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pubmed: 0091-6749



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The antimicrobial peptide hBD2 promotes itch through Toll-like receptor 4 signaling in mice.
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The antimicrobial peptide hBD2 promotes itch through Toll-like receptor 4 signaling in mice.

J Allergy Clin Immunol. 2017 Apr 22;:

Authors: Feng J, Luo J, Mack MR, Yang P, Zhang F, Wang G, Gong X, Cai T, Mei Z, Kim BS, Yin S, Hu H

Abstract
The psoriasis biomarker hBD2 produces a robust scratching response in a TLR4-dependent manner in mice. TRPV1 is a downstream mediator of hBD2-induced itch. These findings suggest that hBD2 might act as an endogenous pruritogen in psoriatic itch.

PMID: 28442325 [PubMed - as supplied by publisher]




Pathogenic CD4(+) T cells in patients with asthma.
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Pathogenic CD4(+) T cells in patients with asthma.

J Allergy Clin Immunol. 2017 Apr 22;:

Authors: Muehling LM, Lawrence MG, Woodfolk JA

Abstract
Asthma encompasses a variety of clinical phenotypes that involve distinct T cell-driven inflammatory processes. Improved understanding of human T-cell biology and the influence of innate cytokines on T-cell responses at the epithelial barrier has led to new asthma paradigms. This review captures recent knowledge on pathogenic CD4(+) T cells in asthmatic patients by drawing on observations in mouse models and human disease. In patients with allergic asthma, TH2 cells promote IgE-mediated sensitization, airway hyperreactivity, and eosinophilia. Here we discuss recent discoveries in the myriad molecular pathways that govern the induction of TH2 differentiation and the critical role of GATA-3 in this process. We elaborate on how cross-talk between epithelial cells, dendritic cells, and innate lymphoid cells translates to T-cell outcomes, with an emphasis on the actions of thymic stromal lymphopoietin, IL-25, and IL-33 at the epithelial barrier. New concepts on how T-cell skewing and epitope specificity are shaped by multiple environmental cues integrated by dendritic cell "hubs" are discussed. We also describe advances in understanding the origins of atypical TH2 cells in asthmatic patients, the role of TH1 cells and other non-TH2 types in asthmatic patients, and the features of T-cell pathogenicity at the single-cell level. Progress in technologies that enable highly multiplexed profiling of markers within a single cell promise to overcome barriers to T-cell discovery in human asthmatic patients that could transform our understanding of disease. These developments, along with novel T cell-based therapies, position us to expand the assortment of molecular targets that could facilitate personalized treatments.

PMID: 28442213 [PubMed - as supplied by publisher]




Clinical predictors of remission and persistence of adult-onset asthma.
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Clinical predictors of remission and persistence of adult-onset asthma.

J Allergy Clin Immunol. 2017 Apr 21;:

Authors: Westerhof GA, Coumou H, de Nijs SB, Weersink E, Bel EH

Abstract
BACKGROUND: Adult-onset asthma is an important but relatively understudied asthma phenotype and little is known about its natural course and prognosis. The remission rate is believed to be low, and it is still obscure which factors predict remission or persistence of the disease.
OBJECTIVE: To determine the remission rate, and identify predictors of persistence and remission of adult-onset asthma.
METHODS: Two hundred adult patients with recently diagnosed (<1 year) asthma were recruited from secondary and tertiary pulmonary clinics and prospectively followed for 5 years. Clinical, functional and inflammatory parameters were assessed at baseline and at yearly visits. Asthma remission was defined as absence of asthma symptoms for ≥1 year and no asthma medication use for ≥1 year. Descriptive statistics and logistic regression analysis were performed.
RESULTS: Five-year follow-up data of 170 patients (85%) was available. Of these, 27 patients (15.9%) experienced asthma remission. Patients with asthma persistence were older, had worse asthma control, required higher doses of inhaled corticosteroids, had more severe airway hyperresponsiveness, more often nasal polyps and higher levels of blood neutrophils as compared to patients who experienced clinical remission. In a multivariable logistic regression analysis, only moderate-severe bronchial hyperresponsiveness and nasal polyps were independent predictors of asthma persistence. Patients with these two characteristics had less than 1% chance of asthma remission.
CONCLUSION: One in six patients with adult-onset asthma experiences remission within the first 5 years of the disease. In patients with moderate to severe bronchial hyperresponsiveness and nasal polyposis the chance of remission is close to zero.

PMID: 28438546 [PubMed - as supplied by publisher]




Direct monitoring of basophil degranulation by using avidin-based probes.
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Direct monitoring of basophil degranulation by using avidin-based probes.

J Allergy Clin Immunol. 2017 Apr 19;:

Authors: Joulia R, Mailhol C, Valitutti S, Didier A, Espinosa E

Abstract
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.

PMID: 28433691 [PubMed - as supplied by publisher]




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

J Allergy Clin Immunol. 2017 Apr 19;:

Authors: Shemesh E, Kleinman LC

PMID: 28433690 [PubMed - as supplied by publisher]




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

J Allergy Clin Immunol. 2017 Apr 19;:

Authors: Li S, Morita H, Rückert B, Boonpiyathad T, Neumann A, Akdis C

PMID: 28433689 [PubMed - as supplied by publisher]




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

J Allergy Clin Immunol. 2017 Apr 19;:

Authors: Konya V, Czarnewski P, Forkel M, Rao A, Kokkinou E, Villablanca EJ, Almer S, Lindforss U, Friberg D, Höög C, Bergman P, Mjösberg J

Abstract
BACKGROUND: Vitamin 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.
OBJECTIVE: We 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.
METHODS: Transcriptomes 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.
RESULTS: ILC3 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.
CONCLUSION: In 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.

PMID: 28433688 [PubMed - as supplied by publisher]




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

J Allergy Clin Immunol. 2017 Apr 19;:

Authors: Liu S, Verma M, Michalec L, Liu W, Sripada A, Rollins D, Good J, Ito Y, Chu H, Gorska MM, Martin RJ, Alam R

Abstract
BACKGROUND: ILC2s represent an important type 2 immune cell. Glucocorticoid regulation of human ILC2s is largely unknown.
OBJECTIVE: To assess steroid resistance of human blood and airway ILC2s from asthmatic patients and examine its mechanism of induction.
METHODS: We studied human blood and lung ILC2s from asthmatic and control subjects by flow cytometry and ELISA.
RESULTS: Dexamethasone (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.
CONCLUSIONS: Dex 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.

