US antibiotic stewardship and penicillin allergy.

Purpose of review: The purpose of this review is to improve otolaryngologists' antibiotic stewardship by detailing current approaches to penicillin allergy. Recent findings: Although up to 15% of hospitalized patients in the United States have a penicillin allergy recorded on their charts, fewer than 10% of these have a true penicillin allergy. Summary: Using a combination of a detailed allergy history, skin testing and graded-dose administration, many patients whose charts say 'penicillin-allergic' can safely be treated with penicillin and cross-reacting antibiotics. This permits use of narrower-spectrum antibiotics and saves money. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Steroid Resistance of Airway Type 2 Innate Lymphoid Cells (ILC2s) from Severe Asthma: The Role of Thymic Stromal cell Lymphopoietin (TSLP)

Publication date: Available online 20 April 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Sucai Liu, Mukesh Verma, Lidia Michalec, Weimin Liu, Anand Sripada, Donald Rollins, James Good, Yoko Ito, HongWei Chu, Magdalena M. Gorska, Richard J. Martin, Rafeul Alam
BackgroundILC2s represent an important type 2 immune cell. Glucocorticoid regulation of human ILC2s is largely unknown.ObjectiveTo assess steroid resistance of human blood and airway ILC2s from asthmatic patients and examine its mechanism of induction.MethodsWe studied human blood and lung ILC2s from asthmatic and control subjects by flow cytometry and ELISA.ResultsDexamethasone (Dex) inhibited (P=0.04) CRTH2 and type 2 cytokine expression by blood ILC2s stimulated with IL25 and IL33. However, it failed to do so when ILC2s were stimulated with IL7 and TSLP, two ligands of IL7Rα. Unlike blood ILC2s, BAL ILC2s from asthmatic patients were resistant to Dex. BAL from the asthmatic patients had elevated TSLP but not IL7. The BAL TSLP level correlated (r=0.74) with steroid resistance of ILC2s. TSLP was synergistically induced in epithelial cells by IL13 and human rhinovirus. Mechanistically, Dex upregulated ILC2 expression of IL7Rα , which augmented and sustained STAT5 signaling by TSLP. TSLP induced MEK, c-Fos, ID3, pSTAT3 and pSTAT5—molecules linked to steroid resistance. Dex inhibited c-Fos, ID3 and pSTAT3, but not pSTAT5 and MEK. The MEK inhibitor Trametinib, the JAK-STAT inhibitor Tofacitinib and the STAT5 inhibitor Pimozide reversed steroid resistance of BAL ILC2s.ConclusionsDex inhibited type 2 cytokine production by blood ILC2s. IL7 and TSLP abrogated this inhibition and induced steroid resistance of ILC2s in a MEK and STAT5-dependent manner. BAL ILC2s from asthmatic patients with elevated TSLP were steroid resistant, which was reversed by clinically available inhibitors of MEK and STAT5.

Teaser

Dexamethasone inhibited CRTH2 and IL5 but promoted IL7Rα expression by ILC2s, which led to the development of steroid resistance This steroid resistance was reversed by MEK and STAT5 inhibitors.


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Type 3 innate lymphoid cells induce proliferation of CD94+ NK cells

Publication date: Available online 20 April 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Shuo Li, Hideaki Morita, Beate Rückert, tadech boonpiyathad, Avidan Neumann, Cezmi Akdis




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Direct monitoring of basophil degranulation by using avidin-based probes

Publication date: Available online 20 April 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Régis Joulia, Claire Mailhol, Salvatore Valitutti, Alain Didier, Eric Espinosa

Teaser

We show that fluorescent avidin binds to basophil cell surface upon degranulation and can be used to set up a new basophil activation test (BAT). This new assay provides results comparable to those provided by the CD63 exposure-based BAT, but has the advantage to directly monitor granule exteriorization.


