Integration of Donor-derived Cell-free DNA With HLA-DR+TNFR2+ Regulatory T Cell in the Prediction of Acute Rejection and Graft Function After Kidney Transplantation
Loma Linda University
Summary
Acute rejection after kidney transplantation should ideally be diagnosed prior to immunologic injury in a non-invasive fashion in order to improve long-term graft function. Donor-derived cell-free DNA (ddcfDNA) is a promising method to do so as it is elevated prior to acute rejection and has good predictive performance especially for antibody-mediated and high severity T-cell mediated rejection. Its ability to predict low severity T-cell mediated rejection and future graft function remains equivocal. Regulatory T cells (Tregs) are essential in transplant tolerance by suppressing effector immune responses. Circulating post-transplant highly suppressive HLA-DR+ Tregs were reduced in recipients who developed acute rejection. Preliminary results in a cohort including predominantly low severity T-cell mediated rejection also showed that pre-transplant circulating highly suppressive TNFR2+ Tregs were reduced in and could predict acute rejection. Integrating dd-cfDNA with HLA-DR+TNFR2+ Treg could improve the predictive performance for acute rejection especially of low severity and potentially predict graft function. Plasma dd-cfDNA and HLA-DR+TNFR2+ Tregs will be measured in 150 kidney transplant recipients at scheduled intervals during the first 6 months post-transplant. Predictive accuracy of a model integrating ddcfDNA and HLA-DR+TNFR2+ Treg for acute rejection will be tested using ROC curve analysis and multivariate logistic regression. Predictive accuracy for 1-year graft function will be tested using multivariate linear regression. High predictive performance for acute rejection and graft function using a model integrating dd-cfDNA and HLA-DR+TNFR2+ Treg would help identify kidney transplant recipients at immunologic risk early on and allow personalization of immunosuppression accordingly.
Description
Background Despite advances in immunosuppression, 10-year graft survival after kidney transplantation has remained stagnant at around 50%. Timely diagnosis of acute rejection in kidney transplant recipients is essential for improving long-term graft survival. Clinical suspicion for acute rejection currently relies on monitoring elevation in serum creatinine and diagnostic confirmation with a kidney allograft biopsy. Serum creatinine elevation, however, is non-specific for acute rejection and is detected after significant immunological damage to the allograft already happens. Confirmation with…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * Adult kidney transplant candidates/recipients Exclusion Criteria: * Age less than 18 * Multi-organ transplants * Kidney transplant candidates/recipients with HIV * Kidney transplant candidates/recipients with HCV
Interventions
- Diagnostic TestDonor-derived cell-free DNA
As mentioned previously
Location
- Loma Linda University HealthLoma Linda, California