PMID: 28433687 [PubMed - as supplied by publisher]




Food protein induced enterocolitis syndrome in Australia: A population based study 2012-2014.
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Food protein induced enterocolitis syndrome in Australia: A population based study 2012-2014.

J Allergy Clin Immunol. 2017 Apr 17;:

Authors: Mehr S, Frith K, Barnes EH, Campbell DE, FPIES STUDY GROUP

Abstract
BACKGROUND: Food protein induced enterocolitis syndrome (FPIES) is a non-IgE mediated gastrointestinal allergic disorder. Large population based FPIES studies are lacking.
OBJECTIVE: To determine the incidence and clinical characteristics of FPIES in Australian infants METHODS: An Australia wide survey (2012-2014) was undertaken via the Australian Paediatric Surveillance Unit, with monthly notification of new cases of acute FPIES in infants aged <24 months by 1400 participating Paediatricians.
RESULTS: 230 infants with FPIES were identified. The incidence of FPIES in Australian infants (<24 months) was 15.4/100,000/year. Median age of first episode, diagnosis and notification were 5, 7 and 10 months respectively. There was no gender predilection. 7% of infants had siblings with a history of FPIES and 5% reacted during exclusive breastfeeding. 68% had a single food trigger (20% two, 12% three or more food triggers). The most common FPIES triggers were rice (45%), cow's milk (33%) and egg (12%). 51% of infants reacted on their first known exposure. Infants with FPIES to multiple versus single food groups were younger at initial episode (4.6 vs. 5.8 months, P=0.001) and more frequently had fruit and/or vegetable FPIES (66% vs. 21%, p<0.0001). Infants exclusively breastfed for more than 4 months had a trend to lower rates of FPIES to multiple food groups (23% vs. 36%, P=0.06). 64% of infants with multiple FPIES which included cow's milk FPIES had co-associated solid food FPIES. 42% of infants with fish-FPIES had reacted to other food groups.
CONCLUSIONS: FPIES is not rare, with an estimated incidence of 15.4/100,000/year. Rice is the most common food trigger in Australia. Factors associated with multiple-FPIES included early onset disease and FPIES to fruits and/or vegetables.

PMID: 28427879 [PubMed - as supplied by publisher]




Hypersensitivity transfusion reactions due to IgA deficiency are rare according to French hemovigilance data.
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Hypersensitivity transfusion reactions due to IgA deficiency are rare according to French hemovigilance data.

J Allergy Clin Immunol. 2017 Apr 13;:

Authors: Tacquard C, Boudjedir K, Carlier M, Muller JY, Gomis P, Mertes PM

Abstract
In an analysis of a large French hemovigilance database (2004-2014), hypersensitivity transfusion reactions (HTRs) due to IgA deficiency were extremely rare with an frequency far lower than reported so far. In depth investigation of HTRs for IgA deficiency should be limited to moderate to severe recurrent reactions.

PMID: 28414063 [PubMed - as supplied by publisher]




Novel PIK3CD mutations affecting N-terminal residues of p110δ cause APDS1 in humans.
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Novel PIK3CD mutations affecting N-terminal residues of p110δ cause APDS1 in humans.

J Allergy Clin Immunol. 2017 Apr 13;:

Authors: Takeda AJ, Zhang Y, Dornan GL, Siempelkamp BD, Jenkins ML, Matthews HF, McElwee JJ, Bi W, Seeborg FO, Su HC, Burke JE, Lucas CL

Abstract
APDS is a newly described and prevalent primary immunodeficiency disease, and we now expand the list of mutation sites to include E81K and G124D of p110δ and uncover an intramolecular mechanism of activation that is inhibited by clinically relevant targeting of p110δ.

PMID: 28414062 [PubMed - as supplied by publisher]




Mechanistic Correlates of Clinical Responses to Omalizumab in the Setting of Oral Immunotherapy for Milk Allergy.
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Mechanistic Correlates of Clinical Responses to Omalizumab in the Setting of Oral Immunotherapy for Milk Allergy.

J Allergy Clin Immunol. 2017 Apr 13;:

Authors: Frischmeyer-Guerrerio PA, Masilamani M, Gu W, Brittain E, Wood R, Kim J, Nadeau K, Jarvinen KM, Grishin A, Lindblad R, Sampson HA

Abstract
BACKGROUND: In our recent clinical trial, the addition of omalizumab to oral immunotherapy (OIT) for milk allergy improved safety but no significant clinical benefit was detected.
OBJECTIVE: To investigate mechanisms by which omalizumab modulates immunity in the context of OIT, and to identify baseline biomarkers that predict subgroups of patients most likely to benefit from omalizumab.
METHODS: Blood was obtained at baseline and multiple time-points during a placebo-controlled trial of OIT for milk allergy where subjects were randomized to receive omalizumab or placebo. Immunologic outcomes included measurement of basophil CD63 expression and histamine release (HR), and casein-specific CD4(+) T regulatory (Treg) cell proliferation. Biomarkers were analyzed in relationship to measurements of safety and efficacy.
RESULTS: Milk-induced basophil CD63 expression was transiently reduced in whole blood samples from both omalizumab and placebo subjects. However, IgE-dependent HR increased in washed cell preparations from omalizumab but not placebo subjects. No increase in Treg frequency was evident in either group. Subjects with lower rates of adverse reactions, regardless of arm, experienced better clinical outcomes. Pre-OIT basophil reactivity positively associated with occurrence of symptoms during OIT, while the baseline milk IgE/total IgE ratio correlated with the likelihood of achieving sustained unresponsiveness (SU). A combination of baseline basophil and serologic biomarkers defined a subset of patients where adjunctive therapy with omalizumab was associated with attainment of SU and a reduction in adverse reactions.
CONCLUSIONS: Combining omalizumab therapy with milk OIT led to distinct alterations in basophil reactivity but not T cell responses. Baseline biomarkers may identify subjects most likely to benefit from adjunctive therapy with omalizumab.

PMID: 28414061 [PubMed - as supplied by publisher]




Systems Approach to Uncover Signaling Networks in Primary Immunodeficiency Diseases.
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Systems Approach to Uncover Signaling Networks in Primary Immunodeficiency Diseases.

