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Human newborn B cells mount an IFNAR-dependent humoral response to RSV.
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Human newborn B cells mount an IFNAR-dependent humoral response to RSV.

J Allergy Clin Immunol. 2016 Dec 05;:

Authors: Jans J, Pettengill M, Kim D, van der Made C, de Groot R, Henriet S, de Jonge MI, Ferwerda G, Levy O

Abstract
This study provides evidence of a first line of human humoral defense against RSV infection in early life including the presence of natural neutralizing anti-RSV IgM as well as an IFN-β-mediated newborn B cell activation.

PMID: 27931976 [PubMed - as supplied by publisher]




Identification of IL-17F/frequent exacerbator endotype in asthma.
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Identification of IL-17F/frequent exacerbator endotype in asthma.

J Allergy Clin Immunol. 2016 Dec 05;:

Authors: Ricciardolo FL, Sorbello V, Folino A, Gallo F, Massaglia GM, Favatà G, Conticello S, Vallese D, Gani F, Malerba M, Folkerts G, Rolla G, Profita M, Mauad T, Di Stefano A, Ciprandi G

Abstract
BACKGROUND: Severe asthma might be associated with neutrophil recruitment and Th17 cytokines over-expression in bronchial biopsies.
OBJECTIVE: To study IL-17-related cytokines in nasal/bronchial biopsies from controls and mild (MA)-to-severe (SA) asthmatics in relation to exacerbation rate.
METHODS: Inflammatory cells and IL-17A(+), IL-17F(+), IL-21(+), IL-22(+) and IL-23(+) cells were examined by immunohistochemistry (IHC) in cryostat sections of bronchial/nasal biopsies obtained from 33 SA (21 frequent exacerbators (FE)), 31 MA (3 FE) and 14 controls. IL-17F protein was also measured by ELISA in bronchial/nasal lysates and by IHC in bronchial tissue obtained from subjects died for fatal asthma. Immunofluorescence/confocal microscopy was used for IL-17F co-localization.
RESULTS: Higher number (p<0.05) of neutrophils, IL-17A(+), IL-17F(+) and IL-21(+) cells in bronchial biopsies and higher number (p<0.01) of IL-17F(+) and IL-21(+) cells in nasal biopsies were observed in SA compared to MA. Bronchial IL-17F(+) cells correlated with bronchial neutrophils (r=0.54), exacerbation rate (r=0.41) and FEV1 (r=-0.46). Nasal IL-17F(+) cells correlated with bronchial IL-17F (r=0.35), exacerbation rate (r=0.47) and FEV1 (r=-0.61). FE showed increased number of bronchial neutrophils/eosinophils/CD4(+)/CD8(+) cells and bronchial/nasal IL-17F(+) cells. ROC curve analysis evidenced predictive cut-off values of bronchial neutrophils and nasal/bronchial IL-17F for discriminating between asthmatics and controls, between MA and SA and between FE and non-FE. IL-17F protein increased in bronchial/nasal lysates of SA and FE and in bronchial tissue of fatal asthma. IL-17F co-localized in CD4(+)/CD8(+) cells.
CONCLUSIONS: IL-17-related cytokines expression was amplified in bronchial/nasal mucosa of neutrophilic asthma prone to exacerbation suggesting a pathogenic role of IL-17F in frequent exacerbators.

PMID: 27931975 [PubMed - as supplied by publisher]




Mathematical Modeling of Atopic Dermatitis Reveals "Double switch" Mechanisms Underlying Four Common Disease Phenotypes.
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Mathematical Modeling of Atopic Dermatitis Reveals "Double switch" Mechanisms Underlying Four Common Disease Phenotypes.

