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Article ; Online: Increased duration of pollen and mold exposure are linked to climate change

Bibek Paudel / Theodore Chu / Meng Chen / Vanitha Sampath / Mary Prunicki / Kari C. Nadeau

Scientific Reports, Vol 11, Iss 1, Pp 1-

2021 Volume 12

Abstract: Abstract Pollen and molds are environmental allergens that are affected by climate change. As pollen and molds exhibit geographical variations, we sought to understand the impact of climate change (temperature, carbon dioxide (CO2), precipitation, smoke ... ...

Abstract	Abstract Pollen and molds are environmental allergens that are affected by climate change. As pollen and molds exhibit geographical variations, we sought to understand the impact of climate change (temperature, carbon dioxide (CO2), precipitation, smoke exposure) on common pollen and molds in the San Francisco Bay Area, one of the largest urban areas in the United States. When using time-series regression models between 2002 and 2019, the annual average number of weeks with pollen concentrations higher than zero increased over time. For tree pollens, the average increase in this duration was 0.47 weeks and 0.51 weeks for mold spores. Associations between mold, pollen and meteorological data (e.g., precipitation, temperature, atmospheric CO2, and area covered by wildfire smoke) were analyzed using the autoregressive integrated moving average model. We found that peak concentrations of weed and tree pollens were positively associated with temperature (p < 0.05 at lag 0–1, 0–4, and 0–12 weeks) and precipitation (p < 0.05 at lag 0–4, 0–12, and 0–24 weeks) changes, respectively. We did not find clear associations between pollen concentrations and CO2 levels or wildfire smoke exposure. This study’s findings suggest that spore and pollen activities are related to changes in observed climate change variables.
Keywords	Medicine ; R ; Science ; Q
Subject code	333
Language	English
Publishing date	2021-06-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Cytometric analysis reveals an association between allergen-responsive natural killer cells and human peanut allergy

Xiaoying Zhou / Wong Yu / Diane M. Dunham / Jackson P. Schuetz / Catherine A. Blish / Rosemarie H. DeKruyff / Kari C. Nadeau

The Journal of Clinical Investigation, Vol 132, Iss

2022 Volume 20

Abstract: Food allergies are a leading cause of anaphylaxis, and allergen-specific immune responses in both the innate and the adaptive immune system play key roles in its pathogenesis. We conducted a comprehensive phenotypic and functional investigation of immune ...

Abstract	Food allergies are a leading cause of anaphylaxis, and allergen-specific immune responses in both the innate and the adaptive immune system play key roles in its pathogenesis. We conducted a comprehensive phenotypic and functional investigation of immune cell responses from nonallergic (NA) and peanut allergic (PA) participants cultured with media alone or peanut protein and found, surprisingly, that NK cell activation was strongly associated with the immune response to allergen in PA participants. Peanut-responsive NK cells manifested a distinct expression pattern in PA participants compared with NA participants. Allergen-activated NK cells expressed both Th2 and immune regulatory cytokines, hinting at a potential functional role in mediating and regulating the Th2 allergic response. Depletion of CD3+ T cells attenuated the response of NK cells to peanut-allergen stimulation, suggesting that peanut-responsive NK cells are T cell dependent. We also showed that oral immune therapy was associated with decreased NK responses to peanut allergen stimulation in vitro. These results demonstrate that NK cells are associated with the food-allergic immune response, and the magnitude of this mobilized cell population suggests that they play a functional role in allergic immunity.
Keywords	Immunology ; Medicine ; R
Subject code	610
Language	English
Publishing date	2022-10-01T00:00:00Z
Publisher	American Society for Clinical Investigation
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Targeted DNA methylation profiling reveals epigenetic signatures in peanut allergy

Xiaoying Zhou / Xiaorui Han / Shu-Chen Lyu / Bryan Bunning / Laurie Kost / Iris Chang / Shu Cao / Vanitha Sampath / Kari C. Nadeau

JCI Insight, Vol 6, Iss

2021 Volume 6

Abstract: DNA methylation (DNAm) has been shown to play a role in mediating food allergy; however, the mechanism by which it does so is poorly understood. In this study, we used targeted next-generation bisulfite sequencing to evaluate DNAm levels in 125 targeted ... ...

