Protecting Fetuses and Newborns from Maternal RBC Alloantibodies

保护胎儿和新生儿免受母体红细胞同种抗体的影响

基本信息

  • 批准号:
    9069975
  • 负责人:
  • 金额:
    $ 42.28万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2014
  • 资助国家:
    美国
  • 起止时间:
    2014-07-15 至 2019-06-30
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Maternal RBC alloimmunization, induced by prior pregnancy/delivery or prior transfusion, puts the developing fetus/neonate at risk for anemia and hemolytic disease of the fetus and newborn (HDFN). 1 in 600 infants is at risk for HDFN, with no targeted therapies available to offer alloimmunized pregnant women, and no prophylactic therapies available for non-D antigens. This paucity of targeted therapies is due in part to an understandable reluctance to test innovative therapies on pregnant women or their fetuses. To circumvent this issue, we have developed what we believe is the first animal model of HDFN in which pregnancy/delivery is capable of stimulating maternal alloimmunization and in which these maternal antibodies result in HDFN. The fact that this model involves RBC specific expression of a human antigen highly implicated in HDFN (KEL) adds further to its innovation. As an extension of our R21 to develop and characterize this model, we now propose to utilize this model to protect developing fetuses from existing maternal alloantibodies in a damage control manner, and to prevent primary anti-KEL formation in a prophylactic manner. Central Hypothesis: The dangers of existing or developing maternal anti-RBC alloantibodies to fetuses and newborns can be prevented through active or passive maternal immunomodulatory therapies. Specific Aim 1: Investigate strategies to minimize the dangers of existing maternal anti-KEL alloantibodies to developing fetuses and newborns. Specific Aim 2: Investigate strategies to prevent primary anti-KEL RBC alloimmunization during pregnancy/delivery. Specific Aim 3: Investigate the impact of other (non-KEL) RBC alloantibodies on developing fetuses and newborn. Public Health Significance/Long Term Goals: The development of targeted therapies to minimize the dangers of existing RBC alloantibodies or to prevent primary alloimmunization in women carrying fetuses expressing the cognate RBC antigen would have significant public health significance, through a decrease in fetal and neonatal HDFN morbidity and mortality. Long term goals of this project include translating successful murine innovative therapies to humans, initially in a transfusion setting and ultimately in a pregnancy setting, usin a bench to bedside and back approach.
描述(由申请方提供):既往妊娠/分娩或既往输血诱导的母体RBC同种异体免疫使发育中的胎儿/新生儿面临胎儿和新生儿贫血和溶血性疾病(HDFN)的风险。每600名婴儿中就有1名有HDFN的风险,没有靶向治疗可为同种免疫孕妇提供,也没有针对非D抗原的预防性治疗。靶向疗法的缺乏部分是由于人们不愿意在孕妇或胎儿身上测试创新疗法,这是可以理解的。为了解决这个问题,我们已经开发了我们认为是第一个HDFN动物模型,其中妊娠/分娩能够刺激母体同种免疫,并且这些母体抗体导致HDFN。该模型涉及HDFN(KEL)中高度相关的人抗原的RBC特异性表达的事实进一步增加了其创新。作为我们的R21开发和表征该模型的扩展,我们现在建议利用该模型以损伤控制方式保护发育中的胎儿免受现有母体同种抗体的影响,并以预防性方式防止初级抗KEL形成。中心假设:母体抗RBC同种抗体对胎儿和新生儿的危害可以通过主动或被动的母体免疫调节治疗来预防。具体目标1:研究策略,以尽量减少现有的母体抗KEL同种抗体对发育中的胎儿和新生儿的危险。具体目标2:研究预防妊娠/分娩期间原发性抗KEL RBC同种异体免疫的策略。具体目标3:研究其他(非KEL)RBC同种抗体对发育中胎儿和新生儿的影响。公共卫生意义/长期目标:通过降低胎儿和新生儿HDFN发病率和死亡率,开发靶向治疗以最大限度地降低现有RBC同种抗体的危险或预防携带表达同源RBC抗原的胎儿的女性进行初次同种免疫,将具有显著的公共卫生意义。该项目的长期目标包括将成功的鼠创新疗法转化为人类,最初在输血环境中,最终在妊娠环境中,使用从工作台到床边和背部的方法。

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)

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JEANNE E HENDRICKSON其他文献

JEANNE E HENDRICKSON的其他文献

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{{ truncateString('JEANNE E HENDRICKSON', 18)}}的其他基金

