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：绘制肾移植受者对巨细胞病毒的免疫反应

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