J Allergy Clin Immunol. 2016 Dec 05;:

Authors: Domínguez-Hüttinger E, Christodoulides P, Miyauchi K, Irvine AD, Okada-Hatakeyama M, Kubo M, Tanaka RJ

Abstract
BACKGROUND: The skin barrier acts as the first line of defense against constant exposure to biological, microbial, physical and chemical environmental stressors. Dynamic interplay between defects in the skin barrier, dysfunctional immune responses, and environmental stressors are major factors in the development of atopic dermatitis (AD). A systems-biology modeling approach can yield significant insights into these complex and dynamic processes through integration of prior biological data.
OBJECTIVE: To develop a multi-scale mathematical model of AD pathogenesis that describes the dynamic interplay between the skin barrier, environmental stress and immune dysregulation, and use it to achieve a coherent mechanistic understanding of onset, progression and prevention of AD.
METHODS: We mathematically investigated synergistic effects of known genetic and environmental risk factors on the dynamic onset and progression of the AD phenotype, from a mostly asymptomatic mild phenotype to a severe treatment-resistant form.
RESULTS: Our model analysis identified a "double switch", with two concatenated bistable switches, as a key network motif that dictates AD pathogenesis: The first switch is responsible for the reversible onset of inflammation; The second switch is triggered by long-lasting or frequent activation of the first switch, causing the irreversible onset of systemic Th2 sensitization and worsening of AD symptoms.
CONCLUSIONS: Our mathematical analysis of the bistable switch predicts that genetic risk factors lower the threshold of environmental stressors to trigger systemic Th2 sensitization. This analysis predicts and explains four common clinical AD phenotypes from a mild and reversible phenotype through to severe and recalcitrant disease and provides a mechanistic explanation for clinically-demonstrated preventive effects of emollient treatments against development of AD.

PMID: 27931974 [PubMed - as supplied by publisher]




Effect of probiotics in prevention of atopic dermatitis is dependent on the intrinsic microbiota at early infancy.
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Effect of probiotics in prevention of atopic dermatitis is dependent on the intrinsic microbiota at early infancy.

J Allergy Clin Immunol. 2016 Dec 05;:

Authors: Avershina E, Cabrera-Rubio R, Lundgård K, Perez-Martinez G, Collado MC, Storrø O, Øien T, Dotterud CK, Johnsen R, Rudi K

Abstract
Although a link between probiotic intervention and reduction in atopic disease has been documented, no consistent associations with microbiota has yet been established. Here we have conducted an extensive analysis of the microbiota from more than 250 mother child pairs from a probiotic intervention cohort, where we previously have shown 40 % reduction in atopic dermatitis. Within the probiotic intervention group at the age of 10 days we found that the atopic children had a deviating microbiota (p = 0.028, BH-FDR corrected Kruskal Wallis) with high levels (> 10 %) of a bacterium related to Bifidobacterium dentium (p=0.039, BH-FDR corrected Chi-square). Based on these findings, we propose a model with two groups of children where the group responding to probiotic intervention, has gut microbiota related to that of non-atopic children; while the non-responding group has a divergent microbiota at the age of 10 days with overrepresented amounts of B. dentium. In conclusion, our results support the importance of early colonization for prevention of diseases developing later in life, with potential intervention effects being dependent on the intrinsic microbiota.

PMID: 27931973 [PubMed - as supplied by publisher]




Liver transplantation in patients with primary antibody deficiency.
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Liver transplantation in patients with primary antibody deficiency.

J Allergy Clin Immunol. 2016 Dec 05;:

Authors: Jørgensen SF, Macpherson ME, Bjøro K, Karlsen TH, Reims HM, Grzyb K, Fosby B, Fevang B, Aukrust P, Nordøy I

Abstract
Patients with primary antibody deficiency and liver failure should be considered for liver transplantation and not rejected because of their immunodeficiency alone. Improved anti-fungal prophylaxis may further improve their prognosis.

PMID: 27931972 [PubMed - as supplied by publisher]




The Editors' Choice.
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The Editors' Choice.

J Allergy Clin Immunol. 2016 Dec;138(6):1559-1560

Authors: Akdis CA, Ballas ZK, Associate Editors of the JACI

PMID: 27931537 [PubMed - in process]




Advances in atopic dermatitis in 2015.
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Advances in atopic dermatitis in 2015.

J Allergy Clin Immunol. 2016 Dec;138(6):1548-1555

Authors: Nomura T, Kabashima K

Abstract
This review aims to highlight recently published articles on atopic dermatitis (AD). Updated are the insights into epidemiology, pathology, diagnostics, and therapy. Epidemiologic studies have revealed a positive correlation between AD and systemic conditions, such as rheumatoid arthritis, inflammatory bowel disease, and neonatal adiposity. Pathologic findings highlight the involvement of novel barrier factors (desmoplakin and claudin), novel immune cell subsets (pathogenic effector TH2 cells and group 2 innate lymphoid cells), and differential skewing of helper T cells (eg, TH17 dominance in Asians with AD). As diagnostics, noninvasive examinations of the transepidermal water loss of neonates, the density of epidermal Staphylococcus species, and the gut flora might prognosticate the onset of AD. As for therapy, various methods are proposed, including conventional (petrolatum and UV) and molecule-oriented regimens targeting Janus kinase, signal transducer and activator of transcription 3, extracellular signal-regulated kinase, sirtuin 1, or aryl hydrocarbon receptor.