J Allergy Clin Immunol. 2017 Apr 12;:

Authors: Choi J, Fernandez R, Maecker HT, Butte MJ

Abstract
CAPSULE SUMMARY: This broad, unbiased approach of studying signaling across all circulating immune cells in healthy subjects allowed identification of disrupted signaling networks in patients with primary immunodeficiencies.

PMID: 28412396 [PubMed - as supplied by publisher]




Severe Asthma: differential chemokine response of airway epithelial cells.
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Severe Asthma: differential chemokine response of airway epithelial cells.

J Allergy Clin Immunol. 2017 Apr 12;:

Authors: Thomas B, Anthony Hirst R, H Brett-Pitt M, Williams G, Andrew PW, Sousa AR, Marshall RP, Brightling C, O'Callaghan C

Abstract
The differential chemokine response of airway basal cells of severe asthma patients to Streptococcus pneumoniae and Dermatophagoides pteronyssinus allergen may be of significance in the context of developing novel immunomodulatory therapeutic strategies for atopic asthma.

PMID: 28412395 [PubMed - as supplied by publisher]




Water-soluble chitosan inhibits nerve growth factor and attenuates allergic inflammation in mite allergen-induced allergic rhinitis.
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Water-soluble chitosan inhibits nerve growth factor and attenuates allergic inflammation in mite allergen-induced allergic rhinitis.

J Allergy Clin Immunol. 2017 Apr 12;:

Authors: Chen PC, Hsieh MH, Wen-ShuoKuo P, Kao HF, Hsu CL, Wang JY

Abstract
Nerve growth factor induces nasal inflammation by augmenting the existing TH2 immune response, and this can be suppressed bywater-soluble chitosan, a natural, nontoxic product that provides new therapy for allergic rhinitis.

PMID: 28412394 [PubMed - as supplied by publisher]




Adhesion-induced eosinophil cytolysis requires the RIPK3-MLKL signaling pathway which is counter-regulated by autophagy.
Related Articles Adhesion-induced eosinophil cytolysis requires the RIPK3-MLKL signaling pathway which is counter-regulated by autophagy. J Allergy Clin Immunol. 2017 Apr 12;: Authors: Radonjic-Hoesli S, Wang X, de Graauw E, Stoeckle C, Styp-Rekowska B, Hlushchuk R, Simon D, Spaeth PJ, Yousefi S, Simon HU Abstract BACKGROUND: Eosinophils are a subset of granulocytes which can be involved in the pathogenesis of different diseases, including allergy. Their effector functions are closely linked to their cytotoxic granule proteins. The release takes place by several different mechanisms, one of which is cytolysis, which is associated with the release of intact granules, so-called clusters of free eosinophil granules. The mechanism underlying this activation-induced form of cell death in eosinophils has remained unclear. OBJECTIVE: We aimed to elucidate the molecular mechanism of eosinophil cytolysis. METHODS: Isolated blood eosinophils were incubated on glass cover slips coated with intravenous immunoglobulin (IVIG) and inactive complement component 3b (iC3b). A morphological characterization of the distinct stages of the proposed cascade was addressed by means of time-lapse automated fluorescence microscopy, electron microscopy, and immunohistochemistry. Experiments with pharmacological inhibitors were performed to elucidate the sequence of events within the cascade. Tissue samples of patients suffering from eosinophilic skin diseases or eosinophilic esophagitis were used for in vivo analyses. RESULTS: Following eosinophil adhesion, we observed reactive oxygen species (ROS) production, early degranulation, and granule fusion processes leading to a distinct morphology exhibiting cytoplasmic vacuolization and, finally, to cytolysis. Using a pharmacological approach, we demonstrate the presence of a receptor-interacting protein kinase 3 (RIPK3) - mixed lineage kinase-like (MLKL) signaling pathway in eosinophils, which, following its activation, leads to the production of high levels of reactive oxygen species (ROS) in a p38 mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3'-kinase (PI3K) - dependent manner. All these steps are required for cytoplasmic vacuolization and subsequent cytolysis to occur. Interestingly, triggering cytolysis is associated with an induction of autophagy in eosinophils and additional stimulation of autophagy by pharmacological inhibition of the mechanistic target of rapamycin (mTOR) counter-regulates cell death. Moreover, MLKL phosphorylation, cytoplasmic vacuolization, and cytolysis were observed in eosinophils under in vivo inflammatory conditions. CONCLUSION: We report that adhesion-induced eosinophil cytolysis takes place by a RIPK3-MLKL-dependent necroptosis which can be counter-regulated by autophagy. The receptor-interacting protein kinase 3 (RIPK3) - mixed lineage kinase-like (MLKL) signaling pathway mediates eosinophil cytolysis, a phenomenon often observed in eosinophilic tissues of patients suffering from diseases with eosinophil-mediated immunopathology. PMID: 28412393 [PubMed - as supplied by publisher] [...]



Diminished airway macrophage expression of the Axl receptor tyrosine kinase is associated with defective efferocytosis in asthma.
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Diminished airway macrophage expression of the Axl receptor tyrosine kinase is associated with defective efferocytosis in asthma.

J Allergy Clin Immunol. 2017 Apr 12;:

Authors: Grabiec AM, Denny N, Doherty JA, Happonen KE, Hankinson J, Connolly E, Fife ME, Fujimori T, Fujino N, Goenka A, Holden S, Tavernier G, Shah R, Cook PC, MacDonald AS, Niven RM, Dahlbäck B, Fowler SJ, Simpson A, Hussell T

Abstract
The apoptotic cell recognition receptor Axl is highly expressed on human airway/alveolar macrophages, its expression is driven by the lung microenvironment and is significantly reduced in asthma, which may explain defects in apoptotic cell clearance.

PMID: 28412392 [PubMed - as supplied by publisher]




Moving towards endotypes in atopic dermatitis: identification of patient clusters based on serum biomarker analysis.
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Moving towards endotypes in atopic dermatitis: identification of patient clusters based on serum biomarker analysis.

