel, correlate its results with diagnosis and severity,
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Determinants of Persistence and Recovery of Chronic COVID19 Chemosensory Dysfunction. J. Allergy Clin. Immunol. (IF 11.4) Pub Date : 2024-09-11 Dante G Minichetti,Amelia Boyd,Evan Lemire,Jonathan Hacker,Adam L Haber,Rachel E Roditi,Mark W Albers,Stella Lee,Kathleen M Buchheit,Tanya M Laidlaw,Lora G Bankova
BACKGROUND In 2-4% of patients, COVID19 chemosensory dysfunction (CSD) persists beyond six months, accounting for up to 4 million people in the US. The predictors of persistence and recovery require further exploration. OBJECTIVE To define the predictors of recovery and assess the quality of CSD in registry subjects with self-reported persistent smell and taste dysfunction after COVID19. METHODS COVID19
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Tissue-specific inducible IL-33 expression elicits features of eosinophilic esophagitis. J. Allergy Clin. Immunol. (IF 11.4) Pub Date : 2024-09-10 Grace C Pyon,Mia Y Masuda,Arina Putikova,Huijun Luo,Jessica B Gibson,Adelyn D Dao,Danna R Ortiz,Piper L Heiligenstein,James J Bonellos,William E LeSuer,Rish K Pai,Shipra Garg,Matthew A Rank,Hiroshi Nakagawa,Hirohito Kita,Benjamin L Wright,Alfred D Doyle
BACKGROUND IL-33 is a type 2 inflammatory cytokine that is elevated in the esophageal epithelium of EoE subjects. We previously developed a mouse model of EoE dependent on constitutive overexpression of IL-33 from the esophageal epithelium (EoE33). OBJECTIVE Our objective was to develop an inducible, IL-33-dependent model of EoE and examine induction of EoE-associated pathology. METHODS We utilized
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NETs activate Notch- γ secretase signaling in hidradenitis suppurativa. J. Allergy Clin. Immunol. (IF 11.4) Pub Date : 2024-09-10 Christopher B Oliveira,Jorge Romo-Tena,Eduardo Patino-Martinez,Alexandra Woo,Angel S Byrd,Dongwon Kim,Ginette A Okoye,Mariana J Kaplan,Carmelo Carmona-Rivera
BACKGROUND Hidradenitis suppurativa (HS) is an inflammatory chronic skin disorder of unknown etiology characterized by inflamed abscess-like nodules and boils resulting in sinus tract formation, tissue scarring and massive infiltration of neutrophils. Multiple lines of evidence have highlighted the potential association between alterations in the Notch pathway and HS pathogenesis, but the mechanisms
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From genes to geography: mapping allergic disease landscapes with spatial transcriptomics. J. Allergy Clin. Immunol. (IF 11.4) Pub Date : 2024-09-09 Sumanth Chennareddy,Patrick M Brunner
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Gain-of-Function Variants in SMAD4 Compromise Respiratory Epithelial Function. J. Allergy Clin. Immunol. (IF 11.4) Pub Date : 2024-09-05 Mark E Lindsay,Eleanor R Scimone,Joseph Lawton,Rashmi Richa,Lael M Yonker,Yuanpu P Di,Karen Buch,Wukun Ouyang,Xiulei Mo,Angela E Lin,Hongmei Mou
BACKGROUND Myhre syndrome (MIM #139210) is an exceedingly rare yet increasingly diagnosed genetic disorder arising from germline variants in the SMAD4 gene. Its core manifestation is the progression of stiffness and fibrosis across multiple organs. Individuals with Myhre syndrome exhibit a propensity for upper respiratory remodeling and infections. The molecular and cellular mechanisms underlying this
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Hematopoietic Cell Transplantation for DOCK8 Deficiency: Results from a Prospective Clinical Trial. J. Allergy Clin. Immunol. (IF 11.4) Pub Date : 2024-09-02 Alexandra F Freeman,Corina E Gonzalez,Bonnie Yates,Kristen Cole,Lauren Little,Erin Flannelly,Seth M Steinberg,George Mo,Nicole Piette,Thomas E Hughes,Jennifer Cuellar-Rodriguez,Juan Gea-Banacloche,Theo Heller,Dima A Hammoud,Steve M Holland,Heidi H Kong,Fernanda D Young,Huie Jing,Basak Kayaoglu,Helen C Su,Sung-Yun Pai,Dennis D Hickstein,Nirali N Shah
BACKGROUND Dedicator of cytokinesis 8 (DOCK8) deficiency is a primary immunodeficiency in which allogeneic hematopoietic cell transplantation (HCT) represents the only known cure. We tested the ability of a busulfan-based regimen to achieve reliable engraftment and high levels of donor chimerism with acceptable toxicity in a prospective clinical trial in DOCK8 deficiency. OBJECTIVE To both evaluate
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1-Food versus 4-Food Elimination Diet for Pediatric Eosinophilic Esophagitis: A Multi-site Randomized Trial. J. Allergy Clin. Immunol. (IF 11.4) Pub Date : 2024-09-02 Kara L Kliewer,J Pablo Abonia,Seema S Aceves,Dan Atkins,Peter A Bonis,Kelley E Capocelli,Mirna Chehade,Margaret H Collins,Evan S Dellon,Lin Fei,Glenn T Furuta,Sandeep K Gupta,Amir Kagalwalla,John Leung,Sabina Mir,Vincent A Mukkada,Robbie Pesek,Chen Rosenberg,Tetsuo Shoda,Jonathan M Spergel,Qin Sun,Joshua B Wechsler,Guang-Yu Yang,Marc E Rothenberg
BACKGROUND A 6-food elimination diet in pediatric eosinophilic esophagitis (EoE) is difficult to implement and may negatively impact quality of life (QoL). Less restrictive elimination diets may balance QoL and efficacy. OBJECTIVE We performed a multi-site, randomized comparative efficacy trial of a 1-food (milk) elimination diet (1FED) versus 4-food (milk, egg, wheat, soy) elimination diet (4FED)
