Derivation and Validation of a Cytokine-Based Assay to Screen for Acute Rejection in Renal Transplant Recipients

Abstract

SummaryBackground and objectives Acute rejection remains a problem in renal transplantation. This study sought to determine the utility of a noninvasive cytokine assay in screening of acute rejection.Design, setting, participants, & measurements In this observational cross-sectional study, 64 patients from two centers were recruited upon admission for allograft biopsy to investigate acute graft dysfunction. Blood was collected before biopsy and assayed for a panel of 21 cytokines secreted by PBMCs. Patients were classified as acute rejectors or nonrejectors according to a classification rule derived from an initial set of 32 patients (training cohort) and subsequently validated in the remaining patients (validation cohort).Results Although six cytokines (IL-1b, IL-6, TNF-a, IL-4, GM-CSF, and monocyte chemoattractant protein-1) distinguished acute rejectors in the training cohort, logistic regression modeling identified a single cytokine, IL-6, as the best predictor. In the validation cohort, IL-6 was consistently the most accurate cytokine (area under the receiver-operating characteristic curve, 0.85; P=0.006), whereas the application of a prespecified cutoff level, as determined from the training cohort, resulted in a sensitivity and specificity of 92% and 63%, respectively. Secondary analyses revealed a strong association between IL-6 levels and acute rejection after multivariate adjustment for clinical characteristics (P,0.001).Conclusions In this pilot study, the measurement of a single cytokine can exclude acute rejection with a sensitivity of 92% in renal transplant recipients presenting with acute graft dysfunction. Prospective studies are needed to determine the utility of this simple assay, particularly for low-risk or remote patients.

Rapamycin Combined with Immature Dendritic Cells Attenuates Obliterative Bronchiolitis in Trachea Allograft Rats by Regulating the Balance of Regulatory and Effector T Cells

“…IL-17, IFN-γ and TNF-α) and low immunosuppressive cytokines (e.g. IL-10 and TGF-β1) [28,29,30]. In this study, Rapa-imDC treatment downregulated the amounts of proinflammatory factors in grafts, including IL-6, TNF-α, IFN-γ and IL-17.…”

Urinary Cell mRNA Profiles and Differential Diagnosis of Acute Kidney Graft Dysfunction

“…Moreover, IL-6 levels did not differentiate ACR from AMR. 17 In a study of 21 ACR and 8 AMR patients, urinary protein levels of endothelial protein c receptor differentiated ACR from AMR with an AUC of 0.875. This study, however, did not include patients with ATI.…”

Flow Cytometry and Solid Organ Transplantation: A Perfect Match

“…The multiplex ability of the bead array is attractive to efficiently measure multiple targets simultaneously. These assays have shown promise in detection of adverse post-transplant responses with increased serum IL-6 and FGL2 identified as potentially predictive of acute rejection in in vitro studies (De Serres et al, 2012; Zhao et al, 2013). This approach however has the same drawback as the ELISPOT analysis in that it cannot be used to identify the cytokine-producing cells.…”