The Mouse Blood Center Core
小鼠血液中心核心
  • 批准号:
    10192791
  • 财政年份:
    2017
  • 资助金额:
    $ 42.28万
  • 项目类别:
Enrichment Core
浓缩核心
  • 批准号:
    10060460
  • 财政年份:
    2015
  • 资助金额:
    $ 42.28万
  • 项目类别:
Enrichment Core
浓缩核心
  • 批准号:
    10249345
  • 财政年份:
    2015
  • 资助金额:
    $ 42.28万
  • 项目类别:
Enrichment Core
浓缩核心
  • 批准号:
    10677854
  • 财政年份:
    2015
  • 资助金额:
    $ 42.28万
  • 项目类别:
Enrichment Core
浓缩核心
  • 批准号:
    10624203
  • 财政年份:
    2015
  • 资助金额:
    $ 42.28万
  • 项目类别:
Protecting Fetuses and Newborns from Maternal RBC Alloantibodies
保护胎儿和新生儿免受母体红细胞同种抗体的影响
  • 批准号:
    9285613
  • 财政年份:
    2014
  • 资助金额:
    $ 42.28万
  • 项目类别:
Protecting Fetuses and Newborns from Maternal RBC Alloantibodies
保护胎儿和新生儿免受母体红细胞同种抗体的影响
  • 批准号:
    8672242
  • 财政年份:
    2014
  • 资助金额:
    $ 42.28万
  • 项目类别:
Immunoprophylaxis to Kell RBC Alloimmunization During Pregnancy
怀孕期间凯尔红细胞同种免疫的免疫预防
  • 批准号:
    8866087
  • 财政年份:
    2012
  • 资助金额:
    $ 42.28万
  • 项目类别:
Immunoprophylaxis to Kell RBC Alloimmunization During Pregnancy
怀孕期间凯尔红细胞同种免疫的免疫预防
  • 批准号:
    8351014
  • 财政年份:
    2012
  • 资助金额:
    $ 42.28万
  • 项目类别:
Immunoprophylaxis to Kell RBC Alloimmunization During Pregnancy
怀孕期间凯尔红细胞同种免疫的免疫预防
  • 批准号:
    8531342
  • 财政年份:
    2012
  • 资助金额:
    $ 42.28万
  • 项目类别:

相似海外基金

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
  • 批准号:
    10711667
  • 财政年份:
    2023
  • 资助金额:
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  • 项目类别:
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  • 批准号:
    10711670
  • 财政年份:
    2023
  • 资助金额:
    $ 42.28万
  • 项目类别:
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:
    $ 42.28万
  • 项目类别:
Basic and Translational Mechanisms of Alloimmunization to RBC Transfusion. Project 2
红细胞输注同种免疫的基本和转化机制。
  • 批准号:
    10711669
  • 财政年份:
    2023
  • 资助金额:
    $ 42.28万
  • 项目类别:
Basic and Translational Mechanisms of Alloimmunization to RBC Transfusion. Project 1
红细胞输注同种免疫的基本和转化机制。
  • 批准号:
    10711668
  • 财政年份:
    2023
  • 资助金额:
    $ 42.28万
  • 项目类别:
Basic and Translational Mechanisms of Alloimmunization to RBC Transfusion
红细胞输注同种免疫的基本机制和转化机制
  • 批准号:
    10711666
  • 财政年份:
    2023
  • 资助金额:
    $ 42.28万
  • 项目类别:
Examining Immune Circuits Responsible for Anamnestic RBC Alloimmunization
检查负责记忆性红细胞同种免疫的免疫回路
  • 批准号:
    10641025
  • 财政年份:
    2022
  • 资助金额:
    $ 42.28万
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镰状细胞病中自身抗体诱导的 1 型干扰素和红细胞同种免疫
  • 批准号:
    10642866
  • 财政年份:
    2022
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    $ 42.28万
  • 项目类别:
Examining Immune Circuits Responsible for Anamnestic RBC Alloimmunization
检查负责记忆性红细胞同种免疫的免疫回路
  • 批准号:
    10535284
  • 财政年份:
    2022
  • 资助金额:
    $ 42.28万
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Donor and unit factors associated with recipient RBC alloimmunization formation
与受者红细胞同种免疫形成相关的供者和单位因素
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    10515205
  • 财政年份:
    2022
  • 资助金额:
    $ 42.28万
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