Abstract	DNA methylation (DNAm) has been shown to play a role in mediating food allergy; however, the mechanism by which it does so is poorly understood. In this study, we used targeted next-generation bisulfite sequencing to evaluate DNAm levels in 125 targeted highly informative genomic regions containing 602 CpG sites on 70 immune-related genes to understand whether DNAm can differentiate peanut allergy (PA) versus nonallergy (NA). We found PA-associated DNAm signatures associated with 12 genes (7 potentially novel to food allergy, 3 associated with Th1/Th2, and 2 associated with innate immunity), as well as DNAm signature combinations with superior diagnostic potential compared with serum peanut–specific IgE for PA versus NA. Furthermore, we found that, following peanut protein stimulation, peripheral blood mononuclear cell (PBMCs) from PA participants showed increased production of cognate cytokines compared with NA participants. The varying responses between PA and NA participants may be associated with the interaction between the modification of DNAm and the interference of environment. Using Euclidean distance analysis, we found that the distances of methylation profile comprising 12 DNAm signatures between PA and NA pairs in monozygotic (MZ) twins were smaller than those in randomly paired genetically unrelated individuals, suggesting that PA-related DNAm signatures may be associated with genetic factors.
Keywords	Genetics ; Immunology ; Medicine ; R
Subject code	616
Language	English
Publishing date	2021-03-01T00:00:00Z
Publisher	American Society for Clinical investigation
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: IL-4RÎ± Inhibitor for Atopic Disease

Chang, Howard Y / Kari C. Nadeau

Cell. 2017 July 13, v. 170

2017

Abstract: Dupilumab is a fully human IgG4 monoclonal antibody directed against the IL-4RÎ± subunit of IL-4 and IL-13 receptors. It blocks the signaling pathways of IL-4 and IL-13, key cytokines that drive type 2 inflammatory response. In March 2017, dupilumab was ... ...

Abstract	Dupilumab is a fully human IgG4 monoclonal antibody directed against the IL-4RÎ± subunit of IL-4 and IL-13 receptors. It blocks the signaling pathways of IL-4 and IL-13, key cytokines that drive type 2 inflammatory response. In March 2017, dupilumab was approved for use in the treatment of atopic dermatitis (eczema). To view this Bench to Bedside, open or download the PDF.
Keywords	atopic dermatitis ; eczema ; humans ; immunoglobulin G ; inflammation ; interleukin-13 ; interleukin-4 ; monoclonal antibodies ; receptors ; signal transduction
Language	English
Dates of publication	2017-0713
Size	p. 222.
Publishing place	Elsevier Inc.
Document type	Article
ZDB-ID	187009-9
ISSN	1097-4172 ; 0092-8674
ISSN (online)	1097-4172
ISSN	0092-8674
DOI	10.1016/j.cell.2017.06.046
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Mass cytometry analysis of blood from peanut-sensitized tolerant and clinically allergic infants

Amanda R. Tursi / Nicholas K. Saba / Diane Dunham / Monali Manohar / Rachel L. Peters / Richard Saffery / Jennifer J. Koplin / Kari C. Nadeau / Melanie R. Neeland / Sandra Andorf

Scientific Data, Vol 9, Iss 1, Pp 1-

2022 Volume 8

Abstract: Measurement(s) expression profiling Technology Type(s) cytometry time of flight assay Sample Characteristic - Organism Homo sapiens Sample Characteristic - Location ... ...

Abstract	Measurement(s) expression profiling Technology Type(s) cytometry time of flight assay Sample Characteristic - Organism Homo sapiens Sample Characteristic - Location Australia
Keywords	Science ; Q
Language	English
Publishing date	2022-12-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: An optimized protocol for phenotyping human granulocytes by mass cytometry

Nora Vivanco Gonzalez / John-Paul Oliveria / Dmitry Tebaykin / Geoffrey T. Ivison / Kaori Mukai / Mindy M. Tsai / Luciene Borges / Kari C. Nadeau / Stephen J. Galli / Albert G. Tsai / Sean C. Bendall

STAR Protocols, Vol 3, Iss 2, Pp 101280- (2022)

2022

Abstract: Summary: Granulocytes encompass diverse roles, from fighting off pathogens to regulating inflammatory processes in allergies. These roles are represented by distinct cellular phenotypes that we captured with mass cytometry (CyTOF). Our protocol enables ... ...

