5 results on '"Upton, Julia E. M."'
Search Results
2. Precision cut intestinal slices, a novel model of acute food allergic reactions
- Author
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Hung, Lisa, Celik, Alper, Yin, Xiaojun, Yu, Kai, Berenjy, Alireza, Kothari, Akash, Obernolte, Helena, Upton, Julia E. M., Lindholm Bøgh, Katrine, Somers, Gino R., Siddiqui, Iram, Grealish, Martin, Quereshy, Fayez A., Sewald, Katherina, Chiu, Priscilla P. L., Eiwegger, Thomas, Hung, Lisa, Celik, Alper, Yin, Xiaojun, Yu, Kai, Berenjy, Alireza, Kothari, Akash, Obernolte, Helena, Upton, Julia E. M., Lindholm Bøgh, Katrine, Somers, Gino R., Siddiqui, Iram, Grealish, Martin, Quereshy, Fayez A., Sewald, Katherina, Chiu, Priscilla P. L., and Eiwegger, Thomas
- Abstract
Background: Food allergy affects up to 10% of the pediatric population. Despite ongoing efforts, treatment options remain limited. Novel models of food allergy are needed to study response patterns downstream of IgE-crosslinking and evaluate drugs modifying acute events. Here, we report a novel human ex vivo model that displays acute, allergen-specific, IgE-mediated smooth muscle contractions using precision cut intestinal slices (PCIS). Methods: PCIS were generated using gut tissue samples from children who underwent clinically indicated surgery. Viability and metabolic activity were assessed from 0-24h. Distribution of relevant cell subsets was confirmed using single nucleus RNA sequencing. PCIS were passively sensitized using plasma from peanut allergic donors or peanut-sensitized non-allergic donors, and exposed to various stimuli including serotonin, histamine, FcɛRI-crosslinker and food allergens. Smooth muscle contractions and mediator release functioned as readouts. A novel program designed to measure contractions was developed to quantify responses. The ability to demonstrate the impact of antihistamines and immunomodulation from peanut oral immunotherapy (OIT) was assessed. Results: PCIS viability was maintained for 24h. Cellular distribution confirmed the presence of key cell subsets including mast cells. The video analysis tool reliably quantified responses to different stimulatory conditions. Smooth muscle contractions were allergen-specific and reflected the clinical phenotype of the plasma donor. Tryptase measurement confirmed IgE-dependent mast cell-derived mediator release. Antihistamines suppressed histamine-induced contraction and plasma from successful peanut OIT suppressed peanut-specific PCIS contraction. Conclusion: PCIS represent a novel human tissue-based model to study acute, IgE-mediated food allergy and pharmaceutical impacts on allergic responses in the gut.
- Published
- 2023
3. Safety and immunogenicity of the live-attenuated varicella vaccine in pediatric solid organ transplant recipients: A systematic review and meta-analysis.
- Author
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Piché-Renaud PP, Yue Lee E, Ji C, Qing Huang JY, Uleryk E, Teoh CW, Morris SK, Top KA, Upton JEM, Vyas MV, and Allen UD
- Subjects
- Adult, Child, Humans, Transplant Recipients, Chickenpox Vaccine adverse effects, Vaccines, Attenuated, Chickenpox prevention & control, Viral Vaccines, Organ Transplantation
- Abstract
This study aimed to synthesize the available evidence on the immunogenicity, safety, and effectiveness of live-attenuated varicella vaccine in solid organ transplant recipients. Medline and EMBASE were searched using predefined search terms to identify relevant studies. The included articles reported varicella vaccine administration in the posttransplant period in children and adults. A pooled proportion of transplant recipients who seroconverted and who developed vaccine-strain varicella and varicella disease was generated. Eighteen articles (14 observational studies and 4 case reports) were included, reporting on 711 transplant recipients who received the varicella vaccine. The pooled proportion was 88.2% (95% confidence interval 78.0%-96.0%, 13 studies) for vaccinees who seroconverted, 0% (0%-1.2%, 13 studies) for vaccine-strain varicella, and 0.8% (0%-4.9%, 9 studies) for varicella disease. Most studies followed clinical guidelines for administering live-attenuated vaccines, with criteria that could include being at least 1 year posttransplant, 2 months postrejection episode, and on low-dose immunosuppressive medications. Varicella vaccination in transplant recipients was overall safe in the included studies, with few cases of vaccine-strain-induced varicella or vaccine failure, and although it was immunogenic, the proportion of recipients who seroconverted was lower than that seen in the general population. Our data support varicella vaccination in select pediatric solid organ transplant recipients., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: This study was supported by funding from The Hospital for Sick Children Transplant and Regenerative Medicine Centre (TRMC). PPPR has been co-investigator on an investigator-led project funded by Pfizer that is unrelated to this study. JU reports being a past investigator for Sanofi/Regeneron, fees from Pfizer and AstraZeneca, all unrelated to vaccines. SKM has received honoraria for lectures from GlaxoSmithKline, was a member of ad hoc advisory boards for Pfizer, Sanofi Pasteur, and Merck and is a co-investigator on an investigator-led grant from Pfizer, all unrelated to this study. All authors have no conflict of interest relevant to this publication to declare. The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation., (Copyright © 2023 American Society of Transplantation & American Society of Transplant Surgeons. Published by Elsevier Inc. All rights reserved.)
