Renal allograft surveillance with allospecific T-cytotoxic memory cells

Abstract

Background Allo-antigen-specific T-cytotoxic memory cells (TcM) which express CD40 ligand (CD154) in overnight lymphocyte co-culture are strongly associated with acute cellular rejection (ACR) seen in “for cause” biopsies for renal allograft dysfunction. Specifically, when the likelihood of rejection is increased, donor-specific allospecific TcM exceed those induced by HLA-non-identical third-party cell by 1.15-fold or greater. Methods The performance of allospecific TcM was evaluated retrospectively in primary renal transplant recipients (RTR) at routine clinical visits, cross-sectionally at presentation for biopsies, and serially. Performance metrics were sensitivity, specificity, positive and negative predictive values (PPV and NPV). Results Twenty-two primary RTR, median age 45 years (range 19–72) were tested with allospecific CD154 + TcM. Samples were obtained at the mean ± SD time interval of 806 ± 239 days after kidney transplantation. Six of 22 patients experienced biopsy proven T- Cell Mediated Rejection (TCMR). A seventh showed antibody mediated rejection (ABMR). Of these seven patients six demonstrated increased likelihood of rejection with allospecific TcM (sensitivity 83%). Ten of these 15 patients with no rejection had a negative test (specificity 67%). False positive tests were seen in five patients. Six out of 11 patients with positive tests had ACR/ABMR with a PPV of 54%, while 10 out of 11 patients with negative tests were non-rejecters with a NPV of 91%. Conclusion Allospecific T-cytotoxic memory cells distinguished primary RTR with quiescent allografts from those with dysfunction. With serial surveillance measures, this test system may facilitate decisions to manage immunosuppression in RTR.

Biomarkers for Kidney-Transplant Rejection: A Short Review Study

“…However, the results were deemed weak due to a low sample size and a wide confidence interval. Rohan et al [ 16 ] conducted a study to assess the efficacy of allospecific CD154+ TcM in 22 individuals who received kidney transplants. Out of the 22 patients, 6 experienced TCMR and 7 showed ABMR.…”

“…The mentioned studies investigated different types of rejection in kidney-transplant recipients. A common finding among these studies was the importance of T-cell mediated rejection (TCMR) and antibody-mediated rejection (ABMR) in acute rejection [ 16 , 17 , 19 , 20 , 21 , 26 ]. Several studies identified the biomarker CD4+ CD25+/CD39+ expression to predict acute cellular rejection (ACR) as well [ 23 , 24 , 27 ].…”

“…The mentioned studies investigated different types of rejection in kidney-transplant recipients. A common finding among these studies was the importance of T-cell mediated rejection (TCMR) and antibody-mediated rejection (ABMR) in acute rejection [16,17,[19][20][21]26].…”

Tackling Chronic Kidney Transplant Rejection: Challenges and Promises

“…Resent studies showed that monitoring alloreactive memory IFN-γ-producing T cells could assess subclinical TCMR and predict de novo DSA ( 82 ), while ratio of T follicular helper cells and T follicular regulatory cells (Tfc/Tfr) was an independent risk factor for CAD ( 83 ). However, multicenter validation of its diagnostic/prognostic biomarker utility in CKTR remains to be determined ( 108 ). Both macrophages and NK cells are implicated in chronic rejection ( 21 , 109 – 111 ).…”