Mapping Immune Responses to CMV in Renal Transplant Recipients
绘制肾移植受者对 CMV 的免疫反应
基本信息
- 批准号:10225355
- 负责人:
- 金额:$ 152.41万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2017
- 资助国家:美国
- 起止时间:2017-08-01 至 2024-07-31
- 项目状态:已结题
- 来源:
- 关键词:AllograftingAntibody-Dependent EnhancementAreaB cell repertoireBiological MarkersBiometryBiopsy SpecimenBloodCell physiologyCellsChronicClinicalCollectionComplexComputer ModelsCoupledCytomegalovirusCytomegalovirus InfectionsCytometryCytotoxic T-LymphocytesDataDevelopmentDiseaseEnrollmentEquilibriumEvolutionFamilyFrequenciesFunctional disorderGene Expression ProfileGenerationsGenetic TranscriptionGoalsGraft RejectionHerpesviridaeHumanHumoral ImmunitiesImmuneImmune EvasionImmune responseImmune systemImmunityImmunocompetentImmunocompromised HostImmunologyImmunophenotypingInfectionInflammationInjuryInnate Immune ResponseKLRD1 geneKidney TransplantationKineticsMapsMolecularMorbidity - disease rateNatural Killer CellsOrganOrgan TransplantationOutcomePatientsPeripheralPersonsPopulationPrimary InfectionReceptor CellResearchResearch PersonnelResourcesRiskRisk AssessmentRoleSamplingSeroprevalencesSeveritiesSolidStandardizationStem cell transplantSymptomsSystemSystems AnalysisSystems BiologyT-LymphocyteTechnologyTransplant RecipientsTransplantationUrineVaccinationVaccinesViralVirusVirus DiseasesWhole BloodWorkadaptive immune responseallograft rejectionantibody-dependent cell cytotoxicityclinical phenotypehigh throughput screeninginsightisoimmunitymembermortalitynon-invasive monitornovelnovel strategiespathogenreceptorresponsesenescencetransmission process
项目摘要
OVERALL: Mapping Immune Reponses to CMV in Renal Transplant Recipients
SUMMARY/ABSTRACT
Cytomegalovirus (CMV), a member of the Herpes virus family, has evolved alongside humans for thousands of
years with a complex balance of latency, immune evasion, and transmission. While up to 70% of humans
worldwide have evidence of CMV infection and seroprevalence approaches 100% in certain areas, healthy
people show little to no clinical symptoms of primary infection. CMV disease is rarely observed in immune
competent hosts because of innate immune responses and constant surveillance by natural killer (NK) and T
cells that cooperatively control CMV. However, CMV is one of the most problematic pathogens in the
immunocompromised host, after solid organ and stem cell transplantation causing increased risk of graft
dysfunction, mortality and graft loss. We propose to study the innate and adaptive immune responses to CMV
in immunocompromised solid organ transplant recipients using a high-throughput systems biology approach,
carefully curated clinical phenotypes and novel statistical and computational approaches to: a) profile innate
and adaptive immune responses during primary CMV infection and define the effects of CMV infection on the
development of alloimmune responsiveness and transplant rejection; b) determine the role of NK cells in CMV
reactivation and chronic transplant rejection and c) define the effects of CMV infection on the development of
chronic allograft injury. The long-term goal of the proposed research is to develop a detailed molecular map of
the cross-talk between the innate and adaptive immune response in primary and latent CMV infection in the
transplant recipient. Detailed insights into the interaction of the virus with the immune system stand to generate
concepts for more adequate vaccine strategies, risk assessment for CMV infection to better understand the
immune system and to define the interplay of CMV infection and organ transplant injury.
总体:肾移植受者对CMV的免疫应答图谱
总结/摘要
巨细胞病毒(CMV)是疱疹病毒家族的一员,已经与人类一起进化了数千年。
潜伏期、免疫逃避和传播的复杂平衡。而高达70%的人类
世界范围内有证据表明CMV感染和血清阳性率接近100%,在某些地区,健康
人们几乎没有表现出原发性感染的临床症状。CMV疾病在免疫系统中很少观察到。
由于先天免疫应答和自然杀伤细胞(NK)和T细胞的持续监视,
协同控制CMV的细胞。然而,CMV是世界上最有问题的病原体之一。
免疫功能低下的宿主,在实体器官和干细胞移植后导致移植风险增加
功能障碍、死亡率和移植物丢失。我们建议研究CMV的先天性和适应性免疫应答
在使用高通量系统生物学方法的免疫受损实体器官移植接受者中,
精心策划的临床表型和新的统计和计算方法,以:
和适应性免疫反应,并确定CMV感染对免疫功能的影响。
同种免疫应答和移植排斥的发展; B)确定NK细胞在CMV中的作用
c)确定CMV感染对CMV再激活和慢性移植排斥的影响,
慢性同种异体移植物损伤拟议研究的长期目标是开发一个详细的分子图谱,
原发性和潜伏性CMV感染中先天性和适应性免疫应答之间的相互作用,
移植受体深入了解病毒与免疫系统的相互作用,
更充分的疫苗策略的概念,CMV感染的风险评估,以更好地了解
免疫系统,并确定CMV感染和器官移植损伤的相互作用。
项目成果
期刊论文数量(27)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Acute and Chronic Changes in Gene Expression After CMV DNAemia in Kidney Transplant Recipients.