Abstract	Summary: Granulocytes encompass diverse roles, from fighting off pathogens to regulating inflammatory processes in allergies. These roles are represented by distinct cellular phenotypes that we captured with mass cytometry (CyTOF). Our protocol enables simultaneous evaluation of human basophils, eosinophils, and neutrophils under homeostasis and upon immune activation by anti-Immunoglobulin E (anti-IgE) or interleukin-3 (IL-3). Granulocyte integrity and detection of protein markers were optimized so that rare granulocyte populations could be deeply characterized by single cell mass cytometry.For complete details on the use and execution of this protocol, please refer to Vivanco Gonzalez et al. (2020).
Keywords	Cell isolation ; Single Cell ; Flow Cytometry/Mass Cytometry ; Health Sciences ; Immunology ; Antibody ; Science (General) ; Q1-390
Language	English
Publishing date	2022-06-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Giant magnetoresistive sensor array for sensitive and specific multiplexed food allergen detection

Ng, Elaine / Kari C. Nadeau / Shan X. Wang

Biosensors & bioelectronics. 2016 June 15, v. 80

2016

Abstract: Current common allergen detection methods, including enzyme-linked immunosorbent assays (ELISAs) and dip-stick methods, do not provide adequate levels of sensitivity and specificity for at-risk allergic patients. A method for performing highly sensitive ... ...

Abstract	Current common allergen detection methods, including enzyme-linked immunosorbent assays (ELISAs) and dip-stick methods, do not provide adequate levels of sensitivity and specificity for at-risk allergic patients. A method for performing highly sensitive and specific detection of multiple food allergens is thus imperative as food allergies are becoming increasingly recognized as a major healthcare concern, affecting an estimated 4% of the total population. We demonstrate first instance of sensitive and specific multiplexed detection of major peanut allergens Ara h 1 and Ara h 2, and wheat allergen Gliadin using giant magnetoresistive (GMR) sensor arrays. Commercialized ELISA kits for Ara h 1 and Ara h 2 report limits of detection (LODs) at 31.5ng/mL and 0.2ng/mL, respectively. In addition, the 96-well-based ELISA developed in-house for Gliadin was found to have a LOD of 40ng/mL. Our multiplexed GMR-based assay demonstrates the ability to perform all three assays on the same chip specifically and with sensitivities at LODs about an order of magnitude lower than those of 96-well-based ELISAs. LODs of GMR-based assays developed for Ara h 1, Ara h 2, and Gliadin were 7.0ng/mL, 0.2ng/mL, and 1.5ng/mL, respectively, with little to no cross-reactivity. These LODs are clinically important as some patients could react strongly against such low allergen levels. Given the limitations of current industrial detection technology, multiplexed GMR-based assays provide a method for highly sensitive and specific simultaneous detection of any combination of food-product allergens, thus protecting allergic patients from life-threatening events, including anaphylaxis, by unintentional consumption.
Keywords	allergens ; anaphylaxis ; biosensors ; commercialization ; cross reaction ; detection limit ; enzyme-linked immunosorbent assay ; food allergies ; gliadin ; health services ; patients ; peanuts ; wheat
Language	English
Dates of publication	2016-0615
Size	p. 359-365.
Publishing place	Elsevier B.V.
Document type	Article
ZDB-ID	1011023-9
ISSN	1873-4235 ; 0956-5663
ISSN (online)	1873-4235
ISSN	0956-5663
DOI	10.1016/j.bios.2016.02.002
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Synthetic Siglec‑9 Agonists Inhibit Neutrophil Activation Associated with COVID-19

Corleone S. Delaveris / Aaron J. Wilk / Nicholas M. Riley / Jessica C. Stark / Samuel S. Yang / Angela J. Rogers / Thanmayi Ranganath / Kari C. Nadeau / Catherine A. Blish / Carolyn R. Bertozzi

ACS Central Science, Vol 7, Iss 4, Pp 650-

2021 Volume 657

Keywords	Chemistry ; QD1-999
Language	English
Publishing date	2021-03-01T00:00:00Z
Publisher	American Chemical Society
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Air pollution exposure is linked with methylation of immunoregulatory genes, altered immune cell profiles, and increased blood pressure in children

Mary Prunicki / Nicholas Cauwenberghs / Justin Lee / Xiaoying Zhou / Hesam Movassagh / Elizabeth Noth / Fred Lurmann / S. Katharine Hammond / John R. Balmes / Manisha Desai / Joseph C. Wu / Kari C. Nadeau

Scientific Reports, Vol 11, Iss 1, Pp 1-

2021 Volume 12

Abstract: Abstract Ambient air pollution exposure is associated with cardiovascular dysregulation and immune system alterations, yet no study has investigated both simultaneously in children. Understanding the multifaceted impacts may provide early clues for ... ...