J Allergy Clin Immunol. 2017 Apr 12;:

Authors: Thijs JL, Strickland I, Bruijnzeel-Koomen CAFM, Nierkens S, Giovannone B, Csomor E, Sellman BR, Mustelin T, Sleeman MA, Saskia de Bruin-Weller M, Herath A, Drylewicz J, May RD, Hijnen D

Abstract
BACKGROUND: Atopic dermatitis (AD) is a complex, chronic, inflammatory skin disease with a diverse clinical presentation. It is however unclear whether this diversity exists at a biological level.
OBJECTIVE: To test the hypothesis that AD is heterogeneous at the biological level of individual inflammatory mediators.
METHODS: Serum from 193 moderate to severe adult AD patients (geomean (95%CI) SASSAD of 22.3 (21.3, 23.3) and 39.1 (37.5, 40.9) respectively) and 30 non-AD healthy controls was analysed for 147 serum mediators, total IgE and 130 allergen specific IgEs. Population heterogeneity was assessed by principal component analysis (PCA) followed by unsupervised k-means cluster analysis of the principal components.
RESULTS: AD patients showed pronounced evidence of inflammation compared to healthy controls. PCA of AD serum data revealed the presence of four potential AD patient clusters. Fifty-seven principal components (PCs) described approximately 90% of the variance. Unsupervised k-means cluster analysis of the 57 largest PCs delivered 4 distinct clusters of AD patients. Cluster 1 had high SASSAD and BSA with the highest levels of PARC, TIMP-1 and sCD14. Cluster 2 had low SASSAD with the lowest levels of IFN-α, TIMP-1 and VEGF. Cluster 3 had high SASSAD with the lowest levels of IFN-β, IL-1 and epithelial cytokines. Cluster 4 had low SASSAD but highest levels of inflammatory markers: IL-1, IL-4, IL-13 and TSLP.
CONCLUSION: AD is a heterogeneous disease both clinically and biologically. Four distinct AD patient clusters have been identified that could represent endotypes with unique biological mechanisms. Elucidation of these endotypes warrants further investigation and will require future intervention trials with specific agents such as biologics.

PMID: 28412391 [PubMed - as supplied by publisher]




Reply.
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Reply.

J Allergy Clin Immunol. 2017 Apr 11;:

Authors: Galli SJ

PMID: 28410741 [PubMed - as supplied by publisher]




Serum IgE as biomarker for predicting allergen immunotherapy effectiveness.
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Serum IgE as biomarker for predicting allergen immunotherapy effectiveness.

J Allergy Clin Immunol. 2017 Apr 11;:

Authors: Ciprandi G

PMID: 28410740 [PubMed - as supplied by publisher]




Thymus Transplantation for Complete Digeorge Syndrome: European Experience.
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Thymus Transplantation for Complete Digeorge Syndrome: European Experience.

J Allergy Clin Immunol. 2017 Apr 08;:

Authors: Davies EG, Cheung M, Gilmour K, Maimaris J, Curry J, Furmanski A, Sebire N, Halliday N, Mengrelis K, Adams S, Bernatoniene J, Bremner R, Browning M, Devlin B, Erichsen HC, Gaspar HB, Hutchison L, Ip W, Ifversen M, Leahy TR, McCarthy E, Moshous D, Neuling K, Pac M, Papadopol A, Parsley KL, Poliani L, Ricciardelli I, Sansom DM, Voor T, Worth A, Crompton T, Markert ML, Thrasher AJ

Abstract
BACKGROUND: Thymus transplantation is a promising strategy for the treatment of athymic complete DiGeorge syndrome (cDGS).
METHODS: Twelve patients with cDGS were transplanted with allogeneic cultured thymus.
OBJECTIVE: To confirm and extend the results previously obtained in a single centre.
RESULTS: Two patients died of pre-existing viral infections without developing thymopoeisis and one late death occurred from autoimmune thrombocytopaenia. One infant suffered septic shock shortly after transplant resulting in graft loss and the need for a second transplant. Evidence of thymopoeisis developed from 5-6 months after transplantation in ten patients. The median (range) of circulating naïve CD4 counts (x10(6)/L) were 44(11-440) and 200(5-310) at twelve and twenty-four months post-transplant and T-cell receptor excision circles were 2238 (320-8807) and 4184 (1582 -24596) per10(6) T-cells. Counts did not usually reach normal levels for age but patients were able to clear pre-existing and later-acquired infections. At a median of 49 months (22-80), eight have ceased prophylactic antimicrobials and five immunoglobulin replacement. Histological confirmation of thymopoeisis was seen in seven of eleven patients undergoing biopsy of transplanted tissue including five showing full maturation through to the terminal stage of Hassall body formation. Autoimmune regulator (AIRE) expression was also demonstrated. Autoimmune complications were seen in 7/12 patients. In two, early transient autoimmune haemolysis settled after treatment and did not recur. The other five suffered ongoing autoimmune problems including: thyroiditis (3); haemolysis (1), thrombocytopaenia (4) and neutropenia (1).
CONCLUSIONS: This study confirms the previous reports that thymus transplantation can reconstitute T cells in cDGS but with frequent autoimmune complications in survivors.

PMID: 28400115 [PubMed - as supplied by publisher]




Autophagy - Nobel Prize 2016 and Allergy and Asthma Research.
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Autophagy - Nobel Prize 2016 and Allergy and Asthma Research.

J Allergy Clin Immunol. 2017 Apr 08;:

Authors: Renz H

PMID: 28400114 [PubMed - as supplied by publisher]




Is IL-1β inhibition the next therapeutic target in asthma?
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Is IL-1β inhibition the next therapeutic target in asthma?

