PMID- 36081515 OWN - NLM STAT- MEDLINE DCOM- 20220913 LR - 20221107 IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 13 DP - 2022 TI - Immune tolerance induced by hematopoietic stem cell infusion after HLA identical sibling kidney transplantation. PG - 995243 LID - 10.3389/fimmu.2022.995243 [doi] LID - 995243 AB - 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 Steroids were withdrawn after 1 year, and 0.5 mg tacrolimus twice a day is currently the only immunosuppression at 8 years and 8 months.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. CI - Copyright (c) 2022 Huang, Shen, Zhou, Yang, Cai, Shen, Feng, Xie, Jiang and Chen. FAU - Huang, Hongfeng AU - Huang H AD - Kidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University School of Medicine, Hangzhou, China. AD - Key Laboratory of Nephropathy, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China. AD - Institute of Nephropathy, Zhejiang University, Hangzhou, China. FAU - Shen, Qixia AU - Shen Q AD - Kidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University School of Medicine, Hangzhou, China. AD - Key Laboratory of Nephropathy, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China. AD - Institute of Nephropathy, Zhejiang University, Hangzhou, China. FAU - Zhou, Jingyi AU - Zhou J AD - Kidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University School of Medicine, Hangzhou, China. AD - Key Laboratory of Nephropathy, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China. AD - Institute of Nephropathy, Zhejiang University, Hangzhou, China. FAU - Yang, Xiuyan AU - Yang X AD - Kidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University School of Medicine, Hangzhou, China. AD - Key Laboratory of Nephropathy, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China. AD - Institute of Nephropathy, Zhejiang University, Hangzhou, China. FAU - Cai, Qiuqin AU - Cai Q AD - Kidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University School of Medicine, Hangzhou, China. AD - Key Laboratory of Nephropathy, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China. AD - Institute of Nephropathy, Zhejiang University, Hangzhou, China. FAU - Shen, Jia AU - Shen J AD - Kidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University School of Medicine, Hangzhou, China. AD - Key Laboratory of Nephropathy, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China. AD - Institute of Nephropathy, Zhejiang University, Hangzhou, China. FAU - Feng, Shi AU - Feng S AD - Kidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University School of Medicine, Hangzhou, China. AD - Key Laboratory of Nephropathy, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China. AD - Institute of Nephropathy, Zhejiang University, Hangzhou, China. FAU - Xie, Wenqing AU - Xie W AD - Kidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University School of Medicine, Hangzhou, China. AD - Key Laboratory of Nephropathy, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China. FAU - Jiang, Hong AU - Jiang H AD - Kidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University School of Medicine, Hangzhou, China. AD - Key Laboratory of Nephropathy, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China. AD - Institute of Nephropathy, Zhejiang University, Hangzhou, China. FAU - Chen, Jianghua AU - Chen J AD - Kidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University School of Medicine, Hangzhou, China. AD - Key Laboratory of Nephropathy, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China. AD - Institute of Nephropathy, Zhejiang University, Hangzhou, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220823 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 RN - 0 (HLA Antigens) SB - IM EIN - Front Immunol. 2022 Oct 19;13:1052676. PMID: 36341386 MH - *Graft vs Host Disease/etiology MH - HLA Antigens MH - *Hematopoietic Stem Cell Transplantation/adverse effects/methods MH - Hematopoietic Stem Cells MH - Humans MH - Immune Tolerance MH - *Kidney Transplantation/adverse effects MH - Siblings PMC - PMC9447861 OTO - NOTNLM OT - GVHD OT - chimerism OT - hematopoietic stem cell infusion OT - immune tolerance OT - immunosuppression withdrawal OT - kidney transplantation COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2022/09/10 06:00 MHDA- 2022/09/14 06:00 PMCR- 2022/01/01 CRDT- 2022/09/09 02:06 PHST- 2022/07/15 00:00 [received] PHST- 2022/08/04 00:00 [accepted] PHST- 2022/09/09 02:06 [entrez] PHST- 2022/09/10 06:00 [pubmed] PHST- 2022/09/14 06:00 [medline] PHST- 2022/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2022.995243 [doi] PST - epublish SO - Front Immunol. 2022 Aug 23;13:995243. doi: 10.3389/fimmu.2022.995243. eCollection 2022.