Browsing by Subject "anaphylaxis"

Now showing 1 - 7 of 7
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    Interleukin-13 Is Unlucky for Allergy Sufferers
    (Elsevier, 2019-10) Xie, Markus M.; Dent, Alexander L.; Microbiology and Immunology, School of Medicine
    Anaphylaxis, a life-threatening allergic reaction, is dependent on high affinity allergen-specific IgE. Gowthaman et al . now show that a new interleukin (IL)-13-expressing T helper cell subset specifically promotes high-affinity IgE responses. The discovery of T follicular helper (Tfh)13 cells defines potential new targets for allergy therapies.
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    Management of food allergy in the school setting
    (OceanSide, 2020-09-01) Huddleston, Christina M.; Kloepfer, Kirsten M.; Jin, Jay J.; Vitalpur, Girish V.; Pediatrics, School of Medicine
    Food allergy is a growing health and safety concern that affects up to 8% of school-age children. Because children spend a significant part of their day in school, and the overall number of school-age children with food allergy has been increasing, management of food allergies relies on the collaboration of allergists, families, and schools to treat and prevent acute allergic reactions. For schools, this involves policies centered on food allergen avoidance, preparedness with epinephrine autoinjectors, adequate school personnel training, and accommodations for an equal opportunity learning environment. Partnerships with allergists, primary care providers, students, families, school nurses, and school staff are vital for creating individualized and effective care plans that will allow all children, including those with food allergies, a safe and nurturing learning environment.
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    Mechanism for Initiation of Food Allergy: Dependence on skin barrier mutations and environmental allergen co-stimulation
    (Elsevier, 2018) Walker, Matthew; Green, Jeremy; Ferrie, Ryan; Queener, Ashley; Kaplan, Mark H.; Cook-Mills, Joan M.; Pediatrics, School of Medicine
    Background Mechanisms for the development of food allergy in neonates are unknown but are clearly linked in patient populations to a genetic predisposition towards skin barrier defects. Whether skin barrier defects functionally contribute to development of food allergy is unknown. Objective The purpose of the study was to determine whether skin barrier mutations, that are primarily heterozygous in patient populations, contribute to the development of food allergy. Methods Mice heterozygous for the Flgft and Tmem79ma mutations were skin sensitized with environmental allergens and food allergens. After sensitization, mice received oral challenge with food allergen and then inflammation, inflammatory mediators, and anaphylaxis were measured. Results We define development of inflammation, inflammatory mediators, and food allergen-induced anaphylaxis in neonatal mice with skin barrier mutations following brief concurrent cutaneous exposure to food and environmental allergens. Moreover, neonates of allergic mothers have elevated responses to suboptimal sensitization with food allergens. Importantly, the responses to food allergens by these neonatal mice were dependent on genetic defects in skin barrier function and on exposure to environmental allergens. Blockade of ST2 during skin sensitization inhibited development of anaphylaxis, antigen-specific IgE and inflammatory mediators. The neonatal anaphylactic responses and antigen-specific IgE were also inhibited by oral pre-exposure to food allergen but, interestingly, this was blunted by concurrent pre-exposure of the skin to environmental allergen. Conclusion These studies uncover mechanisms for food allergy sensitization and anaphylaxis in neonatal mice that are consistent with features of human early life exposures and genetics in clinical food allergy and demonstrate that changes in barrier function drive development of anaphylaxis to food allergen.