J Allergy Clin Immunol. 2017 Apr 07;:

Authors: Peebles RS

PMID: 28396074 [PubMed - as supplied by publisher]




Outcome of Hematopoietic Cell Transplantation for DNA-Double Strand Breakage Repair Disorders.
Related Articles Outcome of Hematopoietic Cell Transplantation for DNA-Double Strand Breakage Repair Disorders. J Allergy Clin Immunol. 2017 Apr 06;: Authors: Slack J, Albert MH, Balashov D, Belohradsky BH, Bertaina A, Bleesing J, Booth C, Büchner J, Buckley RH, Ouachée-Chardin M, Deripapa E, Drabko K, Eapen M, Feuchtinger T, Finocchi A, Gaspar HB, Ghosh S, Gillio A, Gonzalez-Granado LI, Grunebaum E, Güngör T, Heilmann C, Helminen M, Higuchi K, Imai K, Kalwak K, Kanazawa N, Karasu G, Kucuk ZY, Laberko A, Lange A, Mahlaoui N, Meisel R, Moshous D, Muramatsu H, Parikh S, Pasic S, Schmid I, Schuetz C, Schulz A, Schultz KR, Shaw PJ, Slatter MA, Sykora KW, Tamura S, Taskinen M, Wawer A, Wolska-Kus Nierz B, Cowan MJ, Fischer A, Gennery AR, Inborn Errors Working Party of the European Society for Blood and Marrow Transplantation, European Society for Immunodeficiencies, Stem Cell Transplant for Immunodeficiencies in Europe (SCETIDE), the Center for International Blood and Marrow Transplant Research,, Primary Immunodeficiency Treatment Consortium Abstract BACKGROUND: Rare DNA breakage-repair disorders predispose to infection and lympho-reticular malignancies. Hematopoietic cell transplantation (HCT) is curative but co-administered chemo- or radio-therapy is damaging due to systemic radio-sensitivity. We collected HCT outcome data for Nijmegen Breakage syndrome (NBS), DNA ligase IV deficiency (LIG4), Cernunnos-XLF deficiency and ataxia-telangiectasia. METHODS: Data from 38 centres worldwide, including indication, donor, conditioning regimen, graft-versus-host disease (GvHD) and outcome were analyzed. Conditioning was classified as myeloablative (MAC) if it contained radiotherapy or alkylators and reduced intensity (RIC) if no alkylators and/or fludarabine ≤150 mg/m(2) and cyclophosphamide ≤ 40 mg/kg were used. RESULTS: 55 new, 14 updated and 18 previously published patients were analyzed. Median age at HCT was 48 (range 1.5 - 552) months. 29 were transplanted for infection, 21 malignancy, 13 bone marrow failure, 13 pre-emptively, 5 had multiple indications, and 6 had no information. 22 received MAC, 59 RIC, 4 were infused;- information unavailable for 2. 73/77 patients with LIG4, Cernunnos-XLF deficiency or NBS received conditioning. Survival was 53/77 (69%), worse for MAC than RIC (p=0.006). Most deaths occurred early post-transplant suggesting poor tolerance of conditioning. Survival in ataxia-telangiectasia patients was 25%. 41/83 patients experienced aGvHD (49%): less in RIC compared to MAC, 26/56 (46%) vs 12/21 (57%) (p=0.45). Median follow-up was 35 (range 2-168) months. No secondary malignancies were reported during 15 years follow-up. Growth and developmental delay remained post-HCT; immune-mediated complications resolved. CONCLUSION: RIC-HCT resolves DNA repair disorder-associated immunodeficiency. Long-term follow-up is required for secondary malignancy surveillance. Routine HCT for ataxia-telangiectasia is not recommended. PMID: 28392333 [PubMed - as supplied by publisher] [...]



Type 2 innate Lymphoid Cells Disrupt Bronchial Epithelial Barrier Integrity by Targeting Tight Junctions Via IL-13 in Asthma.
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Type 2 innate Lymphoid Cells Disrupt Bronchial Epithelial Barrier Integrity by Targeting Tight Junctions Via IL-13 in Asthma.

J Allergy Clin Immunol. 2017 Apr 06;:

Authors: Sugita K, Steer CA, Martinez-Gonzalez I, Altunbulakli C, Morita H, Castro-Giner F, Kubo T, Wawrzyniak P, Rückert B, Sudo K, Nakae S, Matsumoto K, O'Mahony L, Akdis M, Takei F, Akdis CA

Abstract
BACKGROUND: Bronchial epithelial barrier leakiness and type 2 innate lymphoid cells (ILC2s) have been separately linked to asthma pathogenesis, however the influence of ILC2s on bronchial epithelial barrier has not been previously investigated.
OBJECTIVE: We investigated the role of ILC2s in the regulation of bronchial epithelial tight junctions (TJs) and barrier function both in bronchial epithelial cells of asthmatic and healthy individuals and general ILC- and ILC2-deficient mice.
METHODS: Co-cultures of human ILC2s and bronchial epithelial cells were used to determine transepithelial resistance (TER), paracellular flux, TJ mRNA and protein expressions. To analyze the in vivo relevance of barrier disruption by ILC2s, the effect of ILC2s on TJs was examined using a murine model of IL-33-induced airway inflammation in wild-type (WT), Rag2(-/-), Rag2(-/-)Il2rg(-/-), and Rora(sg/sg) bone marrow-transplanted (BMT) mice.
RESULTS: ILC2s significantly impaired epithelial barrier as demonstrated by reduced TER and increased FITC-dextran permeability in air-liquid interface cultures of human bronchial epithelial cells. This was in parallel to decreased mRNAs and disrupted protein expression of TJ proteins, and was restored by neutralization of IL-13. The intranasal administration of recombinant IL-33 to WT and Rag2(-/-) mice lacking T and B cells triggered TJ disruption, whereas Rag2(-/-)Il2rg(-/-) and Rora(sg/sg) BMT mice that lack ILC2s did not show any barrier leakiness. Direct nasal administration of IL-13 was sufficient to induce deficiency in TJ barrier in bronchial epithelium of mice in vivo.
CONCLUSION: These data highlight an essential mechanism in asthma pathogenesis by demonstrating that ILC2s are responsible for bronchial epithelial TJ barrier leakiness via IL-13.

PMID: 28392332 [PubMed - as supplied by publisher]




Maternal Phthalate Exposure Promotes Allergic Airway Inflammation over Two Generations Via Epigenetic Modifications.
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Maternal Phthalate Exposure Promotes Allergic Airway Inflammation over Two Generations Via Epigenetic Modifications.