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Haematopoietic stem cell transplantation for CTLA-4 insufficiency across Europe: an EBMT Inborn Errors Working Party study. J. Allergy Clin. Immunol. (IF 11.4) Pub Date : 2024-08-30 Christo Tsilifis,Carsten Speckmann,Su Han Lum,Thomas A Fox,Adriana Margarit Soler,Yasmina Mozo,Dolores Corral,Anna-Maria Ewins,Rosie Hague,Christina Oikonomopoulou,Krzysztof Kałwak,Katarzyna Drabko,Robert Wynn,Emma C Morris,Suzanne Elcombe,Venetia Bigley,Vassilios Lougaris,Michele Malagola,Fabian Hauck,Petr Sedlacek,Alexandra Laberko,Jennifer M L Tjon,Emilie P Buddingh,Claudia Wehr,Bodo Grimbacher
BACKGROUND Cytotoxic T-lymphocyte antigen-4 (CTLA-4) insufficiency causes a primary immune regulatory disorder characterised by lymphoproliferation, dysgammaglobulinaemia, and multi-organ autoimmunity including cytopenias and colitis. OBJECTIVE To examine the outcome of HSCT for CTLA-4 insufficiency and study the impact of pre-HSCT CTLA-4-Ig therapy and pre-HSCT immune dysregulation on survival and
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Subcutaneous immunotherapy for bee venom allergy induces epitope spreading and immunophenotypic changes in allergen-specific memory B cells. J. Allergy Clin. Immunol. (IF 11.4) Pub Date : 2024-08-30 Craig I McKenzie,Simone Reinwald,Brett Averso,Brett Spurrier,Andrew Satz,Anouk von Borstel,Sabina Masinovic,Nirupama Varese,Pei Mun Aui,Bruce D Wines,P Mark Hogarth,Mark Hew,Jennifer M Rolland,Robyn E O'Hehir,Menno C van Zelm
BACKGROUND Allergen immunotherapy (AIT) is the only disease-modifying treatment for allergic disorders. We have recently discovered that allergen-specific memory B-cells (Bmem) are phenotypically altered after 4 months sublingual AIT for ryegrass pollen allergy. Whether these effects are shared with subcutaneous AIT (SCIT) and affect the epitope-specificity of Bmem remain unknown. OBJECTIVE To evaluate
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Deep Multi-Omic Profiling Reveals Molecular Signatures that Underpin Preschool Wheeze and Asthma. J. Allergy Clin. Immunol. (IF 11.4) Pub Date : 2024-08-28 Matthew Macowan,Céline Pattaroni,Katie Bonner,Roxanne Chatzis,Carmel Daunt,Mindy Gore,Adnan Custovic,Michael D Shields,Ultan F Power,Jonathan Grigg,Graham Roberts,Peter Ghazal,Jürgen Schwarze,Steve Turner,Andrew Bush,Sejal Saglani,Clare M Lloyd,Benjamin J Marsland
BACKGROUND Wheezing in childhood is prevalent, with over half of all children experiencing at least one episode by age six. The pathophysiology of wheeze, especially why some children develop asthma while others do not, remains unclear. OBJECTIVE This study addresses the knowledge gap by investigating the transition from preschool wheeze to asthma using multi-omic profiling. METHODS Unsupervised, group-agnostic
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Metabolic dysfunction mediated by HIF-1α contributes to epithelial differentiation defects in eosinophilic esophagitis. J. Allergy Clin. Immunol. (IF 11.4) Pub Date : 2024-08-27 Sinéad Ryan,Louise Crowe,Sofía N Almeida Cruz,Matthew D Galbraith,Carol O'Brien,Juliet A Hammer,Ronan Bergin,Shauna K Kellett,Gary E Markey,Taylor M Benson,Olga Fagan,Joaquin M Espinosa,Niall Conlon,Claire L Donohoe,Susan McKiernan,Andrew E Hogan,Eóin N McNamee,Glenn T Furuta,Calies Menard-Katcher,Joanne C Masterson
BACKGROUND Investigating the contributory role that epithelial cell metabolism plays in allergic inflammation is a key factor to understanding what influences dysfunction and the pathogenesis of the allergic disease eosinophilic esophagitis (EoE). We previously highlighted that the absence of hypoxia signaling through hypoxia-inducible factor (HIF)-1α in EoE contributes to esophageal epithelial dysfunction
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The processed milk hypothesis: A major factor in the development of eosinophilic esophagitis (EoE)? J. Allergy Clin. Immunol. (IF 11.4) Pub Date : 2024-08-26 James R Baker,Roopesh Singh Gangwar,Thomas A Platts-Mills
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Comparative Effectiveness of Dupilumab and Omalizumab on Asthma Exacerbations and Systemic Corticosteroid Prescriptions: Real-World US ADVANTAGE Study. J. Allergy Clin. Immunol. (IF 11.4) Pub Date : 2024-08-24 Eugene Bleecker,Michael Blaiss,Juby Jacob-Nara,Lynn Huynh,Mei Sheng Duh,Tracy Guo,Mingchen Ye,Richard H Stanford,Zhixiao Wang,Xavier Soler,Arpita Nag,Radhika Nair,Kinga Borsos
BACKGROUND In the US, dupilumab is approved for moderate-to-severe eosinophilic or oral corticosteroid-dependent asthma, while omalizumab is approved for managing moderate-to-severe allergic asthma uncontrolled by inhaled corticosteroids. However, limited comparative effectiveness data exist for these biologics due to differing patient characteristics and treatment histories. OBJECTIVE This analysis
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Evolving spectrum of adenosine deaminase (ADA) deficiency: Assessing genotype pathogenicity according to expressed ADA activity of 46 variants. J. Allergy Clin. Immunol. (IF 11.4) Pub Date : 2024-08-23 Ines Santisteban,Francisco X Arredondo-Vega,Pawan Bali,Busra Dalgic,Hyun Ho Lee,Minsoo Kim,Jake Hermanson,Teresa K Tarrant,Michael S Hershfield
BACKGROUND Deficiency of adenosine deaminase (ADA or ADA1) has broad clinical and genetic heterogeneity. Screening techniques can identify asymptomatic infants whose phenotype and prognosis are indeterminate, and who may carry ADA variants of unknown significance. OBJECTIVE We systematically assessed the pathogenic potential of rare ADA missense variants to better define the relationship of genotype
