Kwon Yeongbeen, Lee Kyo Won, Kim You Min, Park Hyojun, Jung Min Kyung, Choi Young Joon, Son Jin Kyung, Hong JuHee, Park Su-Hyung, Kwon Ghee Young, Yoo Heejin, Kim Kyunga, Kim Sung Joo, Park Jae Berm, Shin Eui-Cheol
Samsung Advanced Institute for Health Sciences & Technology (SAIHST) Graduate School Department of Health Sciences & Technology Sungkyunkwan University Seoul Korea.
Transplantation Research Center Samsung Medical Center Samsung Biomedical Research Institute Seoul Korea.
Clin Transl Immunology. 2021 Aug 9;10(8):e1325. doi: 10.1002/cti2.1325. eCollection 2021.
Simultaneous transplantation of a solid organ and bone marrow from the same donor is a possible means of achieving transplant tolerance. Here, we attempted to identify biomarkers that indicate transplant tolerance for discontinuation of immunosuppressants in combined kidney and bone marrow transplantation (CKBMT).
Conventional kidney transplant (KT) recipients ( = 20) and CKBMT recipients ( = 6) were included in this study. We examined various immunological parameters by flow cytometry using peripheral blood mononuclear cells (PBMCs), including the frequency and phenotype of regulatory T (Treg) cell subpopulations. We also examined the suppressive activity of the Treg cell population in the setting of mixed lymphocyte reaction (MLR) with or without Treg cell depletion.
Among six CKBMT recipients, three successfully discontinued immunosuppressants (tolerant group) and three could not (non-tolerant group). The CD45RAFOXP3 Treg cell subpopulation was expanded in CKBMT recipients compared to conventional kidney transplant patients, and this was more obvious in the tolerant group than the non-tolerant group. In addition, high suppressive activity of the Treg cell population was observed in the tolerant group. The ratio of CD45RAFOXP3 Treg cells to CD45RAFOXP3 cells indicated good discrimination between the tolerant and non-tolerant groups.
Thus, our findings propose a biomarker that can distinguish CKBMT patients who achieve transplant tolerance and are eligible for discontinuation of immunosuppressants and may provide insight into tolerance mechanisms in CKBMT.
同时移植来自同一供体的实体器官和骨髓是实现移植耐受的一种可能方法。在此，我们试图识别出能表明联合肾与骨髓移植（CKBMT）中停用免疫抑制剂后移植耐受情况的生物标志物。
本研究纳入了常规肾移植（KT）受者（n = 20）和CKBMT受者（n = 6）。我们使用外周血单个核细胞（PBMC）通过流式细胞术检测了各种免疫参数，包括调节性T（Treg）细胞亚群的频率和表型。我们还在有或没有Treg细胞耗竭的混合淋巴细胞反应（MLR）环境中检测了Treg细胞群体的抑制活性。
在6名CKBMT受者中，3名成功停用了免疫抑制剂（耐受组），3名未能停用（非耐受组）。与常规肾移植患者相比，CKBMT受者中CD45RAFOXP3 Treg细胞亚群有所扩增，且在耐受组中比非耐受组更为明显。此外，在耐受组中观察到Treg细胞群体具有较高的抑制活性。CD45RAFOXP3 Treg细胞与CD45RAFOXP3细胞的比例显示出在耐受组和非耐受组之间有良好的区分度。
因此，我们的研究结果提出了一种生物标志物，它可以区分实现移植耐受且有资格停用免疫抑制剂的CKBMT患者，并可能为CKBMT中的耐受机制提供见解。
