Immune tolerance induced by hematopoietic stem cell infusion after HLA identical sibling kidney transplantation
After the first attempt to induce operational tolerance, it has taken decades to implement it in clinical practice. Recipients with Human leukocyte antigen (HLA) identical sibling donors were enrolled. Hematopoietic stem cells (HSCs) infusion was done after HLA identical sibling kidney transplantati...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-08-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.995243/full |
| _version_ | 1798029611922096128 |
|---|---|
| author | Hongfeng Huang Hongfeng Huang Hongfeng Huang Qixia Shen Qixia Shen Qixia Shen Jingyi Zhou Jingyi Zhou Jingyi Zhou Xiuyan Yang Xiuyan Yang Xiuyan Yang Qiuqin Cai Qiuqin Cai Qiuqin Cai Jia Shen Jia Shen Jia Shen Shi Feng Shi Feng Shi Feng Wenqing Xie Wenqing Xie Hong Jiang Hong Jiang Hong Jiang Jianghua Chen Jianghua Chen Jianghua Chen |
| author_facet | Hongfeng Huang Hongfeng Huang Hongfeng Huang Qixia Shen Qixia Shen Qixia Shen Jingyi Zhou Jingyi Zhou Jingyi Zhou Xiuyan Yang Xiuyan Yang Xiuyan Yang Qiuqin Cai Qiuqin Cai Qiuqin Cai Jia Shen Jia Shen Jia Shen Shi Feng Shi Feng Shi Feng Wenqing Xie Wenqing Xie Hong Jiang Hong Jiang Hong Jiang Jianghua Chen Jianghua Chen Jianghua Chen |
| author_sort | Hongfeng Huang |
| collection | DOAJ |
| description | After the first attempt to induce operational tolerance, it has taken decades to implement it in clinical practice. Recipients with Human leukocyte antigen (HLA) identical sibling donors were enrolled. Hematopoietic stem cells (HSCs) infusion was done after HLA identical sibling kidney transplantation (KTx). Three cases included were followed up for over 8 years. The perioperative conditioning protocol included anti-CD20, rabbit anti-thymocyte globulin (ATG), total lymphoid irradiation (TLI), and cyclophosphamide. Infusion of CD3+ cells and CD34+ cells was conducted. The withdrawal of immunosuppression was determined by mixed lymphocyte reaction (MLR) and graft biopsy. Case 1 and Case 2 showed persistent chimerism, while chimerism was not detected in Case 3. All three recipients showed a low-level response to donor-specific stimulation. Case 1 and Case 3 met the withdrawal rules at 16 and 32 months after transplantation, respectively. Graft function was stable, and no rejection signs were observed in routine biopsies until 94 and 61 months after transplantation. Case 2 was diagnosed with graft-versus-host disease (GVHD) 9 months after transplantation and recovered after an enhanced immunosuppression therapy. Steroids were withdrawn after 1 year, and 0.5 mg tacrolimus twice a day is currently the only immunosuppression at 8 years and 8 months. In conclusion, our clinical experience indicated the efficacy of non-myeloablative conditioning protocol for tolerance induction in HLA identical patients. Complete chimerism might be a risk factor for GVHD. |
| first_indexed | 2024-04-11T19:28:07Z |
| format | Article |
| id | doaj.art-eb39aa62522f4cf59032530945bf046e |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-11T19:28:07Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-eb39aa62522f4cf59032530945bf046e2022-12-22T04:07:05ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-08-011310.3389/fimmu.2022.995243995243Immune tolerance induced by hematopoietic stem cell infusion after HLA identical sibling kidney transplantationHongfeng Huang0Hongfeng Huang1Hongfeng Huang2Qixia Shen3Qixia Shen4Qixia Shen5Jingyi Zhou6Jingyi Zhou7Jingyi Zhou8Xiuyan Yang9Xiuyan Yang10Xiuyan Yang11Qiuqin Cai12Qiuqin Cai13Qiuqin Cai14Jia Shen15Jia Shen16Jia Shen17Shi Feng18Shi Feng19Shi Feng20Wenqing Xie21Wenqing Xie22Hong Jiang23Hong Jiang24Hong Jiang25Jianghua Chen26Jianghua Chen27Jianghua Chen28Kidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University School of Medicine, Hangzhou, ChinaKey Laboratory of Nephropathy, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, ChinaInstitute of Nephropathy, Zhejiang University, Hangzhou, ChinaKidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University School of Medicine, Hangzhou, ChinaKey Laboratory of Nephropathy, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, ChinaInstitute of Nephropathy, Zhejiang