Development of Mucosal and Systemic Immunity and Risk of Food Allergy

粘膜和系统免疫的发展以及食物过敏的风险

• 批准号: 10265645
• 负责人: Kirsi Jarvinen-Seppo
• 金额: $ 24.52万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-04-01 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10265645
• 关键词: 16S ribosomal RNA sequencing; Age-Months; Allergens; Allergic; Allergic Disease; Allergy to peanuts; Animal Model; Animals; Antibiotics; Antibodies; Antibody Response; Autoimmune Diseases; B-Cell Development; B-Lymphocyte Subsets; B-Lymphocytes; Bacteria; Biological Markers; Birth; Cattle; Child; Childhood; Childhood Asthma; Clinical; Clinical Trials; Cohort Studies; Consumption; Data; Defect; Developed Countries; Development; Disease; Eczema; Environmental Risk Factor; Exhibits; Exposure to; Extrinsic asthma; Family; Farming environment; Feces; Flow Cytometry; Food; Food Hypersensitivity; Future; Genomics; Germ-Free; Home; Hypersensitivity; IgE; Immune; Immune response; Immune system; Immunity; Immunoglobulin A; Immunoglobulin Class Switching; Immunoglobulin G; Immunoglobulin Variable Region; Immunoglobulins; Immunology; Infant; Infant Development; Intervention; Knowledge; Learning; Life; Life Style; Measures; Memory B-Lymphocyte; Mennonite; Milk; Mucosal Immunity; Mucous Membrane; Neonatal; Oral; Outcome; Plasma Cells; Play; Population; Predisposition; Prevention; Research; Risk; Role; Saliva; Secretory Immunoglobulin A; Serum; Somatic Mutation; Sorting - Cell Movement; Systems Development; T-Lymphocyte; Training; Transcript; Umbilical Cord Blood; Vaginal delivery procedure; animal data; atopy; base; cohort; design; dietary; early onset; food allergen; gut microbiome; gut microbiota; high risk; high risk population; immunogenic; immunogenicity; infancy; microbial; microbiome; microorganism antigen; mucosal site; neonate; peripheral blood; postnatal; prevent; response; support vector machine; urban setting

Background: Transmission of the SARS-CoV-2 virus in human milk (HM) is unknown with only 11 poorly-described studies, reporting detectable virus in just 1 of the total 36 breastmilk samples. Further, it is possible that maternal SARS-CoV-2 infection during pregnancy and lactation confers some specific protection through antibodies. Only one study reports the presence of IgG to SARS-CoV-2 in HM. Alarming examples of antibody-dependent enhancement of other viral infections illustrate how critical it is to understand both the profile and activity of these antibodies in HM. It is critical then to understand the transmission risks and protective factors between mother and child through breastfeeding. Design: We propose a longitudinal cohort study of COVID-19+ mothers to determine risks of transmission (viral exposure of infants through breastfeeding by presence in HM and on areolar skin) and protective factors (SARS-CoV-2-specific antibody response in HM, profile and neutralization capacity) of breastfeeding. Longitudinal samples will allow us to assess temporal changes over disease course. Methods: We will enroll 50 COVID+ mothers in the first 3 months of lactation, 25 symptomatic and 25 asymptomatic. We will concurrently collect samples from two locations: The University of Rochester School of Medicine and Dentistry and New York University, NY. These sites will provide robust and staggered access to patients. We will recruit through local hospitals and social media platforms. Mothers will provide informed eConsent. IRB approval has been received. All samples will be self-collected in the hospital (if admitted) or in the home. There will be no physical contact between study staff and participants. Mothers will express and collect whole breastmilk on Days 0 (enrollment), 3, 10, 19, 28, and 90, breast skin swabs on Days 0 and 3 and whole blood by fingerstick on days 0 and 90. They will also be instructed to provide a frozen HM sample from Day -7, if available. Analysis: RNA will be extracted from HM and breast skin swabs in the Jarvinen-Seppo lab. SARS- CoV-2 genomic RNA will be quantitated using RT-qPCR three amplicon probe-based system as recommended by CDC. We will compare presence and changes in SARS-CoV-2 in HM via repeated measures analysis. We will assess SARS-CoV-2 and other coronavirus antibodies in maternal finger prick and HM to S and N proteins of SARS1, SARS2, HKU1, 229E, NL63 and OC43 by Luminex on the mPLEX-CoV system developed and validated by the Zand lab. Repeated measures analysis will be used to compare the changes in concentration of HM anti-SARS-CoV-2 antibodies over the time-course of disease progression and also between women with mild to severe symptoms. Impact: These results are critical to understand the risks and benefits of breastfeeding in the context of COVID-19 infection, and are necessary to make evidence-based policies, and to care for these families.