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Indoor Air Pollution and Airway Health. J. Allergy Clin. Immunol. (IF 11.4) Pub Date : 2024-08-23 Jared Radbel,Meghan E Rebuli,Howard Kipen,Emily Brigham
Due to the disproportionate amount of time people spend indoors, and the complexities of air pollutant exposures found there, indoor air pollution is a growing concern for airway health. Both infiltration of outdoor air pollution into the indoor space, and indoor sources (such as smoke from tobacco products, cooking or heating practices and combustion of associated fuels, household materials) contribute
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Cleaning Indoor Air- What Works for Respiratory Health: An Updated Literature Review and Recommendations. J. Allergy Clin. Immunol. (IF 11.4) Pub Date : 2024-08-22 Nicole M Robertson,Anna Qiu,Sarath Raju,Meredith C McCormack,Kirsten Koehler
Indoor air pollution is a growing public health concern globally and is associated with increased respiratory symptoms and morbidity. Individuals spend most of their time indoors, and pollutant-related health effects are often driven by the indoor environment. Understanding effective interventions to improve indoor air quality (IAQ) and their impact on respiratory outcomes is key to decreasing the
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Dupilumab reduces inflammatory biomarkers in pediatric patients with moderate-to-severe atopic dermatitis. J. Allergy Clin. Immunol. (IF 11.4) Pub Date : 2024-08-21 Lisa A Beck,Antonella Muraro,Mark Boguniewicz,Zhen Chen,Joseph Zahn,Ainara Rodríguez Marco
BACKGROUND Patients with atopic dermatitis (AD) often have elevated type 2 inflammatory serum biomarkers. OBJECTIVE To report changes in thymus- and activation-regulated chemokine (TARC)/CC chemokine ligand 17 (CCL17), total immunoglobulin E (IgE), lactate dehydrogenase (LDH), and eosinophils in pediatric patients treated with dupilumab or placebo. METHODS Biomarker data were analyzed from three randomized
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Effects of pregnancy and lactation prebiotics supplementation on infant allergic disease: A randomized controlled trial. J. Allergy Clin. Immunol. (IF 11.4) Pub Date : 2024-08-21 Debra J Palmer,Alana R Cuthbert,Thomas R Sullivan,Rachelle A Pretorius,Johan Garssen,Kristina Rueter,Maria C Jenmalm,Jeffrey A Keelan,Desiree Silva,Susan L Prescott
BACKGROUND Ingestion of prebiotics during pregnancy and lactation may have immunomodulatory benefits for the developing fetal and infant immune system and provide a potential dietary strategy to reduce the risk of allergic diseases. OBJECTIVE We sought to determine whether maternal supplementation with dietary prebiotics reduces the risk of allergic outcomes in infants with hereditary risk. METHODS
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Increasing Awareness Regarding the Relationship between Environmental Exposures and Allergic Disease. J. Allergy Clin. Immunol. (IF 11.4) Pub Date : 2024-08-20 Ellen R Conroy,Rachel Peterson,Wanda Phipatanakul,William J Sheehan
This review highlights studies from the past 3 years that add to the understanding of the impact of environmental exposures on allergic disease. These include aeroallergens, air quality, prenatal or early life exposures, and occupational exposures. Recent studies focused on the relationship between the environment, the microbiome, and allergic disease as well as new therapeutic options are also reviewed
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Indoor allergen exposure and its association to upper respiratory infections and pulmonary outcomes among children with asthma. J. Allergy Clin. Immunol. (IF 11.4) Pub Date : 2024-08-19 Darlene Bhavnani,Travis Lilley,Paul J Rathouz,Sylvie Beaudenon-Huibregtse,Meghan F Davis,Meredith C McCormack,Corinne A Keet,Susan Balcer-Whaley,Michelle Newman,Elizabeth C Matsui
BACKGROUND Certain environmental allergen exposures are more common in disadvantaged communities and may contribute to differences in susceptibility to upper respiratory infections (URIs). OBJECTIVES We examined associations between indoor allergens and: (1) URI; (2) URI + cold symptoms; (3) URI + cold symptoms + pulmonary eosinophilic inflammation (fraction of exhaled nitric oxide ≥20 ppb); and (4)
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Applying the dissemination and implementation sciences to allergy and immunology: A Work Group Report from the AAAAI Quality, Adherence, and Outcomes Committee. J. Allergy Clin. Immunol. (IF 11.4) Pub Date : 2024-08-19 Sujani Kakumanu,Stanley Szefler,Andrea A Pappalardo,Anne E Sales,Alan P Baptist,Jessica Stern,Sharmilee M Nyenhuis
Translating evidence-based practice (EBP) into real-world clinical settings often takes a considerable amount of time and resources. In allergy and immunology, the dissemination and implementation (D&I) sciences facilitate the study of how variations in knowledge, resources, patient populations, and staffing models lead to differences in the clinical care of asthma, allergic disease, and primary immunodeficiency