PMID: 27931536 [PubMed - in process]




Advances in food allergy in 2015.
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Advances in food allergy in 2015.

J Allergy Clin Immunol. 2016 Dec;138(6):1541-1547

Authors: Wood RA

Abstract
This review highlights research advances in food allergy that were published in the Journal in 2015. The world of food allergy research continues to rapidly accelerate, with increasing numbers of outstanding submissions to the Journal. In 2015, important studies on the epidemiology of food allergy were published, suggesting differential rates of food allergy in specific racial and ethnic groups. Even more importantly, studies were published identifying specific risk factors for the development of peanut allergy, as well as specific prevention strategies. We also saw new studies on the diagnosis of food allergy and potential approaches to the treatment of food allergy, as well as novel mechanistic studies helping to explain the immunologic correlates of food allergy and food desensitization.

PMID: 27931535 [PubMed - in process]




Advances in clinical immunology in 2015.
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Advances in clinical immunology in 2015.

J Allergy Clin Immunol. 2016 Dec;138(6):1531-1540

Authors: Chinen J, Notarangelo LD, Shearer WT

Abstract
Advances in clinical immunology in the past year included the report of practice parameters for the diagnosis and management of primary immunodeficiencies to guide the clinician in the approach to these relatively uncommon disorders. We have learned of new gene defects causing immunodeficiency and of new phenotypes expanding the spectrum of conditions caused by genetic mutations such as a specific regulator of telomere elongation (RTEL1) mutation causing isolated natural killer cell deficiency and mutations in ras-associated RAB (RAB27) resulting in immunodeficiency without albinism. Advances in diagnosis included the increasing use of whole-exome sequencing to identify gene defects and the measurement of serum free light chains to identify secondary hypogammaglobulinemias. For several primary immunodeficiencies, improved outcomes have been reported after definitive therapy with hematopoietic stem cell transplantation and gene therapy.

PMID: 27931534 [PubMed - in process]




Care transition interventions for children with asthma in the emergency department.
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Care transition interventions for children with asthma in the emergency department.

J Allergy Clin Immunol. 2016 Dec;138(6):1518-1525

Authors: Martin MA, Press VG, Nyenhuis SM, Krishnan JA, Erwin K, Mosnaim G, Margellos-Anast H, Paik SM, Ignoffo S, McDermott M, CHICAGO Plan Consortium

Abstract
The emergency department (ED) is a critical point of identification and treatment for some of the most high-risk children with asthma. This review summarizes the evidence regarding care transition interventions originating in the ED for children with uncontrolled asthma, with a focus on care coordination and self-management education. Although many interventions on care transition for pediatric asthma have been tested, only a few were actually conducted in the ED setting. Most of these targeted both care coordination and self-management education but ultimately did not improve attendance at follow-up appointments with primary care providers, improve asthma control, or reduce health care utilization. Conducting any ED-based intervention in the current environment is challenging because of the many demands on ED providers and staff, poor communication within and outside of the medical sector, and caregiver/patient burden. The evidence to date suggests that ED care transition interventions should consider expanding beyond the ED to bridge the multiple sectors children with asthma navigate, including health care settings, homes, schools, and community spaces. Patient-centered approaches may also be important to ensure adequate intervention design, enrollment, retention, and evaluation of outcomes important to children and their families.

PMID: 27931533 [PubMed - in process]




Patient-centered outcomes research to improve asthma outcomes.
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Patient-centered outcomes research to improve asthma outcomes.