J Allergy Clin Immunol. 2017 Apr 06;:

Authors: Jahreis S, Trump S, Bauer M, Bauer T, Thürmann L, Feltens R, Wang Q, Gu L, Grützmann K, Röder S, Averbeck M, Weichenhan D, Plass C, Sack U, Borte M, Dubourg V, Schüürmann G, Simon JC, von Bergen M, Hackermüller J, Eils R, Lehmann I, Polte T

Abstract
BACKGROUND: Prenatal and early postnatal exposures to environmental factors are considered responsible for the increasing prevalence of allergic diseases. Although there is some evidence for allergy-promoting effects in children due to exposure to plasticizers like phthalates, findings of previous studies are inconsistent and lack mechanistic information.
OBJECTIVE: We investigated the effect of maternal phthalate exposure on asthma development in the subsequent generations and their underlying mechanisms including epigenetic alterations.
METHODS: Phthalate metabolites were measured within the prospective mother-child cohort LINA and correlated with asthma development in the children. A murine trans-generational asthma model was used to identify involved pathways.
RESULTS: In LINA maternal urinary concentrations of mono-n-butyl phthalate, a metabolite of butyl benzyl phthalate (BBP), were associated with an increased asthma risk in the children. Using a murine trans-generational asthma model, we demonstrate a direct effect of BBP on asthma severity in the offspring with a persistently increased airway inflammation up to the F2 generation. This disease-promoting effect was mediated by a BBP-induced global DNA hypermethylation in CD4(+) T cells of the offspring as treatment with a DNA demethylating agent alleviated exacerbation of allergic airway inflammation. 13 transcriptionally down-regulated genes linked to promoter or enhancer hypermethylation were identified. Among these, the GATA-3 repressor Zfpm1 emerged as a potential mediator of the enhanced susceptibility for Th2-driven allergic asthma.
CONCLUSION: These data provide strong evidence that maternal BBP exposure increases the risk for allergic airway inflammation in the offspring by modulating the expression of genes involved in Th2 differentiation via epigenetic alterations.

PMID: 28392331 [PubMed - as supplied by publisher]




Viral Reactivations and Associated Outcomes in Context of Immune Reconstitution after Pediatric Hematopoietic Cell Transplantation.
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Viral Reactivations and Associated Outcomes in Context of Immune Reconstitution after Pediatric Hematopoietic Cell Transplantation.

J Allergy Clin Immunol. 2017 Apr 06;:

Authors: Admiraal R, de Koning C, Lindemans CA, Bierings MB, Wensing AM, Versluys AB, Wolfs TF, Nierkens S, Boelens JJ

Abstract
BACKGROUND: Viral reactivations (VR) following hematopoietic cell transplantation (HCT) contribute to significant morbidity and mortality. Timely immune reconstitution (IR) is suggested to prevent VR.
OBJECTIVES: We studied the relation between IR (as a continuous over-time-predictor) and VR (as time-varying-predictor), and the relation between VR and other clinical outcomes.
METHODS: In this retrospective analysis, all patients receiving a first HCT between January-2004 and September-2014 were included. IR (CD3/CD4/CD8 T-cells, NK- and B-cells) was measured bi-weekly until 12 weeks, and monthly thereafter. Main outcomes of interest were VR of adenovirus (AdV), Epstein-Barr-virus (EBV), human-herpesvirus 6 (HHV6), cytomegalovirus (CMV), and BK-virus, screened weekly. Clinical outcomes included overall-survival (OS), event-free-survival, non-relapse-mortality (NRM), and graft-versus-host-disease (GvHD). Cox-proportional-hazard- and Fine-Gray-competing-risk-models were used.
RESULTS: 273 patients (0.1-22.7 years; median follow-up 58 months) were included. Delayed CD4-reconstitution predicted reactivation of AdV (HR 0.995; p=0.022), EBV (HR 0.994, p=0.029), and HHV6 (HR 0.991, p=0.012), but not CMV (p=0.31) and BK (p=0.27). Duration of AdV-reactivation was shorter with timely CD4-reconstitution, defined as ≥50*10(6) cells/L within 100-days. AdV-reactivation predicted lower OS (HR 2.17, p=0.0039) and higher NRM (HR 2.96, p=0.0008). Concomitant CD4-reconstitution abolished this negative effect of AdV-reactivation: OS (p=0.67) and NRM (p=0.64). EBV- and HHV6-reactivations were predictors for occurrence of GvHD, while CMV- and BK-reactivations did not predict clinical outcomes.
CONCLUSION: These results stress the importance of timely CD4-reconstitution. Strategies to improve CD4-reconstitution may improve HCT-outcomes, including survival, and reduce the need for toxic anti-viral therapies.

PMID: 28392330 [PubMed - as supplied by publisher]




Interplay Between the Skin Barrier and Immune Cells in Patients with Atopic Dermatitis Unraveled by Means of Mathematical Modeling.
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Interplay Between the Skin Barrier and Immune Cells in Patients with Atopic Dermatitis Unraveled by Means of Mathematical Modeling.

J Allergy Clin Immunol. 2017 Apr 06;:

Authors: Bending D, Ono M

PMID: 28392329 [PubMed - as supplied by publisher]




Basophil-derived interleukin-4 promotes epicutaneous antigen sensitization concomitant with the development of food allergy.
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Basophil-derived interleukin-4 promotes epicutaneous antigen sensitization concomitant with the development of food allergy.

J Allergy Clin Immunol. 2017 Apr 05;:

Authors: Hussain M, Borcard L, Walsh KP, Pena Rodriguez M, Mueller C, Kim BS, Kubo M, Artis D, Noti M

Abstract
BACKGROUND: Exaggerated TSLP production and infiltration of basophils are associated with the pathogenesis of atopic dermatitis (AD), a recognized risk factor for the development of food allergies. While TSLP and basophils have been implicated to promote food-induced allergic disorders in response to epicutaneous sensitization, the mechanisms by which TSLP-elicited basophils guide the progression of allergic inflammation in the skin to distant mucosal sites such as the gastrointestinal tract are poorly understood.
OBJECTIVE: We sought to test the role of basophil-intrinsic IL-4 production in TH2 sensitization to food antigens in the skin and effector food allergic responses in the gut.
METHODS: Mice were epicutaneously sensitized with ovalbumin on an AD-like skin lesion, followed by intra-gastric antigen challenge to induce IgE-mediated food allergy. The requirement for basophil-derived IL-4 production for TH2 polarization and the pathogenesis of IgE-mediated food allergy was assessed in vitro by co-culture experiments with naïve T cells and in vivo using IL-4 3'UTR mice that selectively lack IL-4 production in basophils.
RESULTS: Epicutaneous food antigen sensitization is associated with the infiltration of IL-4 competent innate immune cells to the skin with basophils and eosinophils representing the predominant populations. In contrast to basophils, absence of eosinophils did not alter disease outcome. Co-culture of IL-4 competent basophils together with dendritic cells and naïve T cells was sufficient to promote TH2 polarization in an IL-4 dependent manner in vitro, while absence of basophil-intrinsic IL-4 production in vivo was associated with reduced food allergic responses.
CONCLUSION: TSLP-elicited basophils promote epicutaneous sensitization to food antigens and subsequent IgE-mediated food allergy via IL-4. Strategies to target the TSLP-basophil-IL4 axis in patients with AD may lead to innovative therapies that can prevent the progression of allergies to distant mucosal sites.