背景：SARS-CoV-2 病毒在人乳 (HM) 中的传播尚不清楚，仅 11 研究描述不充分，报告称在 36 个母乳样本中仅 1 个检测到了病毒。更远， 母亲在怀孕和哺乳期间感染 SARS-CoV-2 可能会导致一些特定的症状 通过抗体进行保护。只有一项研究报告了 SARS-CoV-2 IgG 的存在 在HM。其他病毒感染的抗体依赖性增强的令人震惊的例子说明了如何 至关重要的是了解 HM 中这些抗体的概况和活性。那么至关重要的是 了解母婴之间的传播风险和保护因素 哺乳。 设计：我们建议对 COVID-19+ 母亲进行纵向队列研究，以确定感染的风险 传播（婴儿通过母乳喂养接触病毒，存在于HM和乳晕皮肤上） 和保护因素（HM 中的 SARS-CoV-2 特异性抗体反应、概况和中和 的能力）的母乳喂养。纵向样本将使我们能够评估疾病的时间变化 课程。 方法：我们将招募 50 名处于哺乳期前 3 个月的新冠肺炎母亲，其中 25 名有症状，25 名有症状。 无症状。我们将同时从两个地点收集样本： 罗切斯特大学 医学和牙科学院和纽约大学，纽约。这些网站将提供强大且 错开接触患者。我们将通过当地医院和社交媒体平台进行招募。母亲们 将提供知情的电子同意。已收到 IRB 批准。所有样品将在以下地点自行收集 医院（如果入院）或家中。研究人员之间不会有身体接触 和参与者。母亲将在第 0 天（注册）、第 3 天、第 10 天、第 19 天、 28 和 90，在第 0 天和第 3 天采集乳房皮肤拭子，在第 0 天和第 90 天采集指尖采血。 还将被指示从第-7天起提供冷冻 HM 样本（如果有）。 分析：RNA 将从 Jarvinen-Seppo 实验室的 HM 和乳房皮肤拭子中提取。非典- 将使用基于三扩增子探针的 RT-qPCR 系统对 CoV-2 基因组 RNA 进行定量 按照疾病预防控制中心的建议。我们将通过重复比较 HM 中 SARS-CoV-2 的存在和变化 措施分析。我们将评估母体手指中的 SARS-CoV-2 和其他冠状病毒抗体 prick 和 HM 对 SARS1、SARS2、HKU1、229E、NL63 和 OC43 的 S 和 N 蛋白（由 Luminex 提供） mPLEX-CoV 系统由 Zand 实验室开发和验证。重复测量分析 用于比较 HM 抗 SARS-CoV-2 抗体浓度随时间的变化 疾病进展以及具有轻度至重度症状的女性之间。 影响：这些结果对于了解母乳喂养的风险和益处至关重要 COVID-19 感染，对于制定基于证据的政策并照顾这些家庭是必要的。

项目成果

Food allergy, breastfeeding, and introduction of complementary foods in the New York Old Order Mennonite Community.

纽约旧秩序门诺派社区的食物过敏、母乳喂养和补充食品的引入。

• 发表时间: 2020
• 作者: Phillips, Jonathan T;Stahlhut, Richard W;Looney, Richard J;Järvinen, Kirsi M
• 通讯作者: Järvinen, Kirsi M

Association of Human Milk Antibody Induction, Persistence, and Neutralizing Capacity With SARS-CoV-2 Infection vs mRNA Vaccination.

母乳抗体诱导、持久性和中和能力与 SARS-CoV-2 感染与 mRNA 疫苗接种的关系。

• 发表时间: 2022-02-01
• 影响因子: 26.1
• 作者: Young, Bridget E;Seppo, Antti E;Diaz, Nichole;Rosen;Nowak;Cruz Vasquez, Joseline M;Ferri;Nguyen;Fitzgerald, Theresa;Sangster, Mark Y;Topham, David J;Järvinen, Kirsi M
• 通讯作者: Järvinen, Kirsi M

Biomarkers of Development of Immunity and Allergic Diseases in Farming and Non-farming Lifestyle Infants: Design, Methods and 1 Year Outcomes in the "Zooming in to Old Order Mennonites" Birth Cohort Study.

农业和非农业生活方式婴儿免疫和过敏性疾病发展的生物标志物：“放大旧秩序门诺派”出生队列研究的设计、方法和一年结果。

• 发表时间: 2022
• 作者: Järvinen, Kirsi M;Davis, Erin C;Bevec, Erin;Jackson, Courtney M;Pizzarello, Catherine;Catlin, Elizabeth;Klein, Miranda;Sunkara, Akhila;Diaz, Nichole;Miller, James;Martina, Camille A;Thakar, Juilee;Seppo, Antti E;Looney, R John;Collaborative
• 通讯作者: Collaborative

Environmental Exposures may Hold the Key; Impact of Air Pollution, Greenness, and Rural/Farm Lifestyle on Allergic Outcomes.

环境暴露可能是关键；

• 发表时间: 2023-02
• 影响因子: 5.5
• 作者: Jackson, Courtney M;Kaplan, Alexandra N;Järvinen, Kirsi M
• 通讯作者: Järvinen, Kirsi M

Ecologies, synergies, and biological systems shaping human milk composition-a report from "Breastmilk Ecology: Genesis of Infant Nutrition (BEGIN)" Working Group 2.

塑造母乳成分的生态、协同作用和生物系统——“母乳生态学：婴儿营养的起源（开始）”第二工作组的报告。

• 发表时间: 2023-04
• 作者: Smilowitz, Jennifer T;Allen, Lindsay H;Dallas, David C;McManaman, James;Raiten, Daniel J;Rozga, Mary;Sela, David A;Seppo, Antti;Williams, Janet E;Young, Bridget E;McGuire, Michelle K
• 通讯作者: McGuire, Michelle K