Infection, fever and immune signatures in an autism birth cohort

自闭症出生队列中的感染、发烧和免疫特征

• 批准号: 8928709
• 负责人: MADY HORNIG
• 金额: $ 78.85万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-30 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8928709
• 关键词: Abbreviations; Acetaminophen; Address; Adrenal Glands; Affect; Allergic; Analgesic and Antipyretic; Analgesics; Animal Model; Antibiotics; Antibodies; Attenuated; Autistic Disorder; Autoimmune Process; Biological; Biological Assay; Biological Markers; Birth; Blood specimen; Brain; Child; Chronic Fatigue Syndrome; Clinical; Clinical Data; Clinical assessments; Collection; Complement; Confidence Intervals; Cytomegalovirus; Data; Development; Diet; Disease; Early Diagnosis; Early Intervention; Economic Burden; Environmental Exposure; Epidemiology; Escherichia coli; Event; Exposure to; Fathers; Fever; Folate; Funding; Genetic Predisposition to Disease; Health; Herpesvirus 1; Hypothalamic structure; Immune; Immune System Diseases; Immune response; Immunity; Immunoassay; Immunoprecipitation; Individual; Infant; Infection; Infectious Agent; Inflammation; Inflammatory; Inflammatory Response; Institutes; Intake; Interferons; Life; Luciferases; Measures; Mediating; Medical; Microbe; Micronutrients; Modeling; Molecular; Mothers; Neuraxis; Neurodevelopmental Disability; Non-Steroidal Anti-Inflammatory Agents; Norway; Odds Ratio; Outcome; Pathogenesis; Patients; Pattern; Pharmaceutical Preparations; Pituitary Gland; Plasma; Pregnancy; Public Health; Questionnaires; Registries; Relative (related person); Research; Resources; Risk; Role; Rubella virus; Sample Size; Sampling; Schizophrenia; Serologic tests; Serological; Simplexvirus; Streptococcus Group B; System; Testing; Time; Toxoplasma gondii; Toxoplasmosis; Tryptophan; Umbilical Cord Blood; United States National Institutes of Health; Vitamin D; Zinc; antipyretic; autism spectrum disorder; cohort; data registry; design; developmental disease; disorder control; disorder risk; fighting; high throughput screening; immune activation; immune function; influenzavirus; insight; novel; pathogen; population based; postnatal; pregnant; prenatal; prospective; psychosocial

DESCRIPTION (provided by applicant): Evidence from epidemiologic and animal model studies of autism (ASD) supports a role for pre- and postnatal immune and infectious factors in autism pathogenesis. However, associations with specific pathogens, patterns of immune response, fever and exposure to antibiotics, antipyretics, analgesics and micronutrients have not been rigorously addressed. This project will leverage the unique resources of the Norwegian Autism Birth Cohort (ABC) and the Center for Infection and Immunity (CII) for insights into the role of infection, immunity and inflammation in autism through pursuit of three complementary aims that address not only immune activation, fever and drug and micronutrient exposures during gestation per se, but also the timing of these phenomena. In Aim 1 we will investigate the relationship of infectious, immune and inflammatory events to ASD risk using prospective questionnaire data about the following exposures in ASD and control mother- child pairs: a) infection; b) presence, timing and duration of fever, c) autoimmune and allergic conditions, d) antipyretics (acetaminophen, nonsteroidal anti-inflammatory drugs [NSAIDs]), analgesics and antibiotics, and e) micronutrients that modify immune function (vitamin D, zinc) or mitigate antibiotic anti-folate effects (folate). In Aim 2 we will define the immune signatures associated with ASD using multiplexed immunoassays (Luminex) to compare levels of 61 immune/inflammatory molecules in plasma samples from ASD and control mothers (mid-gestation, birth) and children (umbilical cord blood). In Aim 3 we will examine the role of specifi infectious agents in ASD by measuring maternal and child antibodies to influenza virus; ToRCH pathogens T. gondii, rubellavirus, cytomegalovirus and herpes simplex viruses 1 and 2; and Group B streptococcus and E. coli using luciferase immunoprecipitation systems (LIPS) and multiplexed immunoassays (Luminex). In concert these aims have the potential to identify factors and biomarkers for ASD risk that could facilitate early diagnosis and intervention. The Research Council of Norway has reviewed the proposal and guaranteed funding to a maximum of NOK 5 million ($834,000), to support the Norwegian segment of the project, contingent on NIH support.

描述（由申请人提供）：来自自闭症（ASD）流行病学和动物模型研究的证据支持产前和产后免疫和感染因素在自闭症发病机制中的作用。然而，与特定病原体、免疫反应模式、发烧以及接触抗生素、退热药、镇痛药和微量营养素的关系尚未得到严格解决。该项目将利用挪威自闭症出生队列 (ABC) 和感染与免疫中心 (CII) 的独特资源，通过追求三个互补的目标，不仅解决免疫问题，还深入了解感染、免疫和炎症在自闭症中的作用。妊娠期间的激活、发烧、药物和微量营养素暴露，以及这些现象发生的时间。在目标 1 中，我们将使用有关 ASD 和对照母子对以下暴露的前瞻性问卷数据来调查感染、免疫和炎症事件与 ASD 风险的关系：a) 感染； b) 发烧的存在、时间和持续时间，c) 自身免疫性和过敏性疾病，d) 退烧药（对乙酰氨基酚、非甾体抗炎药 [NSAID]）、镇痛药和抗生素，以及 e) 改变免疫功能的微量营养素（维生素 D、锌） ）或减轻抗生素抗叶酸作用（叶酸）。在目标 2 中，我们将使用多重免疫测定 (Luminex) 来定义与 ASD 相关的免疫特征，以比较 ASD 和对照母亲（妊娠中期、出生）和儿童（脐带血）血浆样本中 61 种免疫/炎症分子的水平。在目标 3 中，我们将通过测量母婴流感病毒抗体来研究特定传染源在 ASD 中的作用； ToRCH病原体弓形虫、风疹病毒、巨细胞病毒和单纯疱疹病毒1型和2型；使用荧光素酶免疫沉淀系统 (LIPS) 和多重免疫测定 (Luminex) 检测 B 组链球菌和大肠杆菌。综上所述，这些目标有可能确定 ASD 风险的因素和生物标志物，从而促进早期诊断和干预。挪威研究委员会已审查该提案，并保证提供最多 500 万挪威克朗（834,000 美元）的资金，以支持该项目的挪威部分，具体取决于 NIH 的支持。