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: 10225355
• 负责人: ELAINE F REED
• 金额: $ 152.41万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 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: https://reporter.nih.gov/project-details/10225355
• 关键词: Allografting; Antibody-Dependent Enhancement; Area; B cell repertoire; Biological Markers; Biometry; Biopsy Specimen; Blood; Cell physiology; Cells; Chronic; Clinical; Collection; Complex; Computer Models; Coupled; Cytomegalovirus; Cytomegalovirus Infections; Cytometry; Cytotoxic T-Lymphocytes; Data; Development; Disease; Enrollment; Equilibrium; Evolution; Family; Frequencies; Functional disorder; Gene Expression Profile; Generations; Genetic Transcription; Goals; Graft Rejection; Herpesviridae; Human; Humoral Immunities; Immune; Immune Evasion; Immune response; Immune system; Immunity; Immunocompetent; Immunocompromised Host; Immunology; Immunophenotyping; Infection; Inflammation; Injury; Innate Immune Response; KLRD1 gene; Kidney Transplantation; Kinetics; Maps; Molecular; Morbidity - disease rate; Natural Killer Cells; Organ; Organ Transplantation; Outcome; Patients; Peripheral; Persons; Population; Primary Infection; Receptor Cell; Research; Research Personnel; Resources; Risk; Risk Assessment; Role; Sampling; Seroprevalences; Severities; Solid; Standardization; Stem cell transplant; Symptoms; System; Systems Analysis; Systems Biology; T-Lymphocyte; Technology; Transplant Recipients; Transplantation; Urine; Vaccination; Vaccines; Viral; Virus; Virus Diseases; Whole Blood; Work; adaptive immune response; allograft rejection; antibody-dependent cell cytotoxicity; clinical phenotype; high throughput screening; insight; isoimmunity; member; mortality; non-invasive monitor; novel; novel strategies; pathogen; receptor; response; senescence; transmission process

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.

总体而言：肾移植受者的免疫应答与巨细胞病毒的对应关系 摘要/摘要 巨细胞病毒(CMV)是疱疹病毒家族的成员之一，已与人类一起进化了数千年 多年来，潜伏期、免疫逃避和传播之间存在复杂的平衡。而多达70%的人类 全世界都有CMV感染的证据，某些地区的血清阳性率接近100%，健康 人们很少或根本没有表现出主要感染的临床症状。巨细胞病毒病在免疫学中很少见 由于先天免疫反应和自然杀伤细胞(NK)和T细胞的持续监视而产生的合格宿主 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 实体器官和干细胞移植后免疫功能受损的宿主，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的先天免疫和获得性免疫反应。 在使用高通量系统生物学方法的免疫受损的实体器官移植接受者中， 精心挑选的临床表型和新的统计和计算方法：a)先天特征 和获得性免疫反应，并确定CMV感染对 同种异体免疫反应和移植排斥反应的发展；b)确定NK细胞在巨细胞病毒中的作用 再激活和慢性移植排斥反应和c)定义巨细胞病毒感染对发展的影响。 慢性移植物损伤。这项拟议研究的长期目标是开发一张详细的分子图谱 初发和潜伏巨细胞病毒感染的先天性和获得性免疫反应之间的相互作用 移植受者。对病毒与免疫系统相互作用的详细见解将产生 关于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 并明确巨细胞病毒感染和器官移植损伤之间的相互作用。

项目成果

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: Frontiers in immunology
• 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: American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
• 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: Proceedings of the National Academy of Sciences of the United States of America
• 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: NPJ vaccines
• 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: Transplantation direct
• 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