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Utility of epitope-specific IgE, IgG4, and IgG1 antibodies for the diagnosis of wheat allergy. J. Allergy Clin. Immunol. (IF 11.4) Pub Date : 2024-08-21 Witchaya Srisuwatchari,Mayte Suárez-Fariñas,Andrew D Delgado,Galina Grishina,Maria Suprun,Ashley Sang Eun Lee,Pakit Vichyanond,Punchama Pacharn,Hugh A Sampson
BACKGROUND The bead-based epitope assay has been used to identify epitope-specific (es) antibodies and successfully used to diagnose clinical allergy to milk, egg, and peanut. OBJECTIVE We sought to identify es-IgE, es-IgG4, and es-IgG1 of wheat proteins and determine the optimal peptides to differentiate wheat-allergic from wheat-tolerant using the bead-based epitope assay. METHODS Children and adolescents
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Interactions between eosinophils and IL-5Rα-positive mast cells in nonadvanced systemic mastocytosis. J. Allergy Clin. Immunol. (IF 11.4) Pub Date : 2024-08-14 Guillaume Lefèvre,Jean-Baptiste Gibier,Antonino Bongiovanni,Ludovic Lhermitte,Julien Rossignol,Emilie Anglo,Arnaud Dendooven,Romain Dubois,Louis Terriou,David Launay,Stéphane Barete,Stéphane Esnault,Laurent Frenzel,Clément Gourguechon,Thomas Ballul,Frédéric Dezoteux,Delphine Staumont-Salle,Marie-Christine Copin,Rachel Rignault-Bricard,Thiago Trovati Maciel,Gandhi Damaj,Meryem Tardivel,Marie Crinquette-Verhasselt
BACKGROUND Bidirectional interactions between eosinophils and mast cells (MCs) have been reported in various allergic diseases. Bone marrow (BM) eosinophilia, and to a lesser extent blood eosinophilia, is common in systemic mastocytosis (SM), but its significance remains unknown. OBJECTIVE We described blood and BM eosinophil characteristics in SM. METHODS A large collection of BM biopsy samples was
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The clinical, mechanistic, and social impacts of air pollution on atopic dermatitis. J. Allergy Clin. Immunol. (IF 11.4) Pub Date : 2024-08-14 Jordan Zeldin,Grace Ratley,Nadia Shobnam,Ian A Myles
Atopic dermatitis (AD) is a complex disease characterized by dry, pruritic skin and significant atopic and psychological sequelae. Although AD has always been viewed as multifactorial, early research was dominated by overlapping genetic determinist views of either innate barrier defects leading to inflammation or innate inflammation eroding skin barrier function. Since 1970, however, the incidence
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Dupilumab response onset, maintenance, and durability in patients with severe CRSwNP. J. Allergy Clin. Immunol. (IF 11.4) Pub Date : 2024-08-14 Claus Bachert,Asif H Khan,Wytske J Fokkens,Claire Hopkins,Philippe Gevaert,Joseph K Han,Peter W Hellings,Stella E Lee,Jérôme Msihid,Scott Nash,Harry Sacks,Juby A Jacob-Nara,Yamo Deniz,Paul J Rowe
BACKGROUND Responder analyses of SINUS phase 3 study data have shown clinically meaningful improvements across multiple outcomes of treatment of chronic rhinosinusitis with nasal polyps (CRSwNP) with dupilumab. OBJECTIVE Our aim was to gain a better understanding of dynamics of the response to dupilumab over 52 weeks. METHODS We used data from the SINUS-52 (ClinicalTrials.gov identifier NCT02898454)
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IL-2 family cytokines IL-9 and IL-21 differentially regulate innate and adaptive type 2 immunity in asthma. J. Allergy Clin. Immunol. (IF 11.4) Pub Date : 2024-08-13 Fabian Bick,Claudia M Brenis Gómez,Inés Lammens,Justine Van Moorleghem,Caroline De Wolf,Sam Dupont,Laure Dumoutier,Neal P Smith,Alexandra-Chloé Villani,Robin Browaeys,Jehan Alladina,Alexis M Haring,Benjamin D Medoff,Josalyn L Cho,René Bigirimana,Joao Vieira,Hamida Hammad,Christophe Blanchetot,Martijn J Schuijs,Bart N Lambrecht
BACKGROUND Asthma is often accompanied by type 2 immunity rich in IL-4, IL-5, and IL-13 cytokines produced by TH2 lymphocytes or type 2 innate lymphoid cells (ILC2s). IL-2 family cytokines play a key role in the differentiation, homeostasis, and effector function of innate and adaptive lymphocytes. OBJECTIVE IL-9 and IL-21 boost activation and proliferation of TH2 and ILC2s, but the relative importance
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Variants in IGLL1 cause a broad phenotype from agammaglobulinemia to transient hypogammaglobulinemia. J. Allergy Clin. Immunol. (IF 11.4) Pub Date : 2024-08-13 Maarja Soomann,Viktor Bily,Magdeldin Elgizouli,Dennis Kraemer,Gülfirde Akgül,Horst von Bernuth,Markéta Bloomfield,Nicholas Brodszki,Fabio Candotti,Elisabeth Förster-Waldl,Tomas Freiberger,Maria Giżewska,Adam Klocperk,Uwe Kölsch,Kim E Nichols,Renate Krüger,Ninad Oak,Małgorzata Pac,Seraina Prader,Kjeld Schmiegelow,Anna Šedivá,Georgios Sogkas,Anna Stittrich,Ulrik Kristoffer Stoltze,Katerina Theodoropoulou
BACKGROUND Agammaglobulinemia due to variants in IGLL1 has traditionally been considered an exceedingly rare form of severe B-cell deficiency, with only 8 documented cases in the literature. Surprisingly, the first agammaglobulinemic patient identified by newborn screening (NBS) through quantification of kappa-deleting recombination excision circles harbored variants in IGLL1. OBJECTIVE We comprehensively
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Skin microdialysis detects distinct immunologic patterns in chronic inflammatory skin diseases. J. Allergy Clin. Immunol. (IF 11.4) Pub Date : 2024-08-12 Moritz Maximilian Hollstein,Stephan Traidl,Anne Heetfeld,Susann Forkel,Andreas Leha,Natalia Alkon,Jannik Ruwisch,Christof Lenz,Michael Peter Schön,Martin Schmelz,Patrick Brunner,Martin Steinhoff,Timo Buhl