University, Hangzhou, ChinaKidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University School of Medicine, Hangzhou, ChinaKey Laboratory of Nephropathy, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, ChinaInstitute of Nephropathy, Zhejiang University, Hangzhou, ChinaKidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University School of Medicine, Hangzhou, ChinaKey Laboratory of Nephropathy, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, ChinaInstitute of Nephropathy, Zhejiang University, Hangzhou, ChinaKidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University School of Medicine, Hangzhou, ChinaKey Laboratory of Nephropathy, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, ChinaInstitute of Nephropathy, Zhejiang University, Hangzhou, ChinaKidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University School of Medicine, Hangzhou, ChinaKey Laboratory of Nephropathy, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, ChinaInstitute of Nephropathy, Zhejiang University, Hangzhou, ChinaKidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University School of Medicine, Hangzhou, ChinaKey Laboratory of Nephropathy, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, ChinaInstitute of Nephropathy, Zhejiang University, Hangzhou, ChinaKidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University School of Medicine, Hangzhou, ChinaKey Laboratory of Nephropathy, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, ChinaKidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University School of Medicine, Hangzhou, ChinaKey Laboratory of Nephropathy, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, ChinaInstitute of Nephropathy, Zhejiang University, Hangzhou, ChinaKidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University School of Medicine, Hangzhou, ChinaKey Laboratory of Nephropathy, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, ChinaInstitute of Nephropathy, Zhejiang University, Hangzhou, ChinaAfter the first attempt to induce operational tolerance, it has taken decades to implement it in clinical practice. Recipients with Human leukocyte antigen (HLA) identical sibling donors were enrolled. Hematopoietic stem cells (HSCs) infusion was done after HLA identical sibling kidney transplantation (KTx). Three cases included were followed up for over 8 years. The perioperative conditioning protocol included anti-CD20, rabbit anti-thymocyte globulin (ATG), total lymphoid irradiation (TLI), and cyclophosphamide. Infusion of CD3+ cells and CD34+ cells was conducted. The withdrawal of immunosuppression was determined by mixed lymphocyte reaction (MLR) and graft biopsy. Case 1 and Case 2 showed persistent chimerism, while chimerism was not detected in Case 3. All three recipients showed a low-level response to donor-specific stimulation. Case 1 and Case 3 met the withdrawal rules at 16 and 32 months after transplantation, respectively. Graft function was stable, and no rejection signs were observed in routine biopsies until 94 and 61 months after transplantation. Case 2 was diagnosed with graft-versus-host disease (GVHD) 9 months after transplantation and recovered after an enhanced immunosuppression therapy. Steroids were withdrawn after 1 year, and 0.5 mg tacrolimus twice a day is currently the only immunosuppression at 8 years and 8 months. In conclusion, our clinical experience indicated the efficacy of non-myeloablative conditioning protocol for tolerance induction in HLA identical patients. Complete chimerism might be a risk factor for GVHD.https://www.frontiersin.org/articles/10.3389/fimmu.2022.995243/fullhematopoietic stem cell infusionimmune toleranceimmunosuppression withdrawalchimerismGVHDkidney transplantation |
| spellingShingle | Hongfeng Huang Hongfeng Huang Hongfeng Huang Qixia Shen Qixia Shen Qixia Shen Jingyi Zhou Jingyi Zhou Jingyi Zhou Xiuyan Yang Xiuyan Yang Xiuyan Yang Qiuqin Cai Qiuqin Cai Qiuqin Cai Jia Shen Jia Shen Jia Shen Shi Feng Shi Feng Shi Feng Wenqing Xie Wenqing Xie Hong Jiang Hong Jiang Hong Jiang Jianghua Chen Jianghua Chen Jianghua Chen Immune tolerance induced by hematopoietic stem cell infusion after HLA identical sibling kidney transplantation Frontiers in Immunology hematopoietic stem cell infusion immune tolerance immunosuppression withdrawal chimerism GVHD kidney transplantation |