- Published
- 2023
- Full Text
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4. Efficacy, effectiveness and other patient-centered outcomes of oral immunotherapy.
- Author
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Upton JEM
- Abstract
Oral immunotherapy (OIT) is the medically supervised ingestion of a food allergen. Understanding of the expected outcomes of OIT allow for risk-benefit assessments for patient-centered decisions. The efficacy of OIT to achieve desensitization in children has been confirmed in multiple meta-analyses, even with vastly disparate study populations and methodologies. Most children initiated on OIT will achieve the ability to eat more allergen before experiencing an allergic reaction than if they continue to avoid their allergen. This effect is diminished without regular ingestion. Previous meta-analyses showed increased allergic reactions on OIT versus avoidance or placebo due to the dosing itself; however, a recent meta-analysis showed that peanut OIT in children did not lead to an increase in allergic reactions. Analysis of emerging data suggests that OIT may reduce reactions to accidental exposures over time. Important patient-centered outcomes, including reaction avoidance or amelioration, and psychosocial impacts and/or quality of life, and studies of more demographically representative populations are also necessary., (Copyright © 2022, The Author(s). Published by OceanSide Publications, Inc., U.S.A.)
- Published
- 2022
- Full Text
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5. Moderate-to-severe lower respiratory tract infection in early life is associated with increased risk of polysensitization and atopic dermatitis: Findings from the CHILD Study.
- Author
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Medeleanu M, Upton JEM, Reyna Vargas ME, Dai R, Mandhane PJ, Simons E, Turvey SE, Subbarao P, and Moraes TJ
- Abstract
Background: Respiratory infections in infancy are associated with the development of allergic asthma and atopy. Delineating whether symptomatic infections are a marker of atopic predisposition or contribute to atopic development is important for preventive strategies. We hypothesized that early, severe lower respiratory tract infections (LRTIs) may be a risk factor for the development of atopic disease., Objective: Our aim was to determine whether clinically defined, moderate-to-severe LRTIs in infancy are associated with the development of atopic dermatitis and allergic sensitization at preschool age., Methods: LRTI timing and severity in the first 18 months of life was defined by using the Canadian Healthy Infant Longitudinal Development study questionnaires. Polysensitization and atopic dermatitis were determined by standardized skin prick testing and structured clinical assessments. Longitudinal associations between LRTI severity and clinical outcomes at ages 3 years and 5 years were determined by adjusted repeated measures generalized estimation equations., Results: Moderate-to-severe LRTIs were associated with increased odds of polysensitization (odds ratio = 1.91 [95% CI = 1.16-3.15]; P = .014) and atopic dermatitis (odds ratio = 2.19 [95% CI 1.41-3.39]; P < .001) as compared with the odds in children with no history of LRTI in the first 18 months of life. The association between moderate-to-severe LRTI and polysensitization or atopic dermatitis remained robust after adjusting for sex; study site; breast-feeding duration; and mother, father, or both-parent atopy or asthma., Conclusions: These results highlight severe infant LRTI as an important risk factor for allergic and atopic disease (ie, polysensitization and atopic dermatitis), and they suggest that this risk is independent of maternal in utero environment, both-parent history of asthma, and both-parent genetic predisposition., (Crown Copyright © 2022 Published by Elsevier Inc. on behalf of the American Academy of Allergy, Asthma & Immunology.)
- Published
- 2022
- Full Text
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