BACKGROUND Insight into the pathophysiology of inflammatory skin diseases, especially at the proteomic level, is severely hampered by the lack of adequate in situ data. OBJECTIVE We characterized lesional and nonlesional skin of inflammatory skin diseases using skin microdialysis. METHODS Skin microdialysis samples from patients with atopic dermatitis (AD, n = 6), psoriasis vulgaris (PSO, n = 7), or
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Microbial intestinal dysbiosis drives long-term allergic susceptibility by sculpting an ILC2-B1 cell-innate IgE axis. J. Allergy Clin. Immunol. (IF 11.4) Pub Date : 2024-08-10 Ahmed Kabil,Natalia Nayyar,Julyanne Brassard,Yicong Li,Sameeksha Chopra,Michael R Hughes,Kelly M McNagny
BACKGROUND The abundance and diversity of intestinal commensal bacteria influence systemic immunity with impact on disease susceptibility and severity. For example, loss of short chain fatty acid (SCFA)-fermenting bacteria in early life (humans and mice) is associated with enhanced type 2 immune responses in peripheral tissues including the lung. OBJECTIVE Our goal was to reveal the microbiome-dependent
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Race and ethnicity, not just insurance, is associated with biologics initiation in asthma and related conditions. J. Allergy Clin. Immunol. (IF 11.4) Pub Date : 2024-08-06 Ayobami Akenroye,Christopher Hvisdas,Jessica Stern,John W Jackson,Margee Louisias
BACKGROUND There are pre-existing inequities in asthma care. OBJECTIVES We sought to evaluate effect modification by race of the effect of insurance on biologic therapy use in patients with asthma and related diseases. METHODS We conducted inverse probability weighted analyses using electronic health records data from 2011 to 2020 from a large health care system in Boston, Mass. We evaluated the odds
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Advances and ongoing challenges in eosinophilic gastrointestinal disorders presented at the CEGIR/TIGERs Symposium at the 2024 American Academy of Allergy, Asthma & Immunology meeting. J. Allergy Clin. Immunol. (IF 11.4) Pub Date : 2024-08-05 Benjamin L Wright,Juan Pablo Abonia,Edsel M Abud,Seema S Aceves,Steven J Ackerman,Melinda Braskett,Joy W Chang,Mirna Chehade,Gregory M Constantine,Carla M Davis,Evan S Dellon,Alfred D Doyle,Raquel Durban,David A Hill,Elizabeth T Jensen,Anupama Kewalramani,Paneez Khoury,Amy D Klion,Leah Kottyan,Fei Li Kuang,Emily C McGowan,Melanie A Ruffner,Lisa A Spencer,Jonathan M Spergel,Amiko M Uchida,Joshua B Wechsler
The Consortium of Eosinophilic Gastrointestinal disease Researchers (CEGIR) and The International Gastrointestinal Eosinophil Researchers (TIGERs) organized a daylong symposium at the 2024 annual meeting of the American Academy of Allergy, Asthma & Immunology. The symposium featured new discoveries in basic and translational research as well as debates on the mechanisms and management of eosinophilic
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Spatial transcriptomics reveals organized and distinct immune activation in cutaneous granulomatous disorders. J. Allergy Clin. Immunol. (IF 11.4) Pub Date : 2024-08-03 Joseph Daccache,Eunsuh Park,Muhammad Junejo,Mariam Abdelghaffar,Erica Hwang,Chitrasen Mohanty,Chandra K Singh,Guilin Wang,John O Wheeler,Bridget E Shields,Caroline A Nelson,Yiwei Wang,William Damsky
BACKGROUND Noninfectious (inflammatory) cutaneous granulomatous disorders include cutaneous sarcoidosis (CS), granuloma annulare (GA), necrobiosis lipoidica (NL), and necrobiotic xanthogranuloma (NXG). These disorders share macrophage-predominant inflammation histologically, but the inflammatory architecture and the pattern of extracellular matrix alteration varies. The underlying molecular explanations
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Airway proteomics reveals broad residual anti-inflammatory effects of prednisolone in mepolizumab-treated asthma. J. Allergy Clin. Immunol. (IF 11.4) Pub Date : 2024-08-02 Imran Howell,Freda Yang,Vanessa Brown,Jennifer Cane,Emanuele Marchi,Adnan Azim,John Busby,Pamela J McDowell,Sarah E Diver,Catherine Borg,Liam G Heaney,Ian D Pavord,Christopher E Brightling,Rekha Chaudhuri,Timothy S C Hinks
BACKGROUND Mepolizumab is an anti-IL-5 mAb treatment for severe eosinophilic asthma that reduces asthma exacerbations. Residual airway inflammation with mepolizumab therapy may lead to persistent exacerbations. Oral corticosteroids remain the main treatment for these residual exacerbations. OBJECTIVE Our study aimed to explore the corticosteroid responsiveness of airway inflammation after mepolizumab
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Comparative safety of oral Janus kinase inhibitors and dupilumab in patients with atopic dermatitis: a population-based cohort study. J. Allergy Clin. Immunol. (IF 11.4) Pub Date : 2024-08-01 Serena Yun-Chen Tsai,Wanda Phipatanakul,Elena B Hawryluk,Michiko K Oyoshi,Lynda C Schneider,Kevin Sheng-Kai Ma
BACKGROUND Systemic Janus kinase inhibitors (JAKi) and dupilumab both have emerged as promising therapeutics for atopic dermatitis (AD). While dupilumab has a favorable safety profile, use of oral JAKi has been established in other diseases that carry potential comorbid susceptibilities that influence safety. OBJECTIVE To provide real-world evidence of the safety of oral JAKi in AD patients. METHODS
