After kidney transplantation, patients would normally be on immunosuppressive drugs for life (usually a triple drug regimen, based on steroids).Dr. Minnie Sarwal (Stanford University) and her colleagues have discovered a non-invasive, peripheral blood biomarker panel of ~50 genes, which can be used to serially follow and rapidly determine which patients develop spontaneous tolerance to their transplanted organs. These patients may not require chronic immunosuppression treatment following kidney transplantation, decreasing their risk of infection, malignancy and drug nephrotoxicity, which accompanies chronic immunosuppression. As a rare occurrence, these patients have spontaneously accepted their transplanted organ as self, when tested "accidentally" by a process of medication self-withdrawal by the patient or occasionally, deliberate withdrawal by the physician. In the face of an otherwise intact immunity, it is evident that some patients’ immune systems can evolve post-transplantation, to adapt and spontaneously accept a transplanted organ from a third party, without any evidence of organ injury. Dr. Sarwal has studied peripheral blood samples from these patients by global gene expression analysis to develop biomarker panel of genes in peripheral blood, that can diagnose tolerance in transplanted patients, with very high prediction scores. This biomarker gene-set has been cross validated across an independent test-group of tolerant patients, where the gene-set can predict the development of a tolerant phenotype with 100% prediction. This same gene-set can now be used for screening peripheral blood samples of patients on chronic immunosuppression, to identify those with tolerant class prediction scores of >90%, suggesting that these patients could then be targeted for immunosuppression individualization and minimization. This customized gene set has been validated by PCR-based analysis on RNA extracted from total blood samples of graft-tolerant, stable (graft-tolerant status unknown) and graft-intolerant adult patients after kidney transplantation. Thus, patients who develop tolerance after transplantation can now be identified by a high-throughput, low cost, PCR based assay, with the potential to withdraw these patients safely from all their immunosuppressive medication, without risk of organ rejection, and with the added benefit of removing all drug related morbidity (eg. increased risk of developing neoplastic disease conditions, infections and chronic organ injury due to drug related toxicity). [ - ]

After kidney transplantation, patients would normally be on immunosuppressive drugs for life... [ + ]