- DOI:10.3389/fimmu.2021.750659
- 发表时间:2021
- 期刊:
- 影响因子:7.3
- 作者:Ahn R;Schaenman J;Qian Z;Pickering H;Groysberg V;Rossetti M;Llamas M;Hoffmann A;Gjertson D;Deng M;Bunnapradist S;Reed EF;CMV Systems Immunobiology Group
- 通讯作者:CMV Systems Immunobiology Group
Antibody-induced vascular inflammation skews infiltrating macrophages to a novel remodeling phenotype in a model of transplant rejection.
- DOI:10.1111/ajt.15934
- 发表时间:2020-10
- 期刊:
- 影响因子:0
- 作者:Wei X;Valenzuela NM;Rossetti M;Sosa RA;Nevarez-Mejia J;Fishbein GA;Mulder A;Dhar J;Keslar KS;Baldwin WM 3rd;Fairchild RL;Hou J;Reed EF
- 通讯作者:Reed EF
Mass cytometry reveals single-cell kinetics of cytotoxic lymphocyte evolution in CMV-infected renal transplant patients.
- DOI:10.1073/pnas.2116588119
- 发表时间:2022-02-22
- 期刊:
- 影响因子:11.1
- 作者:Ishiyama K;Arakawa-Hoyt J;Aguilar OA;Damm I;Towfighi P;Sigdel T;Tamaki S;Babdor J;Spitzer MH;Reed EF;Sarwal MM;Lanier LL;CMV Systems Immunobiology Group
- 通讯作者:CMV Systems Immunobiology Group
Synthetic multiantigen MVA vaccine COH04S1 protects against SARS-CoV-2 in Syrian hamsters and non-human primates.
- DOI:10.1038/s41541-022-00436-6
- 发表时间:2022-01-21
- 期刊:
- 影响因子:9.2
- 作者:Chiuppesi F;Nguyen VH;Park Y;Contreras H;Karpinski V;Faircloth K;Nguyen J;Kha M;Johnson D;Martinez J;Iniguez A;Zhou Q;Kaltcheva T;Frankel P;Kar S;Sharma A;Andersen H;Lewis MG;Shostak Y;Wussow F;Diamond DJ
- 通讯作者:Diamond DJ
DNA Methylation Age Is More Closely Associated With Infection Risk Than Chronological Age in Kidney Transplant Recipients.
- DOI:10.1097/txd.0000000000001020
- 发表时间:2020-08
- 期刊:
- 影响因子:2.3
- 作者:Schaenman J;Zhou X;Guo R;Rossetti M;Liang EC;Lum E;Abdalla B;Bunnapradist S;Pham PT;Danovitch G;Karlamangla A;Reed E;Horvath S;Elashoff D
- 通讯作者:Elashoff D
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{{ truncateString('ELAINE F REED', 18)}}的其他基金
Human Immunomics & Trained Immunity in Persistent Candidemia
人类免疫组学
- 批准号:
10551710 - 财政年份:2023
- 资助金额:
$ 152.41万 - 项目类别:
Targeting YAP with statins to prevent antibody-mediated transplant rejection
用他汀类药物靶向 YAP 预防抗体介导的移植排斥
- 批准号:
10320048 - 财政年份:2020
- 资助金额:
$ 152.41万 - 项目类别:
The role of HLA and its coreceptors in endothelial cell activation and leukocyte recruitment in antibody-mediated transplant rejection
HLA 及其辅助受体在抗体介导的移植排斥中内皮细胞激活和白细胞募集中的作用
- 批准号:
10231220 - 财政年份:2018
- 资助金额:
$ 152.41万 - 项目类别:
The role of HLA and its coreceptors in endothelial cell activation and leukocyte recruitment in antibody-mediated transplant rejection
HLA 及其辅助受体在抗体介导的移植排斥中内皮细胞激活和白细胞募集中的作用
- 批准号:
10462514 - 财政年份:2018
- 资助金额:
$ 152.41万 - 项目类别:
Mapping Immune Responses to CMV in Renal Transplant Recipients - Transplant Supplement
绘制肾移植受者对 CMV 的免疫反应 - Transplant Supplement
- 批准号:
10225673 - 财政年份:2017
- 资助金额:
$ 152.41万 - 项目类别:
Mapping Immune Responses to CMV in Renal Transplant Recipients
绘制肾移植受者对 CMV 的免疫反应
- 批准号:
10000838 - 财政年份:2017
- 资助金额:
$ 152.41万 - 项目类别:
Ischemia-Reperfusion Injury in Human Liver Transplantation: Reciprocal Regulation of Innate/Adaptive Immune Responses
人肝移植中的缺血再灌注损伤:先天/适应性免疫反应的相互调节
- 批准号:
9975701 - 财政年份:2017
- 资助金额:
$ 152.41万 - 项目类别:
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