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Disease heterogeneity and molecular classification of inflammatory palmoplantar diseases. J. Allergy Clin. Immunol. (IF 11.4) Pub Date : 2024-07-30 Kelsey R van Straalen,Joseph Kirma,Christine M Yee,Luke F Bugada,Syed M Rizvi,Fei Wen,Rachael Wasikowski,Jennifer Fox,Tran H Do,Charles F Schuler,Enze Xing,Amanda S MacLeod,Paul W Harms,Celine C Berthier,J Michelle Kahlenberg,Monica W L Leung,Lam C Tsoi,Johann E Gudjonsson
BACKGROUND Palmoplantar pustulosis (PPP) is an inflammatory disease characterized by relapsing eruptions of neutrophil-filled, sterile pustules on the palms and soles that can be clinically difficult to differentiate from non-pustular palmoplantar psoriasis (palmPP) and dyshidrotic palmoplantar eczema (DPE). OBJECTIVE We sought to identify overlapping and unique PPP, palmPP, and DPE drivers to provide
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TH2 cell compensatory effect following benralizumab treatment for eosinophilic gastritis. J. Allergy Clin. Immunol. (IF 11.4) Pub Date : 2024-07-30 Netali Ben-Baruch Morgenstern,Yrina Rochman,Julie M Caldwell,Margaret H Collins,Vincent A Mukkada,Philip E Putnam,Scott M Bolton,Kara L Kliewer,Marc E Rothenberg
BACKGROUND Eosinophil accumulation is a main feature of eosinophilic gastritis (EoG) and is associated with its histologic diagnosis and pathology. However, a recent clinical trial has demonstrated that EoG endoscopic, noneosinophil histologic, and clinical features remain persistent despite complete eosinophil depletion. OBJECTIVE Our aim was to examine gastric T-cell composition and associated cytokine
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Nonspecific lipid-transfer proteins trigger TLR2 and NOD2 signaling and undergo ligand-dependent endocytosis in epithelial cells. J. Allergy Clin. Immunol. (IF 11.4) Pub Date : 2024-07-29 Nicola Cavallari,Alexander Johnson,Christoph Nagl,Saskia Seiser,Gerald N Rechberger,Thomas Züllig,Thomas A Kufer,Adelheid Elbe-Bürger,Sabine Geiselhart,Karin Hoffmann-Sommergruber
BACKGROUND Allergens can cross the epithelial barrier to enter the body but how this cellular passage affects protein structures and the downstream interactions with the immune system are still open questions. OBJECTIVE We sought to show the molecular details and the effects of 3 nonspecific lipid transfer proteins (nsLTPs; Mal d 3 [allergenic nsLTP1 from apple], Cor a 8 [allergenic nsLTP1 from hazelnut]
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Preclinical efficacy of peanut-specific IgG4 antibody therapeutic IGNX001. J. Allergy Clin. Immunol. (IF 11.4) Pub Date : 2024-07-26 Derek Croote,Joyce J W Wong,Paige Creeks,Venu Aruva,Jeffrey J Landers,Matthew Kwok,Zainab Jama,Robert G Hamilton,Alexandra F Santos,Jessica J O'Konek,Roger Ferrini,G Roger Thomas,Henry B Lowman
BACKGROUND Existing therapeutic strategies are challenged by long times to achieve effect and often require frequent administration. Peanut-allergic individuals would benefit from a therapeutic that provides rapid protection against accidental exposure within days of administration while carrying little risk of adverse reactions. OBJECTIVE Guided by the repertoire of human IgE mAbs from allergic individuals
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Multiomics analysis identified IL-4-induced IL1RL1high eosinophils characterized by prominent cysteinyl leukotriene metabolism. J. Allergy Clin. Immunol. (IF 11.4) Pub Date : 2024-07-25 Keeya Sunata,Jun Miyata,Yusuke Kawashima,Ryo Konno,Masaki Ishikawa,Yoshinori Hasegawa,Ryuta Onozato,Yo Otsu,Emiko Matsuyama,Hisashi Sasaki,Shinichi Okuzumi,Takao Mochimaru,Katsunori Masaki,Hiroki Kabata,Akihiko Kawana,Makoto Arita,Koichi Fukunaga
BACKGROUND Clinical studies have demonstrated that IL-4, a type 2 cytokine, plays an important role in the pathogenesis of chronic rhinosinusitis and eosinophilic asthma. However, the direct effect of IL-4 on eosinophils remains unclear. OBJECTIVE We aimed to elucidate the inflammatory effects of IL-4 on the functions of human eosinophils. METHODS A multiomics analysis comprising transcriptomics, proteomics
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Mast cell-sensory neuron interactions under stress. J. Allergy Clin. Immunol. (IF 11.4) Pub Date : 2024-07-25 Theoharis C Theoharides
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Long-term durability between parent and child patient-reported outcomes in eosinophilic esophagitis. J. Allergy Clin. Immunol. (IF 11.4) Pub Date : 2024-07-25 Lisa J Martin,Xue Zhang,Mirna Chehade,Carla M Davis,Evan S Dellon,Gary W Falk,Sandeep K Gupta,Ikuo Hirano,Girish S Hiremath,David A Katzka,Paneez Khoury,John Leung,Paul Menard-Katcher,Nirmala Gonsalves,Robert D Pesek,Jonathan M Spergel,Joshua B Wechsler,Kara Kliewer,Nicoleta C Arva,Margaret H Collins,Maria Pletneva,Guang-Yu Yang,Glenn T Furuta,Marc E Rothenberg,Seema S Aceves
BACKGROUND Because young children cannot self-report symptoms, there is a need for parent surrogate reports. Although early work suggested parent-child alignment for eosinophil esophagitis (EoE) patient-reported outcomes (PROs), the longitudinal alignment is unclear. OBJECTIVE We sought to assess the agreement and longitudinal stability of PROs between children with EoE and their parents. METHODS A