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    Mechanisms for Alternaria alternata Function in the Skin During Induction of Peanut Allergy in Neonatal Mice With Skin Barrier Mutations
    (Frontiers, 2021-09) Buelow, Lauren M.; Hoji, Akihiko; Tat, Kiet; Schroeder-Carter, Lindsay M.; Carroll, Daniela J.; Cook-Mills, Joan M.; Pediatrics, School of Medicine
    Neonatal mice with heterozygous mutations in genes encoding the skin barrier proteins filaggrin and mattrin (flaky tail mice [FT+/−]) exhibit oral peanut-induced anaphylaxis after skin sensitization. As we have previously reported, sensitization in this model is achieved via skin co- exposure to the environmental allergen Alternaria alternata (Alt), peanut extract (PNE), and detergent. However, the function of Alt in initiation of peanut allergy in this model is little understood. The purpose of this study was to investigate candidate cytokines induced by Alt in the skin and determine the role of these cytokines in the development of food allergy, namely oncostatin M (Osm), amphiregulin (Areg), and IL-33. RT-qPCR analyses demonstrated that skin of FT+/− neonates expressed Il33 and Osm following Alt or Alt/PNE but not PNE exposure. By contrast, expression of Areg was induced by either Alt, PNE, or Alt/PNE sensitization in FT+/− neonates. In scRNAseq analyses, Osm, Areg, and Il33 were expressed by several cell types, including a keratinocyte cluster that was expanded in the skin of Alt/PNE-exposed FT+/− pups as compared to Alt/PNE-exposed WT pups. Areg and OSM were required for oral PNE-induced anaphylaxis since anaphylaxis was inhibited by administration of neutralizing anti-Areg or anti-OSM antibodies prior to each skin sensitization with Alt/PNE. It was then determined if intradermal injection of recombinant IL33 (rIL33), rAreg, or rOSM in the skin could substitute for Alt during skin sensitization to PNE. PNE skin sensitization with intradermal rIL33 was sufficient for oral PNE-induced anaphylaxis, whereas skin sensitization with intradermal rAreg or rOSM during skin exposure to PNE was not sufficient for anaphylaxis to oral PNE challenge. Based on these studies a pathway for IL33, Areg and OSM in Alt/PNE sensitized FT+/− skin was defined for IgE induction and anaphylaxis. Alt stimulated two pathways, an IL33 pathway and a pathway involving OSM and Areg. These two pathways acted in concert with PNE to induce food allergy in pups with skin barrier mutations.
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    Multicenter prevalence of anaphylaxis in clinic-based oral food challenges
    (Elsevier, 2017-10-01) Akuete, Kwei; Guffey, Danielle; Israelsen, Ryan B.; Broyles, John M.; Higgins, Lori Jo; Green, Todd D.; Naimi, David R.; MacGinnitie, Andrew J.; Vitalpur, Girish; Minard, Charles G.; Davis, Carla M.; Pediatrics, School of Medicine
    Background Although previous single-center studies report the rate of anaphylaxis for oral food challenges (OFCs) as 9% to 11%, little is known regarding the epidemiology of clinical OFCs across multiple centers in the United States. Objective To examine the epidemiology, symptoms, and treatment of clinical low-risk OFCs in the nonresearch setting. Methods Data were obtained from 2008 to 2013 through a physician survey in 5 food allergy centers geographically distributed across the United States. Allergic reaction rates and the association of reaction rates with year, hospital, and demographics were determined using a linear mixed model. Meta-analysis was used to pool the proportion of reactions and anaphylaxis with inverse-variance weights using a random-effects model with exact confidence intervals (CIs). Results A total of 6,377 OFCs were performed, and the pooled estimate of anaphylaxis was 2% (95% CI, 1%-3%). The rate of allergic reactions was 14% (95% CI, 13%-16%) and was consistent during the study period (P = .40). Reaction rates ranged from 13% to 33%. Males reacted 16% more frequently than females (95% CI, 4%-37.5%; P = .04). Foods challenged in 2013 varied geographically, with peanut as the most challenged food in the Northeast, Midwest, and West and egg as the most challenged in the South. Conclusion As the largest national survey of allergic reactions of clinical open OFCs in a nonresearch setting in the United States, this study found that performing clinical nonresearch open low-risk OFCs results in few allergic reactions, with 86% of challenges resulting in no reactions and 98% without anaphylaxis.
