1.Donor-derived cell-free DNA-based liquid biopsies to determine future kidney transplant rejection
Weiwei WANG ; Cuello Garcia HAIDER ; Yinfeng WANG ; Zhoufan ZHANG ; Yuelin LIU ; Fengcheng XUE ; Haitao LIU ; Tingya JIANG ; Jingyi CAO ; Yang ZHOU
Kidney Research and Clinical Practice 2025;44(5):705-725
Donor-derived cell-free DNA (dd-cfDNA) based liquid kidney biopsies have the potential to detect the chances of kidney transplant rejection. Several studies have found that dd-cfDNA can be used to determine the risk of kidney transplant rejection and may correlate with antibody-mediated rejection (ABMR), T cell-mediated rejection (TCMR), and estimated glomerular filtration rate (eGFR). A high concentration of dd-cfDNA in the body fluids may indicate possible transplant rejection since dd-cfDNA is released as a result of apoptotic and necrotic processes initiated by the recipient’s immune system. dd-cfDNA assays have advantages over conventional biopsies since they are noninvasive, and therefore, have the potential to provide a safe and reliable biomarker. Different dd-cfDNA levels have been reported above a number of cutoff thresholds: ABMR at 2.45% and TCMR at 1.3%, compared with 0.44% in healthy patients; and eGFR at 2.5%, a decrease of 25% compared with healthy patients. These results indicate the levels of dd-cfDNA that may be used to signal possible kidney rejection. dd-cfDNA assay is a rapid technique, making it particularly useful in emergencies, and further research into its use in the study of kidney rejection should prove beneficial.
2.Urinary donor-derived cell-free DNA as a non-invasive biomarker for BK polyomavirus-associated nephropathy.
Jia SHEN ; Luying GUO ; Wenhua LEI ; Shuaihui LIU ; Pengpeng YAN ; Haitao LIU ; Jingyi ZHOU ; Qin ZHOU ; Feng LIU ; Tingya JIANG ; Huiping WANG ; Jianyong WU ; Jianghua CHEN ; Rending WANG
Journal of Zhejiang University. Science. B 2021;22(11):917-928
BK polyomavirus-associated nephropathy (BKPyVAN) is a common cause of allograft failure. However, differentiation between BKPyVAN and type I T cell-mediated rejection (TCMR) is challenging when simian virus 40 (SV40) staining is negative, because of the similarities in histopathology. This study investigated whether donor-derived cell-free DNA (ddcfDNA) can be used to differentiate BKPyVAN. Target region capture sequencing was applied to detect the ddcfDNAs of 12 recipients with stable graft function, 22 with type I TCMR, 21 with proven BKPyVAN, and 5 with possible PyVAN. We found that urinary ddcfDNA levels were upregulated in recipients with graft injury, whereas plasma ddcfDNA levels were comparable for all groups. The median urinary concentrations and fractions of ddcfDNA in proven BKPyVAN recipients were significantly higher than those in type I TCMR recipients (10.4 vs. 6.1 ng/mL,
3.Application of chimeric antigen receptor-regulatory T cell immunotherapy in organ transplantation
Yu WU ; Peilu LI ; Jun GE ; Tingya JIANG
Organ Transplantation 2020;11(5):547-
Regulatory T cell (Treg) is a subset of T cells that negatively regulates immunity and has the function of inhibiting rejection. The specific modification of Treg by chimeric antigen receptor (CAR) technology can successfully chime donor-specific antigen onto the surface of Treg, thus regulating the immune function of the body in a real-time manner. It provides a novel and promising therapeutic option for inducing immune tolerance. In this article, research progresses on Treg in immune related diseases, main difficulties in the realization of CAR-Treg technology and its role in inducing transplantation immune tolerance were reviewed, and the opportunities and challenges of CAR-Treg application in the field of organ transplantation are prospected.

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