| title | Immune tolerance induced by hematopoietic stem cell infusion after HLA identical sibling kidney transplantation |
| title_full | Immune tolerance induced by hematopoietic stem cell infusion after HLA identical sibling kidney transplantation |
| title_fullStr | Immune tolerance induced by hematopoietic stem cell infusion after HLA identical sibling kidney transplantation |
| title_full_unstemmed | Immune tolerance induced by hematopoietic stem cell infusion after HLA identical sibling kidney transplantation |
| title_short | Immune tolerance induced by hematopoietic stem cell infusion after HLA identical sibling kidney transplantation |
| title_sort | immune tolerance induced by hematopoietic stem cell infusion after hla identical sibling kidney transplantation |
| topic | hematopoietic stem cell infusion immune tolerance immunosuppression withdrawal chimerism GVHD kidney transplantation |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.995243/full |
| work_keys_str_mv | AT hongfenghuang immunetoleranceinducedbyhematopoieticstemcellinfusionafterhlaidenticalsiblingkidneytransplantation AT hongfenghuang immunetoleranceinducedbyhematopoieticstemcellinfusionafterhlaidenticalsiblingkidneytransplantation AT hongfenghuang immunetoleranceinducedbyhematopoieticstemcellinfusionafterhlaidenticalsiblingkidneytransplantation AT qixiashen immunetoleranceinducedbyhematopoieticstemcellinfusionafterhlaidenticalsiblingkidneytransplantation AT qixiashen immunetoleranceinducedbyhematopoieticstemcellinfusionafterhlaidenticalsiblingkidneytransplantation AT qixiashen immunetoleranceinducedbyhematopoieticstemcellinfusionafterhlaidenticalsiblingkidneytransplantation AT jingyizhou immunetoleranceinducedbyhematopoieticstemcellinfusionafterhlaidenticalsiblingkidneytransplantation AT jingyizhou immunetoleranceinducedbyhematopoieticstemcellinfusionafterhlaidenticalsiblingkidneytransplantation AT jingyizhou immunetoleranceinducedbyhematopoieticstemcellinfusionafterhlaidenticalsiblingkidneytransplantation AT xiuyanyang immunetoleranceinducedbyhematopoieticstemcellinfusionafterhlaidenticalsiblingkidneytransplantation AT xiuyanyang immunetoleranceinducedbyhematopoieticstemcellinfusionafterhlaidenticalsiblingkidneytransplantation AT xiuyanyang immunetoleranceinducedbyhematopoieticstemcellinfusionafterhlaidenticalsiblingkidneytransplantation AT qiuqincai immunetoleranceinducedbyhematopoieticstemcellinfusionafterhlaidenticalsiblingkidneytransplantation AT qiuqincai immunetoleranceinducedbyhematopoieticstemcellinfusionafterhlaidenticalsiblingkidneytransplantation AT qiuqincai immunetoleranceinducedbyhematopoieticstemcellinfusionafterhlaidenticalsiblingkidneytransplantation AT jiashen immunetoleranceinducedbyhematopoieticstemcellinfusionafterhlaidenticalsiblingkidneytransplantation AT jiashen immunetoleranceinducedbyhematopoieticstemcellinfusionafterhlaidenticalsiblingkidneytransplantation AT jiashen immunetoleranceinducedbyhematopoieticstemcellinfusionafterhlaidenticalsiblingkidneytransplantation AT shifeng immunetoleranceinducedbyhematopoieticstemcellinfusionafterhlaidenticalsiblingkidneytransplantation AT shifeng immunetoleranceinducedbyhematopoieticstemcellinfusionafterhlaidenticalsiblingkidneytransplantation AT shifeng immunetoleranceinducedbyhematopoieticstemcellinfusionafterhlaidenticalsiblingkidneytransplantation AT wenqingxie immunetoleranceinducedbyhematopoieticstemcellinfusionafterhlaidenticalsiblingkidneytransplantation AT wenqingxie immunetoleranceinducedbyhematopoieticstemcellinfusionafterhlaidenticalsiblingkidneytransplantation AT hongjiang immunetoleranceinducedbyhematopoieticstemcellinfusionafterhlaidenticalsiblingkidneytransplantation AT hongjiang immunetoleranceinducedbyhematopoieticstemcellinfusionafterhlaidenticalsiblingkidneytransplantation AT hongjiang immunetoleranceinducedbyhematopoieticstemcellinfusionafterhlaidenticalsiblingkidneytransplantation AT jianghuachen immunetoleranceinducedbyhematopoieticstemcellinfusionafterhlaidenticalsiblingkidneytransplantation AT jianghuachen immunetoleranceinducedbyhematopoieticstemcellinfusionafterhlaidenticalsiblingkidneytransplantation AT jianghuachen immunetoleranceinducedbyhematopoieticstemcellinfusionafterhlaidenticalsiblingkidneytransplantation |