Accommodation in Transplantation

移植住宿

基本信息

批准号：
9231910
负责人：
MARILIA Isabel CASCALHO
金额：
$ 38.75万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-04-06 至 2018-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9231910
关键词：
Acute Address Antibodies Antibody Response Antigens Attention Avidity B-Lymphocytes Biological Biological Assay Biopsy Blood Blood Circulation Blood typing procedure Cells Characteristics Chronic Clinical Complement Detection Diagnosis Donor person Exhibits Exposure to Frequencies Genes Goals Gold Health Immune Immune response Immunity Immunoglobulin Variable Region Immunoglobulin-Secreting Cells Inflammation Inflammatory Injury Intervention Investigation Kidney Kidney Transplantation MHC antigen Mediating Mutation Natural Immunity Organ Organ Transplantation Outcome Pathology Pathway interactions Phagocytes Prevalence Property Protocols documentation Reporting Research Resistance Rest Risk Specificity Testing Therapeutic Time Tissues Transplant Recipients Transplantation adaptive immunity assault blood group cancer cell cancer transplantation conditioning enzyme linked immunospot assay experience graft failure graft function interest microorganism novel strategies peripheral blood response variable region gene

项目摘要

DESCRIPTION (provided by applicant): Kidney transplantation elicits powerful B cell responses, which generate antibodies specific for the transplant donor. Donor-specific antibodies can cause acute and chronic rejection and sometimes graft failure. However, donor-specific antibodies are sometimes detected in recipients who lack any evidence of rejection. In this setting, donor-specific antibodies appear to evoke resistance to immune and inflammatory injury instead of rejection. The pathways that enable tissues and organs to accommodate to immunity and inflammation have been studied extensively. But, how a B cell response generates accommodation instead of rejection is not known. The proposed research will address this overarching question in kidney transplant recipients who are tested for donor-specific antibodies and undergo three "protocol" biopsies during the first year. As a first objective, B cell responses specific for kidney transplant donors will be identified by testing for donor-specific antibodies in blood; but, also by determining the frequency and isotype of donor-specific antibody-secreting cells in blood (because donor-specific antibodies can be substantially absorbed by functioning organ grafts). B cell responses will be interpreted in the light of findings in "protocol" biopsies to help determine whether a response reflects accommodation or rejection. As a second objective, frequency of mutations in Ig variable region genes and the avidity and range of specificities of the encoded antibodies from donor-specific B cells in accommodation and rejection will be compared. The results of this project will indicate whether accommodation is a common outcome of kidney transplantation. Further, distinct facets of B cell responses in accommodation versus rejection could point to novel approaches to assessing risk and even new targets for biological intervention in transplantation, cancer and other conditions.

描述（由申请人提供）：肾移植会引发强大的 B 细胞反应，产生针对移植供体的特异性抗体，可导致急性和慢性排斥反应，有时甚至会导致移植失败。然而，有时会在受者体内检测到供体特异性抗体。在这种情况下，供体特异性抗体似乎会引起对免疫和炎症损伤的抵抗力，而不是排斥反应，但是，如何使组织和器官适应免疫和炎症已经得到了广泛的研究。 B 细胞反应产生调节拟议的研究将解决肾移植受者的这一首要问题，这些受者将在第一年接受捐献者特异性抗体检测并进行三次“方案”活检。移植捐献者将通过测试来确定血液中的供体特异性抗体；但是，还可以通过确定血液中供体特异性抗体分泌细胞的频率和同种型（因为供体特异性抗体可以被功能性器官移植物充分吸收），从而在 B 细胞反应中进行解释。根据“方案”活检的结果，帮助确定反应是否反映了适应性调节或排斥。住宿和拒绝将该项目的结果将表明适应是否是肾移植的常见结果。此外，适应与排斥的 B 细胞反应的不同方面可能会指出评估风险的新方法，甚至是移植中生物干预的新目标。癌症和其他疾病。

项目成果

期刊论文数量（4）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Accommodation and related conditions in vascularized composite allografts.

血管化复合同种异体移植物的调节和相关条件。

DOI：
发表时间：
2017-10
期刊：
影响因子：
0
作者：
Platt, Jeffrey L;Kaufman, Christina L;Garcia de Mattos Barbosa, Mayara;Cascalho, Marilia
通讯作者：
Cascalho, Marilia

The role of B cell immunity in VCA graft rejection and acceptance.

B 细胞免疫在 VCA 移植物排斥和接受中的作用。

DOI：
发表时间：
2019-06
期刊：
影响因子：
2.7
作者：
Kaufman, Christina L;Cascalho, Marilia;Ozyurekoglu, Tuna;Jones, Christopher M;Ramirez, Allan;Roberts, Tiffany;Tien, Huey Y;Moreno, Rodrigo;Galvis, Elkin;Tsai, Tsu;Palazzo, Michelle;Farner, Scott;Platt, Jeffrey L
通讯作者：
Platt, Jeffrey L

Restoring Ovarian Endocrine Function with Encapsulated Ovarian Allograft in Immune Competent Mice.

用封装的同种异体卵巢移植物恢复免疫活性小鼠的卵巢内分泌功能。

DOI：
发表时间：
2017-07
期刊：
影响因子：
3.8
作者：
David, Anu;Day, James Ronald;Cichon, Alexa Leigh;Lefferts, Adam;Cascalho, Marilia;Shikanov, Ariella
通讯作者：
Shikanov, Ariella

On Poetry and Vascularized Composite Allografting.

关于诗歌和血管化复合同种异体移植。