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High-throughput proteomics using submicroliter amounts of plasma for comprehensive assessment of the immune status

使用亚微升血浆进行高通量蛋白质组学综合评估免疫状态

基本信息

批准号：
10381719
负责人：
Hanno Steen
金额：
$ 117.82万
依托单位：
BOSTON CHILDREN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-04-09 至 2025-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10381719
关键词：
Adolescent Adult Agreement Aliquot Antibodies Antibody titer measurement Autoimmunity Bacterial Infections Biological Assay Biological Markers Blood Plasma Volume Blood Volume Boston C-reactive protein Cells Communicable Diseases Communities Complement Consumption Data Development Disease Elderly Erythrocyte Sedimentation Rate Fibrinogen Frail Elderly Funding Funding Opportunities Future Health Hepatitis B Surface Antigens Hepatitis B Vaccination Hepatitis B Vaccines Human Human body Hypersensitivity Immune Immune response Immune system Immunity Immunoglobulin Domain Immunoglobulins Immunologic Deficiency Syndromes Immunologic Monitoring Immunology Individual Infection Maps Measures Methods Modality Molecular Monitor Mycoses National Institute of Allergy and Infectious Disease Neonatal Newborn Infant Organism Parasitic infection Participant Patients Pediatric Hospitals Persons Plasma Plasma Proteins Population Populations at Risk Preparation Prevention Proteins Proteome Proteomics Regulation Research Research Design Resolution Sampling Serology Set protein Specimen System Systems Biology Term Birth Testing Time Transplantation Vaccine Design Virus Diseases Vulnerable Populations Work age group anti-hepatitis B base clinical biomarkers cohort complement pathway complement system experimental study gene product immune function immunological status immunoregulation improved innovation insight interest liquid chromatography mass spectrometry milliliter nanolitre novel premature preterm newborn procalcitonin response vaccine immunogenicity vaccinology

项目摘要

SUMMARY Often, many different tests are performed to obtain a multiparameter assessment of the innate and adaptive immune status. Such tests often include erythrocyte sedimentation rate, C-reactive protein (CRP), procalcitonin, various complement pathway proteins, total antibody (Ab) isotypes and/or subclasses, and specific Ab titers. All these tests are performed on different analytical platforms requiring a separate aliquot for each test. Thus, even with modest sample consumption per test, there is a substantial cumulative volume required for multiple independent tests. While these sample requirements may not be prohibitive for healthy adolescents and adults, they are particularly challenging in especially vulnerable populations such as premature newborns, and frail and/or elderly individuals. For these populations, a wide range of different tests is often very important, however, samples are often limited. In agreement with the purpose of the funding opportunity “Development of Sample Sparing Assays for Monitoring Immune Responses”, we propose to move four different protein assays onto a common processing and analysis platform, which can be performed on the same submicroliter aliquot of plasma thereby significantly reducing the sample volume requirements. The four protein assays of interest include i) an expanded panel of complement components, ii) CRP, iii) antibody isotypes and subclasses including a novel and innovative immunoglobulin domain-resolved map of the IgOme-related protein repertoire (aka IgOme), and iv) the classical plasma proteome, i.e. ~400 well described proteins many of which of clear immunological function. The quantitative information from all these assays will provide us with an exquisite map of the immune status, a hypothesis that we will be tested by correlating our findings with the anti-hepatitis B titer measured before and after hepatitis B vaccination in >500 newborns. Samples will be provided by Boston Children's Hospital's NIAID-funded HIPC (Human Immunology Project Consortium), which will significantly increase the impact of this cohort beyond its original scope. Taking the request of this funding opportunity for sample sparing to a different level, we will advance our plasma proteomics pipeline to quadruple the throughput to at least 96 samples/day and to quarter the plasma volume requirements to <100 nanoliter. Thus, in the future, 1 microliter of plasma will be sufficient for tens of temporally independent LC/MS- based protein assays, resulting in quantitative information for hundreds of proteins such that even a miniscule amount of plasma from the smallest and/or most frail patients will be sufficient to establish an exquisitely detailed and unbiased molecular map of immune status of any person.

总结