Frontiers in Immunology (Aug 2022)

Immune tolerance induced by hematopoietic stem cell infusion after HLA identical sibling kidney transplantation

  • 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

DOI
https://doi.org/10.3389/fimmu.2022.995243
Journal volume & issue
Vol. 13

Abstract

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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 Steroids were withdrawn after 1 year, and 0.5 mg tacrolimus twice a day is currently the only immunosuppression at 8 years and 8 months.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.

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