Successful Induction of Specific Immunological Tolerance by Combined Kidney and Hematopoietic Stem Cell Transplantation in HLA-Identical Siblings
FRONTIERS IN IMMUNOLOGY(2022)
摘要
Induction of immunological tolerance has been the holy grail of transplantation immunology for decades. The only successful approach to achieve it in patients has been a combined kidney and hematopoietic stem cell transplantation from an HLA-matched or -mismatched living donor. Here, we report the first three patients in Europe included in a clinical trial aiming at the induction of tolerance by mixed lymphohematopoietic chimerism after kidney transplantation. Two female and one male patient were transplanted with a kidney and peripherally mobilized hematopoietic stem cells from their HLA-identical sibling donor. The protocol followed previous studies at Stanford University: kidney transplantation was performed on day 0 including induction with anti-thymocyte globulin followed by conditioning with 10x 1.2 Gy total lymphoid irradiation and the transfusion of CD34+ cells together with a body weight-adjusted dose of donor T cells on day 11. Immunosuppression consisted of cyclosporine A and steroids for 10 days, cyclosporine A and mycophenolate mofetil for 1 month, and then cyclosporine A monotherapy with tapering over 9-20 months. The 3 patients have been off immunosuppression for 4 years, 19 months and 8 months, respectively. No rejection or graft-versus-host disease occurred. Hematological donor chimerism was stable in the first, but slowly declining in the other two patients. A molecular microscope analysis in patient 2 revealed the genetic profile of a normal kidney. No relevant infections were observed, and the quality of life in all three patients is excellent. During the SARS-CoV-2 pandemic, all three patients were vaccinated with the mRNA vaccine BNT162b2 (Comirnaty(R)), and they showed excellent humoral and in 2 out 3 patients also cellular SARS-CoV-2-specific immunity. Thus, combined kidney and hematopoietic stem cell transplantation is a feasible and successful approach to induce specific immunological tolerance in the setting of HLA-matched sibling living kidney donation while maintaining immune responsiveness to an mRNA vaccine (ClinicalTrials.gov: NCT00365846).
更多查看译文
关键词
chimerism, hematopoietic stem cell transplantation (HSCT), tolerance, kidney transplantation, immunocompetence, COVID, 19
AI 理解论文
溯源树
样例
生成溯源树,研究论文发展脉络
Chat Paper
正在生成论文摘要