PMID: 28390860 [PubMed - as supplied by publisher]




Functional relevance of microbiome signatures: The correlation era requires tools for consolidation.
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Functional relevance of microbiome signatures: The correlation era requires tools for consolidation.

J Allergy Clin Immunol. 2017 Apr;139(4):1092-1098

Authors: Buttó LF, Haller D

Abstract
Compelling research over the past decade identified a fundamental role of the intestinal microbiome on human health. Compositional and functional changes of this microbial ecosystem are correlated with a variety of human pathologies. Metagenomic resolution and bioinformatic tools considerably improved, allowing even strain-level analysis. However, the search for microbial risk patterns in human cohorts is often confounded by environmental factors (eg, medication) and host status (eg, disease relapse), questioning the prognostic and therapeutic value of the currently available information. In addition to a better stratification of human phenotypes, the implementation of standardized protocols for sampling and analysis is needed to improve the reproducibility and comparability of microbiome signatures at a meaningful taxonomic resolution. At the level of mechanistic understanding, the molecular integration of pleiotropic signals coming from this complex and dynamically changing ecosystem is one of the biggest challenges in this field. The first successful attempts to apply reverse genetics based on the available metagenomic information yielded identification of small molecules and metabolites with functional relevance for microbe-host interactions. Further expansion on the isolation of bacteria from the "unculturable biomass" will help characterize microbiome signatures in model systems, finally aiming at the development of clinically relevant synthetic consortia with safe and functionally well-defined strains. In conclusion and beyond reasonable enthusiasm, the mechanistic implementation and clinical relevance of microbiome alterations on disease susceptibility is still in its infancy, but the integration of all the above-mentioned strategies will help overcome the correlation era in microbiome research and lead to a rational evaluation of clinical strategies relevant for targeted microbial intervention.

PMID: 28390576 [PubMed - in process]




Correlation between early-life regulation of the immune system by microbiota and allergy development.
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Correlation between early-life regulation of the immune system by microbiota and allergy development.

J Allergy Clin Immunol. 2017 Apr;139(4):1084-1091

Authors: Gensollen T, Blumberg RS

Abstract
Early postnatal life is a key time for development of the immune system and colonization of the host by microbiota. Recent studies have shown that specific limbs of the immune system can be regulated by microbiota in a time-restricted period during early life. Studies in mouse models have shown that perturbations of the microbiota during early life can cause immune effects that can persist into adulthood and create increased host susceptibility to certain diseases. Here we discuss the role of early-life regulation of the immune system by the microbiota and how it can be related to allergy development.

PMID: 28390575 [PubMed - in process]




Airway microbial dysbiosis in asthmatic patients: A target for prevention and treatment?
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Airway microbial dysbiosis in asthmatic patients: A target for prevention and treatment?

J Allergy Clin Immunol. 2017 Apr;139(4):1071-1081

Authors: Chung KF

Abstract
There has been long-standing interest in the role of bacterial communities in the complex and heterogeneous disease of asthma. With the advent of 16s rRNA sequencing replacing traditional culture methods, a strong association between the presence of bacterial communities with asthma has emerged. These microbiota can be modulated by various environmental factors, including diet, antibiotics, and early-life microbial exposures. Microbiota in the gut and lungs can influence both the inception and progress of asthma. In babies and infants the presence of pathogenic bacteria in the lungs and gut has been associated with subsequent development of allergic sensitization and asthma. Lung microbiota are present in the airways of healthy subjects but are dysregulated in adults with asthma, with a reduced diversity and community composition that has been linked to severity and inflammatory phenotypes. Causality between certain gut microbiota and the development of allergic asthma has been shown in experiments conducted in neonatal mice. Manipulation of the airway microbiome, particularly in early life, might be a strategy to prevent or treat asthma, although the results of studies of probiotics used together with prebiotics have been overall negative. A better understanding of the regulation of both the lung and gut microbiota to derive appropriate targets for prevention or treatment of asthma is needed.

PMID: 28390574 [PubMed - in process]




The immunology of atopic dermatitis and its reversibility with broad-spectrum and targeted therapies.
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The immunology of atopic dermatitis and its reversibility with broad-spectrum and targeted therapies.

J Allergy Clin Immunol. 2017 Apr;139(4S):S65-S76

Authors: Brunner PM, Guttman-Yassky E, Leung DY

Abstract
Atopic dermatitis (AD), the most common chronic inflammatory skin disease, is driven by both terminal keratinocyte differentiation defects and strong type 2 immune responses. In contrast to chronic plaque-type psoriasis, AD is now understood to be a much more heterogeneous disease, with additional activation of TH22, TH17/IL-23, and TH1 cytokine pathways depending on the subtype of the disease. In this review we discuss our current understanding of the AD immune map in both patients with early-onset and those with chronic disease. Clinical studies with broad and targeted therapeutics have helped to elucidate the contribution of various immune axes to the disease phenotype. Importantly, immune activation extends well beyond lesional AD because nonlesional skin and the blood component harbor AD-specific inflammatory changes. For this reason, future therapeutics will need to focus on a systemic treatment approach, especially in patients with moderate-to-severe disease.

PMID: 28390479 [PubMed - in process]




Clinical phenotypes and endophenotypes of atopic dermatitis: Where are we, and where should we go?
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Clinical phenotypes and endophenotypes of atopic dermatitis: Where are we, and where should we go?