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Circulating innate lymphoid cells (cILCs): Unconventional lymphocytes with hidden talents. J. Allergy Clin. Immunol. (IF 11.4) Pub Date : 2024-07-23 Sabrina B Bennstein,Markus Uhrberg
Innate lymphoid cells (ILCs) are a group of lymphocytes that are devoid of antigen-specific receptors and are mainly found in tissues. The subtypes ILC1, 2, and 3 mirror T-cell functionality in terms of cytokine production and expression of key transcription factors. Although the majority of ILCs are found in tissue (tILCs), they have also been described within the circulation (cILCs). As a result
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Mast cell β1 integrin localizes mast cells in close proximity to blood vessels and enhances their rapid responsiveness to intravenous antigen. J. Allergy Clin. Immunol. (IF 11.4) Pub Date : 2024-07-20 Stephen J Galli
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Dupilumab treatment decreases MBC2s, correlating with reduced IgE levels in pediatric atopic dermatitis. J. Allergy Clin. Immunol. (IF 11.4) Pub Date : 2024-07-20 Margot E Starrenburg,Manal Bel Imam,Juan F Lopez,Laura Buergi,N Tan Nguyen,Anouk E M Nouwen,Nicolette J T Arends,Peter J Caspers,Mübeccel Akdis,Suzanne G M A Pasmans,Willem van de Veen
BACKGROUND A preference for type 2 immunity plays a central role in the pathogenesis of atopic dermatitis (AD). Dupilumab, an mAb targeting the IL-4 receptor α (IL-4Rα) subunit, inhibits IL-4 and IL-13 signaling. These cytokines contribute significantly to IgE class switch recombination in B cells, critical in atopic diseases. Recent studies indicate IgG+CD23hiIL-4Rα+ type 2 memory B cells (MBC2s)
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An in vitro study of the impact of IL-17A and IL-22 on ciliogenesis in nasal polyps epithelium via the Hippo-YAP pathway. J. Allergy Clin. Immunol. (IF 11.4) Pub Date : 2024-07-20 Huijun Qiu,Jing Liu,Qingwu Wu,Hsiaohui Ong,Yana Zhang,Xuekun Huang,Tian Yuan,Rui Zheng,Huiyi Deng,Weihao Wang,Weifeng Kong,Xinyue Wang,Deyun Wang,Qintai Yang
BACKGROUND Cilia loss and impaired motile ciliary functions are among the typical pathological features of chronic rhinosinusitis with nasal polyps (CRSwNP). IL17A and IL22 are the canonical cytokines of type 3 inflammation, exhibiting similar functional effects on epithelial cells. In this study, we sought to examine the effects of IL17A and IL22 on ciliated cells and investigate the potential involvement
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Allergic fungal rhinosinusitis linked to other hyper-IgE syndromes through defective TH17 responses. J. Allergy Clin. Immunol. (IF 11.4) Pub Date : 2024-07-18 Hua Sun,J Morgan Knight,Yi-Dong Li,Faramarz Ashoori,Martin J Citardi,William C Yao,David B Corry,Amber U Luong
BACKGROUND In a gene expression analysis comparing sinus mucosa samples from allergic fungal rhinosinusitis (AFRS) patients with samples from non-AFRS chronic rhinosinusitis with nasal polyp (CRSwNP) patients, the antimicrobial peptide (AMP) histatin 1 (HTN1) was found to be the most differentially downregulated gene in AFRS. OBJECTIVE We sought to identify the molecular etiology of the downregulated
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Implementing a clinical decision support tool to increase early peanut introduction guidance. J. Allergy Clin. Immunol. (IF 11.4) Pub Date : 2024-07-10 Annabelle F Rowland,Thinh H Nguyen,Priscila P Cunha,Idil Ezhuthachan,Evan Orenstein,Swaminathan Kandaswamy,Tricia Lee
BACKGROUND General pediatric providers are the front line for early peanut introduction discussions, but many providers believe that they are ill-equipped to handle such discussions, as the guidelines have changed quickly. OBJECTIVE We hypothesized that a clinical decision support (CDS) tool could improve discussions of peanut introduction. METHODS CDS tools were designed by stakeholders, improved
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Sputum eosinophil peroxidase: Building a better biomarker for eosinophilic asthma. J. Allergy Clin. Immunol. (IF 11.4) Pub Date : 2024-07-10 Steven J Ackerman
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IL-4 acts on skin-derived dendritic cells to promote the TH2 response to cutaneous sensitization and the development of allergic skin inflammation. J. Allergy Clin. Immunol. (IF 11.4) Pub Date : 2024-07-10 Juan Manuel Leyva-Castillo,Mrinmoy Das,Maria Strakosha,Alex McGurk,Emilie Artru,Christy Kam,Mohammed Alasharee,Duane R Wesemann,Michio Tomura,Hajime Karasuyama,Frank Brombacher,Raif S Geha
BACKGROUND Atopic dermatitis is characterized by scratching and a TH2-dominated local and systemic response to cutaneously encountered antigens. Dendritic cells (DCs) capture antigens in the skin and rapidly migrate to draining lymph nodes (dLNs) where they drive the differentiation of antigen-specific naive T cells. OBJECTIVE We sought to determine whether non-T-cell-derived IL-4 acts on skin-derived
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Nonsense CD247 mutations show dominant-negative features in T-cell receptor expression and function. J. Allergy Clin. Immunol. (IF 11.4) Pub Date : 2024-07-09 Alejandro C Briones,Rebeca F Megino,Ana V Marin,Daniel Chacón-Arguedas,Elena García-Martinez,Héctor Balastegui-Martín,Hugh T Reyburn,Sarah E Henrickson,Carmen Rodríguez-Sainz,Elena Seoane-Reula,Paloma Sanchez-Mateos,Paula P Cardenas,Jose R Regueiro