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Asthma: the past, the future, the environment, and the costs

Publication date: Available online 20 April 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Eyal Shemesh, Lawrence C. Kleinman




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Vitamin D downregulates the IL-23 receptor pathway in human mucosal ILC3

Publication date: Available online 20 April 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Viktoria Konya, Paulo Czarnewski, Marianne Forkel, Anna Rao, Efthymia Kokkinou, Eduardo J. Villablanca, Sven Almer, Ulrik Lindforss, Danielle Friberg, Charlotte Höög, Peter Bergman, Jenny Mjösberg
BackgroundVitamin D deficiency is a risk factor for inflammatory bowel disease (IBD). The IL-23-driven tissue-resident ILC3 play essential roles in intestinal immunity, and targeting IL-23/12 is a promising approach in IBD therapy.ObjectiveWe set out to define the role of 1α,25-dihydroxy vitamin D3 (1,25D) in regulating functional responses of human mucosal ILC3 to IL-23 plus IL-1β stimulation.MethodsTranscriptomes of sorted tonsil ILC3 were assessed by microarray analysis. ILC3 cytokine production, proliferation and differentiation were determined by flow cytometry, ELISA and multiplex immunoassay. Intestinal cell suspensions and ILC3 sorted from gut biopsies of IBD patients were also analyzed along with plasma 25-hydroxy vitamin D3 (25D) detection.ResultsILC3 stimulated with IL-23 plus IL-1β upregulated the vitamin D receptor (VDR) and responded to 1,25D with downregulation of the IL-23 receptor (IL-23R) pathway. Consequently, 1,25D suppressed the IL-22, IL-17F and GM-CSF production from tonsil and gut ILC3. In parallel, 1,25D upregulated genes linked to the IL-1β signaling pathway as well as the IL-1β-inducible cytokines IL-6, IL-8 and MIP-1α/β. The 1,25D-triggered skewing in ILC3 function was not accompanied or caused by changes in viability, proliferation or phenotype. Finally, we confirmed low 25D plasma levels in IBD patients with active inflammation.ConclusionIn the light of the beneficial targeting of IL-23/12 in IBD, 1,25D appears as an interesting therapeutic agent that inhibits the IL-23R pathway, providing a novel mechanism for how ILC3 could be manipulated to regulate intestinal inflammation.

Teaser

We have unraveled the detailed mechanisms behind how vitamin D efficiently suppresses IL-23 receptor signaling in gut innate lymphoid cells, providing incitement for vitamin D supplementation as a therapeutic approach in IBD.


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Allergens involved in the cross-reactivity of Aedes aegypti with other arthropods

Publication date: Available online 20 April 2017
Source:Annals of Allergy, Asthma & Immunology
Author(s): Jose Fernando Cantillo, Leonardo Puerta, Sylvie Lafosse-Marin, Jose Luis Subiza, Luis Caraballo, Enrique Fernandez-Caldas
BackgroundCross-reactivity between Aedes aegypti and mites, cockroaches, and shrimp has been previously suggested, but the involved molecular components have not been fully described.ObjectiveTo evaluate the cross-reactivity between A aegypti and other arthropods.MethodsThirty-four serum samples from patients with asthma and/or allergic rhinitis were selected, and specific IgE to A aegypti, Dermatophagoides pteronyssinus, Dermatophagoides farinae, Blomia tropicalis, Periplaneta americana. and Litopenaeus vannamei was measured by enzyme-linked immunosorbent assay. Cross-reactivity was investigated using pooled serum samples from allergic patients, allergenic extracts, and the recombinant tropomyosins (Aed a 10.0201, Der p 10, Blo t 10, Lit v 1, and Per a 7). Four IgE reactive bands were further characterized by matrix-assisted laser desorption/ionization tandem time of flight.ResultsFrequency of positive IgE reactivity was 82.35% to at least one mite species, 64.7% to A aegypti, 29.4% to P americana, and 23.5% to L vannamei. The highest IgE cross-reactivity was seen between A aegypti and D pteronyssinus (96.6%) followed by L vannamei (95.4%), B tropicalis (84.4%), and P americana (75.4%). Recombinant tropomyosins from mites, cockroach, or shrimp inhibited the IgE reactivity to the mosquito at a lower extent than the extracts from these arthropods. Several bands of A aegypti cross-reacted with arthropod extracts, and 4 of them were identified as odorant binding protein, mitochondrial cytochrome C, peptidyl-prolyl cis-trans isomerase, and protein with hypothetical magnesium ion binding function.ConclusionWe identified 4 novel cross-reactive allergens in A aegypti allergenic extract. These molecules could influence the manifestation of allergy to environmental allergens in the tropics.



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