J Allergy Clin Immunol. 2016 Dec;138(6):1503-1510

Authors: Anise A, Hasnain-Wynia R

Abstract
The Patient-Centered Outcomes Research Institute is funding 8 comparative effectiveness research projects to improve patient-centered outcomes for African American and Hispanic/Latino patients with uncontrolled asthma. These projects aim to compare multilevel interventions with known efficacy at the community, home, and health system levels to enhance patient and clinician uptake of the National Heart, Lung, and Blood Institute's National Asthma Education Prevention Program guidelines and improve outcomes. The National Asthma Education Prevention Program guidelines provide clinicians with a range of acceptable approaches for the diagnosis and management of asthma and define general practices that meet the needs of most patients. Yet disparities in asthma care and outcomes remain pervasive for African Americans and Hispanics/Latinos. The National Heart, Lung, and Blood Institute AsthmaNet consortium has identified several top research priorities for pediatric and adult populations, including a recommendation to examine tailored approaches based on race/ethnicity. In addition, the guidelines emphasize the need for studies that focus on multicomponent interventions recognizing that single interventions are generally ineffective. This article will describe the Patient-Centered Outcomes Research Institute-funded asthma projects and how they are individually and collectively addressing evidence gaps in asthma care by focusing on multicomponent and tailored approaches for improving outcomes and reducing disparities for African American and Hispanic/Latino patients.

PMID: 27931532 [PubMed - in process]




Rapamycin Preferentially Inhibits Human IL-5(+) Th2 Cell Proliferation via an mTORC1/S6 Kinase-1 Dependent Pathway.
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Rapamycin Preferentially Inhibits Human IL-5(+) Th2 Cell Proliferation via an mTORC1/S6 Kinase-1 Dependent Pathway.

J Allergy Clin Immunol. 2016 Dec 03;:

Authors: Yin Y, Mitson-Salazar A, Wansley DL, Singh SP, Prussin C

PMID: 27923564 [PubMed - as supplied by publisher]




Association between the CDHR3 rs6967330 risk allele and chronic rhinosinusitis.
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Association between the CDHR3 rs6967330 risk allele and chronic rhinosinusitis.

J Allergy Clin Immunol. 2016 Dec 03;:

Authors: Chang EH, Willis AL, McCrary HC, Noutsious GT, Le CH, Chiu AG, Mansfield CJ, Reed DR, Brooks SG, Adappa ND, Palmer JN, Cohen NG, Stern DA, Guerra S, Martinez FD

Abstract
A retrospective, multi-center study of adults with and without chronic rhinosinusitis (CRS) identifies a significant association between rs6967330 in the viral receptor CDHR3 - known to be associated with wheezing and asthma in children - and the development of CRS.

PMID: 27923563 [PubMed - as supplied by publisher]




Molecular engineering of a therapeutic antibody for Blo t 5-induced allergic asthma.
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Molecular engineering of a therapeutic antibody for Blo t 5-induced allergic asthma.

J Allergy Clin Immunol. 2016 Dec 03;:

Authors: Chan JH, Chua YL, Peh HY, Jovanovic V, Gascoigne NR, Wong WS, Chew FT, Hanson BJ, Kemeny DM, MacAry PA

PMID: 27923562 [PubMed - as supplied by publisher]




FcεRI cross-linking reduces cord blood dendritic cell responsiveness to lipopolysaccharides.
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FcεRI cross-linking reduces cord blood dendritic cell responsiveness to lipopolysaccharides.

J Allergy Clin Immunol. 2016 Dec 02;:

Authors: Paveglio S, Bennett E, Hawley KL, Matson AP

Abstract
Anti-FcεRI stimulation was found to reduce the responsiveness of cord blood mDCs to lipopolysaccharides, thus supporting the growing body of evidence that DCs can play a regulatory role in the setting of IgE-mediated inflammation.

PMID: 27919739 [PubMed - as supplied by publisher]




Peanut oral immunotherapy decreases IgE to Ara h 2 and Ara h 6 but does not enhance sensitization to cross-reactive allergens.
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Peanut oral immunotherapy decreases IgE to Ara h 2 and Ara h 6 but does not enhance sensitization to cross-reactive allergens.

J Allergy Clin Immunol. 2016 Dec 01;:

Authors: Uotila R, Kukkonen AK, Greco D, Pelkonen AS, Mäkelä MJ

Abstract
During peanut OIT, the serological response is directed to the peanut storage proteins, especially, to the 2S albumins. No neosensitization to cross-reactive allergens emerges.

PMID: 27916627 [PubMed - as supplied by publisher]