BACKGROUND The invariant TCR ζ/CD247 homodimer is crucial for TCR/CD3 expression and signaling through its 3 immunoreceptor tyrosine-based activation motifs (ITAMs). Homozygous null mutations in CD247 lead to immunodeficiency, while carriers exhibit 50% reduced surface CD3. It is unclear whether carriers of other CD247 variants show dominant-negative effects. OBJECTIVE We sought to analyze and model
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Home and school pollutant exposure, respiratory outcomes, and influence of historical redlining. J. Allergy Clin. Immunol. (IF 11.4) Pub Date : 2024-07-09 Kyung Hwa Jung,Kira L Argenio,Daniel J Jackson,Rachel L Miller,Matthew S Perzanowski,Andrew G Rundle,Leonard B Bacharier,William W Busse,Robyn T Cohen,Cynthia M Visness,Michelle A Gill,Rebecca S Gruchalla,Gurjit K Hershey,Rachel K Kado,Michael G Sherenian,Andrew H Liu,Melanie M Makhija,Dinesh K Pillai,Katherine Rivera-Spoljaric,Peter J Gergen,Matthew C Altman,Megan T Sandel,Christine A Sorkness,Meyer
BACKGROUND The discriminatory and racist policy of historical redlining in the United States during the 1930s played a role in perpetuating contemporary environmental health disparities. OBJECTIVE Our objectives were to determine associations between home and school pollutant exposure (fine particulate matter [PM2.5], NO2) and respiratory outcomes (Composite Asthma Severity Index, lung function) among
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Human DNA-dependent protein kinase catalytic subunit deficiency: A comprehensive review and update. J. Allergy Clin. Immunol. (IF 11.4) Pub Date : 2024-07-06 Jihane Adelon,Hassan Abolhassani,Saliha Esenboga,Fanny Fouyssac,Deniz Cagdas,Ilhan Tezcan,Barıs Kuskonmaz,Duygu Cetinkaya,Felipe Suarez,Seyed Alireza Mahdaviani,Samira Plassart,Anne-Laure Mathieu,Nicole Fabien,Christophe Malcus,Florence Morfin-Sherpa,Geneviève Billaud,Maud Tusseau,Sarah Benezech,Thierry Walzer,Jean-Pierre De Villartay,Yves Bertrand,Alexandre Belot
BACKGROUND DNA-dependent protein kinase catalytic subunit (DNA-PKcs) has an essential role in the non-homologous end-joining pathway that repairs DNA double-strand breaks in V(D)J recombination involved in the expression of T- and B-cell receptors. Whereas homozygous mutations in Prkdc define the Scid mouse, a model that has been widely used in biology, human mutations in PRKDC are extremely rare and
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Inhibition of mast cell degranulation by novel small molecule MRGPRX2 antagonists. J. Allergy Clin. Immunol. (IF 11.4) Pub Date : 2024-07-05 Joshua Wollam,Michelle Solomon,Christiane Villescaz,Marion Lanier,Samantha Evans,Corinne Bacon,David Freeman,Alexis Vasquez,Alan Vest,Jim Napora,Brittney Charlot,Christine Cavarlez,Andrew Kim,Lisa Dvorak,Brandon Selfridge,Liming Huang,Andres Nevarez,Harry Dedman,Jennifer Brooks,Stefan Frischbutter,Martin Metz,Nadine Serhan,Nicolas Gaudenzio,Gregg Timony,Esther Martinborough,Marcus F Boehm,Veena Viswanath
BACKGROUND Mas-related G protein-coupled receptor X2 (MRGPRX2) is a promiscuous receptor on mast cells that mediates IgE-independent degranulation and has been implicated in multiple mast cell-mediated disorders, including chronic urticaria, atopic dermatitis, and pain disorders. Although it is a promising therapeutic target, few potent, selective, small molecule antagonists have been identified, and
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Dendritic cells in food allergy, treatment, and tolerance. J. Allergy Clin. Immunol. (IF 11.4) Pub Date : 2024-07-05 Elise G Liu,Xiangyun Yin,Emily R Siniscalco,Stephanie C Eisenbarth
Food allergy is a growing problem with limited treatment options. It is important to understand the mechanisms of food tolerance and allergy to promote the development of directed therapies. Dendritic cells (DCs) are specialized antigen-presenting cells (APCs) that prime adaptive immune responses, such as those involved in the development of oral tolerance and food allergies. The DC subsets in the
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Breathing unequal: Unmasking the link between environmental justice, air pollution, and asthma severity. J. Allergy Clin. Immunol. (IF 11.4) Pub Date : 2024-06-29 Joseph S Wilson,Marissa Hauptman
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Indoor air: Guidelines, policies, and regulation. J. Allergy Clin. Immunol. (IF 11.4) Pub Date : 2024-06-29 Nicholas J Nassikas,Elliott Horner,Mary B Rice
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Phase 1/2 trials of human bone marrow-derived clonal mesenchymal stem cells for treatment of adults with moderate to severe atopic dermatitis. J. Allergy Clin. Immunol. (IF 11.4) Pub Date : 2024-06-27 Hyun-Min Seo,Bark-Lynn Lew,Yang Won Lee,Sang Wook Son,Chang Ook Park,Young Lip Park,Jin-Ok Baek,Min Kyung Shin,Dong Hyun Kim,Dong Hun Lee,Yong Hyun Jang,Hyun-Chang Ko,Chan-Ho Na,Young-Joon Seo,Dong-Sik Ham,Dong-Jun Kim,Gwang Seong Choi
BACKGROUND Mesenchymal stem cells (MSCs) play important roles in therapeutic applications by regulating immune responses. OBJECTIVE We investigated the safety and efficacy of allogenic human bone marrow-derived clonal MSCs (hcMSCs) in subjects with moderate to severe atopic dermatitis (AD). METHODS The study included a phase 1 open-label trial followed by a phase 2 randomized, double-blind, placebo-controlled