J Allergy Clin Immunol. 2017 Apr;139(4S):S58-S64

Authors: Bieber T, D'Erme AM, Akdis CA, Traidl-Hoffmann C, Lauener R, Schäppi G, Schmid-Grendelmeier P

Abstract
Atopic dermatitis (AD) is a paradigmatic chronic inflammatory skin disease characterized by a complex pathophysiology and a wide spectrum of the clinical phenotype. Despite this high degree of heterogeneity, AD is still considered a single disease and usually treated according to the "one-size-fits-all" approach. Thus more tailored prevention and therapeutic strategies are still lacking. As for other disciplines, such as oncology or rheumatology, we have to approach AD in a more differentiated way (ie, to dissect and stratify the complex clinical phenotype into more homogeneous subgroups based on the endophenotype [panel of biomarkers]) with the aim to refine the management of this condition. Because we are now entering the era of personalized medicine, a systems biology approach merging the numerous clinical phenotypes with robust (ie, relevant and validated) biomarkers will be needed to best exploit their potential significance for the future molecular taxonomy of AD. This approach will not only allow an optimized prevention and treatment with the available drugs but also hopefully help assign newly developed medicinal products to those patients who will have the best benefit/risk ratio.

PMID: 28390478 [PubMed - in process]




Current guidelines for the evaluation and management of atopic dermatitis: A comparison of the Joint Task Force Practice Parameter and American Academy of Dermatology guidelines.
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Current guidelines for the evaluation and management of atopic dermatitis: A comparison of the Joint Task Force Practice Parameter and American Academy of Dermatology guidelines.

J Allergy Clin Immunol. 2017 Apr;139(4S):S49-S57

Authors: Eichenfield LF, Ahluwalia J, Waldman A, Borok J, Udkoff J, Boguniewicz M

Abstract
Atopic dermatitis (AD) is a chronic pruritic inflammatory disease that commonly presents in the pediatric population. Although definitions and diagnosis of AD have largely been agreed upon, allergists and dermatologists have similar and divergent approaches to the management of AD. This review facilitated integration of the American Academy of Allergy, Asthma & Immunology/American College of Allergy, Asthma & Immunology Joint Task Force 2012 AD Practice Parameter and the 2014 American Academy of Dermatology guidelines to highlight the basic principles of AD management and discuss therapies and management of AD from the distinct perspectives of the allergist and dermatologist.

PMID: 28390477 [PubMed - in process]




Assessing the current treatment of atopic dermatitis: Unmet needs.
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Assessing the current treatment of atopic dermatitis: Unmet needs.

J Allergy Clin Immunol. 2017 Apr;139(4S):S47-S48

Authors: Leung DY, Guttman-Yassky E

PMID: 28390476 [PubMed - in process]




Omalizumab is Effective in Cold Urticaria - Results of a Randomized, Placebo Controlled Trial.
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Omalizumab is Effective in Cold Urticaria - Results of a Randomized, Placebo Controlled Trial.

J Allergy Clin Immunol. 2017 Apr 04;:

Authors: Metz M, Schütz A, Weller K, Gorczyza M, Zimmer S, Staubach P, Merk HF, Maurer M

PMID: 28389393 [PubMed - as supplied by publisher]




IL-10 Overexpression Predisposes to Invasive Aspergillosis by Suppressing Antifungal Immunity.
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IL-10 Overexpression Predisposes to Invasive Aspergillosis by Suppressing Antifungal Immunity.

J Allergy Clin Immunol. 2017 Apr 04;:

Authors: Cunha C, Gonçalves SM, Duarte-Oliveira C, Leite L, Lagrou K, Marques A, Lupiañez CB, Mesquita I, Gaifem J, Barbosa AM, Pinho Vaz C, Branca R, Campilho F, Freitas F, Ligeiro D, Lass-Flörl C, Löffler J, Jurado M, Saraiva M, Kurzai O, Rodrigues F, Castro AG, Silvestre R, Sainz J, Maertens JA, Torrado E, Jacobsen ID, Lacerda JF, Campos A, Carvalho A

Abstract
We show that the genetically-determined overexpression of IL-10 is a risk factor for invasive aspergillosis after stem-cell transplantation. Our results identify an IL-10-mediated mechanism that regulates the balance between anti- and proinflammatory antifungal immunity.

PMID: 28389392 [PubMed - as supplied by publisher]




Omalizumab is Effective in Symptomatic Dermographism - results of a Randomized, Placebo Controlled Trial.
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Omalizumab is Effective in Symptomatic Dermographism - results of a Randomized, Placebo Controlled Trial.

J Allergy Clin Immunol. 2017 Apr 04;:

Authors: Maurer M, Schütz A, Weller K, Schoepke N, Peveling-Oberhag A, Staubach P, Müller S, Jakob T, Metz M

PMID: 28389391 [PubMed - as supplied by publisher]




Ibrutinib, a BTK inhibitor used for treatment of lymphoproliferative disorders, eliminates both aeroallergen skin test and basophil activation test reactivity.
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Ibrutinib, a BTK inhibitor used for treatment of lymphoproliferative disorders, eliminates both aeroallergen skin test and basophil activation test reactivity.

J Allergy Clin Immunol. 2017 Apr 04;:

Authors: Regan JA, Cao Y, Dispenza MC, Ma S, Gordon LI, Petrich AM, Bochner BS

Abstract
Ibrutinib, a Bruton's tyrosine kinase (BTK) inhibitor, was shown to eliminate skin test reactivity in vivo and IgE-dependent basophil activation testing ex vivo. Blockade of the BTK pathway may represent a novel therapeutic strategy for the effective reduction of allergic reactivity.

PMID: 28389390 [PubMed - as supplied by publisher]




Enhanced Chemosensory Sensitivity in Idiopathic Rhinitis Patients and its Reversal by Nasal Capsaicin Treatment.
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Enhanced Chemosensory Sensitivity in Idiopathic Rhinitis Patients and its Reversal by Nasal Capsaicin Treatment.

J Allergy Clin Immunol. 2017 Apr 04;:

Authors: Van Gerven L, Alpizar YA, Steelant B, Callebaut I, Kortekaas Krohn I, Wouters M, Vermeulen F, Boeckxstaens G, Talavera K, Hellings PW

Abstract
We show electrophysiological evidence for an increased chemical sensitivity in idiopathic rhinitis patients compared to healthy controls. This abnormality is decreased after capsaicin treatment, along with a reduction of symptoms.

PMID: 28389389 [PubMed - as supplied by publisher]