Accommodation in Transplantation

移植住宿

• 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
• 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

 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.



项目成果

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: 10.1097/mot.0000000000000446
• 发表时间: 2017
• 期刊: Current opinion in organ transplantation
• 影响因子: 2.2
• 作者: Platt,JeffreyL;Kaufman,ChristinaL;GarciadeMattosBarbosa,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: 10.1016/j.humimm.2019.03.002
• 发表时间: 2019
• 期刊: Human immunology
• 影响因子: 2.7
• 作者: Kaufman,ChristinaL;Cascalho,Marilia;Ozyurekoglu,Tuna;Jones,ChristopherM;Ramirez,Allan;Roberts,Tiffany;Tien,HueyY;Moreno,Rodrigo;Galvis,Elkin;Tsai,Tsu-Min;Palazzo,Michelle;Farner,Scott;Platt,JeffreyL
• 通讯作者: Platt,JeffreyL

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

• DOI: 10.1007/s10439-016-1780-6
• 发表时间: 2017-07
• 期刊: Annals of biomedical engineering
• 影响因子: 3.8
• 作者: David A;Day JR;Cichon AL;Lefferts A;Cascalho M;Shikanov A
• 通讯作者: Shikanov A