Abstract	Abstract Ambient air pollution exposure is associated with cardiovascular dysregulation and immune system alterations, yet no study has investigated both simultaneously in children. Understanding the multifaceted impacts may provide early clues for clinical intervention prior to actual disease presentation. We therefore determined the associations between exposure to multiple air pollutants and both immunological outcomes (methylation and protein expression of immune cell types associated with immune regulation) and cardiovascular outcomes (blood pressure) in a cohort of school-aged children (6–8 years; n = 221) living in a city with known elevated pollution levels. Exposure to fine particular matter (PM2.5), carbon monoxide (CO), and ozone (O3) was linked to altered methylation of most CpG sites for genes Foxp3, IL-4, IL-10 and IFN-g, all involved in immune regulation (e.g. higher PM2.5 exposure 1 month prior to the study visit was independently associated with methylation of the IL-4 CpG24 site (est = 0.16; P = 0.0095). Also, immune T helper cell types (Th1, Th2 and Th17) were associated with short-term exposure to PM2.5, O3 and CO (e.g. Th1 cells associated with PM2.5 at 30 days: est = − 0.34, P < 0.0001). Both B cells (est = − 0.19) and CD4+ cells (est = 0.16) were associated with 1 day NO2 exposure (P ≤ 0.031), whereas CD4+ and CD8+ cells were associated with chronic exposure to PAH456, NOx and/or NO2 (P ≤ 0.038 for all). Finally, diastolic BP (DBP) was inversely associated with long-term exposures to both CO and PAH456, and both systolic and pulse pressure were associated with short-term NO2 and chronic NOx exposure. Our findings demonstrate links between air pollution exposure and methylation of immunoregulatory genes, immune cell profiles and blood pressure, suggesting that even at a young age, the immune and cardiovascular systems are negatively impacted by exposure to air pollution.
Keywords	Medicine ; R ; Science ; Q
Subject code	333
Language	English
Publishing date	2021-02-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Mass Cytometry Phenotyping of Human Granulocytes Reveals Novel Basophil Functional Heterogeneity

Nora Vivanco Gonzalez / John-Paul Oliveria / Dmitry Tebaykin / Geoffrey T. Ivison / Kaori Mukai / Mindy M. Tsai / Luciene Borges / Kari C. Nadeau / Stephen J. Galli / Albert G. Tsai / Sean C. Bendall

iScience, Vol 23, Iss 11, Pp 101724- (2020)

2020

Abstract: Summary: Basophils, the rarest granulocyte, play critical roles in parasite- and allergen-induced inflammation. We applied mass cytometry (CyTOF) to simultaneously asses 44 proteins to phenotype and functionally characterize neutrophils, eosinophils, and ...

Abstract	Summary: Basophils, the rarest granulocyte, play critical roles in parasite- and allergen-induced inflammation. We applied mass cytometry (CyTOF) to simultaneously asses 44 proteins to phenotype and functionally characterize neutrophils, eosinophils, and basophils from 19 healthy donors. There was minimal heterogeneity seen in eosinophils and neutrophils, but data-driven analyses revealed four unique subpopulations within phenotypically basophilic granulocytes (PBG; CD45+HLA-DR−CD123+). Through CyTOF and fluorescence-activated cell sorting (FACS), we classified these four PBG subpopulations as (I) CD16lowFcεRIhighCD244high (88.5 ± 1.2%), (II) CD16highFcεRIhighCD244high (9.1 ± 0.4%), (III) CD16lowFcεRIlowCD244low (2.3 ± 1.3), and (IV) CD16highFcεRIlowCD244low (0.4 ± 0.1%). Prospective isolation confirmed basophilic-morphology of PBG I–III, but neutrophilic-morphology of PBG IV. Functional interrogation via IgE-crosslinking or IL-3 stimulation demonstrated that PBG I–II had significant increases in CD203c expression, whereas PBG III–IV remained unchanged compared with media-alone conditions. Thus, PBG III–IV could serve roles in non-IgE-mediated immunity. Our findings offer new perspectives in human basophil heterogeneity and the varying functional potential of these new subsets in health and disease.
Keywords	Immunology ; Systems Biology ; Science ; Q
Subject code	610
Language	English
Publishing date	2020-11-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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