Basic and Translational Mechanisms of Alloimmunization to RBC Transfusion Scientific Core A
红细胞输血同种免疫的基本和转化机制 科学核心 A
基本信息
- 批准号:10711667
- 负责人:
- 金额:$ 66.42万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-09-10 至 2028-06-30
- 项目状态:未结题
- 来源:
- 关键词:AcuteAdultAfricanAliquotAlloantigenAlloimmunizationBiologyBloodBlood TransfusionBlood specimenBrazilCaringCell CommunicationChronicClinicalCollaborationsCollectionComplicationConsentDNADataDatabasesElectronic MailEnsureEnvironmentErythrocyte TransfusionErythrocytesEventFreezingGene ExpressionGenetic TranscriptionHealthcareHemoglobinopathiesHospitalsImmunizeIndividualInflammationInvestigationIsoantibodiesLabelLaboratoriesLeukocytesLinkMetadataOdds RatioParticipantPathway interactionsPatientsPediatric HospitalsPeripheral Blood Mononuclear CellPhenotypePhysiciansPopulationPositioning AttributeReportingResearchResearch PersonnelRiskRoleSamplingSampling StudiesSickle Cell AnemiaSiteSourceTelephoneTest ResultTestingTherapeutic InterventionTimeTrans-Omics for Precision MedicineTransfusionValidationVariantVenous blood samplingbiobankclinical applicationclinical materialclinical phenotypecohortexperienceexperimental studygenetic variantgenome analysisgenome sequencinghospital carehuman studyhuman subjectimmunogenicityinsightinterestmeetingsparticipant enrollmentpediatric patientsperipheral bloodprogramsprospectiveresponders and non-responderssingle-cell RNA sequencingtherapeutic developmenttranscriptometransfusion medicinewhole genome
项目摘要
Project Summary/Abstract:
Individuals with sickle cell disease (SCD) have a significantly higher red blood cell (RBC) alloimmunization rate
than other populations receiving transfused donor RBCs. Depending on the study, circumstances of transfusion,
and environment, it has been reported that 18-47% of individuals with SCD become immunized to RBC allo-
antigens following a transfusion and are also more likely to then make additional alloantibodies with subsequent
transfusions. Transfusions in the setting of an acute SCD complication have an 8-12-fold higher odds ratio(1) of
resulting in alloantibody formation compared to those given at steady-state. We hypothesize that we will identify
key drivers of alloimmunization with a large-scale, unbiased human study that integrates recipient omics and
environmental conditions (i.e., presence or absence of acute illness and high levels of inflammation) at the time
of transfusion. We will test this through first identifying variants associated with alloimmunization through analysis
of genome sequencing (WGS) from responders and non-responders. We hypothesize that SCD individuals with
African heritage will have genetic variants associated with increased immunogenicity. To test this, we will
analyze the WGS of our Emory SCD cohort (n=2000) who have or have not developed alloantibodies after 10
or more blood transfusions and compare to WGS from the REDSIII cohort in TOPMed, which has
alloimmunization phenotypes on 2800 subjects with SCD from Brazil. Then, we will assess transcriptome
changes of leukocyte subsets at baseline, at time of transfusion, and at one-month post-transfusion in individuals
with SCD who did or did not develop alloimmunization. We hypothesize that we will identify alterations in gene
expression (and affiliated pathways) that associate with alloimmunization. This will have the immediate benefit
of allowing us to develop a transcriptional risk score (TRS) for alloimmunization, and the longer-term benefit if
identifying pathways for rational development of therapeutic interventions. Finally, we will assess the impact of
inflammation on alloimmunization. We hypothesize that alloimmunization in individuals with SCD that occur in
the setting of acute inflammation differs mechanistically from that of alloimmunization that occurs in the setting
of chronic transfusion or in healthy individuals. We will compare the transcriptomes obtained in aim 2 to
scRNAseq data obtained from stored PBMCs from a cohort of 40 non-SCD individuals who developed
alloantibodies when challenged by Rh mismatched RBCs. We predict our analysis will allow us to identify
individuals at risk for alloimmunization before it occurs, and elucidate the role of inflammation in
alloimmunization, both in patients with SCD and in healthy individuals.