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    Prevalence of Errors in Anaphylaxis in Kids (PEAK): A Multicenter Simulation-Based Study
    (Elsevier, 2020-04) Maa, Tensing; Scherzer, Daniel; Harwayne-Gidansky, Ilana; Capua, Tali; Kessler, David O.; Trainor, Jennifer L.; Jani, Priti; Damazo, Becky; Abulebda, Kamal; Diaz, Maria Carmen G.; Sharara-Chami, Rana; Srinivasan, Sushant; Zurca, Adrian; Deutsch, Ellen S.; Hunt, Elizabeth A.; Auerbach, Marc; Pediatrics, School of Medicine
    Background Multi-institutional, international practice variation of pediatric anaphylaxis management by health care providers has not been reported. Objective To characterize variability in epinephrine administration for pediatric anaphylaxis across institutions, including frequency and types of medication errors. Methods A prospective, observational, study using a standardized in situ simulated anaphylaxis scenario was performed across 28 health care institutions in 6 countries. The on-duty health care team was called for a child (patient simulator) in anaphylaxis. Real medications and supplies were obtained from their actual locations. Demographic data about team members, institutional protocols for anaphylaxis, timing of epinephrine delivery, medication errors, and systems safety issues discovered during the simulation were collected. Results Thirty-seven in situ simulations were performed. Anaphylaxis guidelines existed in 41% (15 of 37) of institutions. Teams used a cognitive aid for medication dosing 41% (15 of 37) of the time and 32% (12 of 37) for preparation. Epinephrine autoinjectors were not available in 54% (20 of 37) of institutions and were used in only 14% (5 of 37) of simulations. Median time to epinephrine administration was 95 seconds (interquartile range, 77-252) for epinephrine autoinjector and 263 seconds (interquartile range, 146-407.5) for manually prepared epinephrine (P = .12). At least 1 medication error occurred in 68% (25 of 37) of simulations. Nursing experience with epinephrine administration for anaphylaxis was associated with fewer preparation (P = .04) and administration (P = .01) errors. Latent safety threats were reported by 30% (11 of 37) of institutions, and more than half of these (6 of 11) involved a cognitive aid. Conclusions A multicenter, international study of simulated pediatric anaphylaxis reveals (1) variation in management between institutions in the use of protocols, cognitive aids, and medication formularies, (2) frequent errors involving epinephrine, and (3) latent safety threats related to cognitive aids among multiple sites.
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    ROCK1 via LIM kinase regulates growth, maturation and actin based functions in mast cells
    (Impact Journals, LLC, 2016-03-29) Kapur, Reuben; Shi, Jianjian; Ghosh, Joydeep; Munugalavadla, Veerendra; Sims, Emily; Martin, Holly; Wei, Lei; Mali, Raghuveer Singh; Department of Pediatrics, IU School of Medicine
    Understanding mast cell development is essential due to their critical role in regulating immunity and autoimmune diseases. Here, we show how Rho kinases (ROCK) regulate mast cell development and can function as therapeutic targets for treating allergic diseases. Rock1 deficiency results in delayed maturation of bone marrow derived mast cells (BMMCs) in response to IL-3 stimulation and reduced growth in response to stem cell factor (SCF) stimulation. Further, integrin-mediated adhesion and migration, and IgE-mediated degranulation are all impaired in Rock1-deficient BMMCs. To understand the mechanism behind altered mast cell development in Rock1-/- BMMCs, we analyzed the activation of ROCK and its downstream targets including LIM kinase (LIMK). We observed reduced activation of ROCK, LIMK, AKT and ERK1/2 in Rock1-deficient BMMCs in response to SCF stimulation. Further, loss of either Limk1 or Limk2 also demonstrated altered BMMC maturation and growth; combined deletion of both Limk1 and Limk2 resulted in further reduction in BMMC maturation and growth. In passive cutaneous anaphylaxis model, deficiency of Rock1 or treatment with ROCK inhibitor Fasudil protected mice against IgE-mediated challenge. Our results identify ROCK/LIMK pathway as a novel therapeutic target for treating allergic diseases involving mast cells.