项目总结/文摘:
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Vivien Andrea Sheehan其他文献
Vivien Andrea Sheehan的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Vivien Andrea Sheehan', 18)}}的其他基金
Basic and Translational Mechanisms of Alloimmunization to RBC Transfusion. Project 4
红细胞输注同种免疫的基本和转化机制。
- 批准号:
10711671 - 财政年份:2023
- 资助金额:
$ 66.42万 - 项目类别:
A Genomics Approach to Gamma-Globin Regulation
伽马珠蛋白调控的基因组学方法
- 批准号:
9164151 - 财政年份:2016
- 资助金额:
$ 66.42万 - 项目类别:
相似海外基金
A neuroimaging approach to advance mechanistic understanding of tobacco use escalation risk among young adult African American vapers
一种神经影像学方法,可促进对年轻非洲裔美国电子烟使用者烟草使用升级风险的机制理解
- 批准号:
10509308 - 财政年份:2022
- 资助金额:
$ 66.42万 - 项目类别:
Understanding social undermining of weight management behaviors in young adult African American women
了解年轻非洲裔美国女性体重管理行为的社会破坏
- 批准号:
10680412 - 财政年份:2022
- 资助金额:
$ 66.42万 - 项目类别:
Understanding social undermining of weight management behaviors in young adult African American women
了解年轻非洲裔美国女性体重管理行为的社会破坏
- 批准号:
10535890 - 财政年份:2022
- 资助金额:
$ 66.42万 - 项目类别:
A neuroimaging approach to advance mechanistic understanding of tobacco use escalation risk among young adult African American vapers
一种神经影像学方法,可促进对年轻非洲裔美国电子烟使用者烟草使用升级风险的机制理解
- 批准号:
10629374 - 财政年份:2022
- 资助金额:
$ 66.42万 - 项目类别:
Impact of Adult Day Services on Psychosocial and Physiological Measures of Stress among African American Dementia Family Caregivers
成人日间服务对非裔美国痴呆症家庭护理人员的社会心理和生理压力测量的影响
- 批准号:
10553725 - 财政年份:2021
- 资助金额:
$ 66.42万 - 项目类别:
Voice-Activated Technology to Improve Mobility & Reduce Health Disparities: EngAGEing African American Older Adult-Care Partner Dyads
语音激活技术可提高移动性
- 批准号:
10494191 - 财政年份:2021
- 资助金额:
$ 66.42万 - 项目类别:
Impact of Adult Day Services on Psychosocial and Physiological Measures of Stress among African American Dementia Family Caregivers
成人日间服务对非裔美国痴呆症家庭护理人员的社会心理和生理压力测量的影响
- 批准号:
10328955 - 财政年份:2021
- 资助金额:
$ 66.42万 - 项目类别:
Voice-Activated Technology to Improve Mobility & Reduce Health Disparities: EngAGEing African American Older Adult-Care Partner Dyads
语音激活技术可提高移动性
- 批准号:
10437374 - 财政年份:2021
- 资助金额:
$ 66.42万 - 项目类别:
Voice-Activated Technology to Improve Mobility & Reduce Health Disparities: EngAGEing African American Older Adult-Care Partner Dyads
语音激活技术可提高移动性
- 批准号:
10654831 - 财政年份:2021
- 资助金额:
$ 66.42万 - 项目类别:
Development, Implementation, and Evaluation of a Smoking Cessation Intervention Tailored to Rural Young Adult African American Men: Toward Scalability
针对农村年轻非裔美国男性的戒烟干预措施的制定、实施和评估:走向可扩展性
- 批准号:
9896786 - 财政年份:2018
- 资助金额:
$ 66.42万 - 项目类别:














{{item.name}}会员




