May 4, 2015
J. Friedewald, S. Kurian, T. Gelbart, D. Salomon, M. Abecassis
We have discovered and clinically validated a gene expression profile in the peripheral blood of patients with subAR. This gene expression profile (subAR) differs from a previously validated peripheral blood signature for patients with clinical acute cellular rejection found on a “for cause” biopsy (cAR). We also developed a molecular scoring system to help determine clinical phenotypes based on peripheral blood gene expression profiles. Our study expands the repertoire of clinical phenotypes that can be identified through noninvasive genomic monitoring, and demonstrates the potential of integrating predictive molecular biomarkers into clinical practice to serially monitor and improve long-term outcomes for kidney transplant patients.
May 3, 2015
B. Modena, S. Kurian, J. Friedewald, F. Harrison, T. Gelbart, S. Head, M. Abecassis, D. Salomon
We sought to show by differential gene expression that the arc of AR immune responses, injury and metabolic mechanisms could be identified in Interstitial fibrosis and tubular atrophy (IFTA) phenotypes. We then looked at correlation of these findings with long-term graft function and survival.
May 3, 2015
S. Kurian, J. Friedewald, F. Harrison, T. Gelbart, S. Head, P. Ordoukhanian, M. Abecassis, D. Salomon
We compare gene expression signatures obtained from peripheral blood and biopsies using both global profiling platforms to evaluate their diagnostic capabilities to differentiate subclinical Acute Rejection (subAR) from clinical Acute rejection (cAR) and Transplant eXcellent subjects (TX). A second objective was to provide a validation of our array-based gene expression diagnostics using an orthogonal RNA expression technology.
July 31, 2014
J. Levitsky, D. Salomon, S. Kurian, J. Friedewald, S. Rao, A. Demetris, S. Rindt, J. Charette,
In both the peripheral blood and graft tissue from liver transplant recipients, we have identified gene expression classifier sets that can distinguish between AR, HCV and HCV+AR with AUCs between 0.79-0.83 (blood) and 0.69-0.83 (biopsies). We have also discovered profiles in whole blood that can distinguish between AR, ADNRR and normal TX with AUCs ranging from 0.87-0.92. These signatures have the potential to enhance: decision-making in the need to perform liver biopsy, the specificity of diagnosis, particularly in managing patients with contrasting etiologies (e.g., AR vs. HCV-R vs. ADNRR), the understanding of mechanisms of graft injury in LT recipients, and the ability to minimize immunosuppression or need to augment. Prospective multicenter studies, including our NIAID funded CTOT-14 are underway to validate these diagnostic signatures, test their predictive value before graft injury occurs, and determine how they respond to therapy.
July 30, 2014
J. Friedewald, S. Kurian, J. Levitsky, S. Brietigam, J. Charette, M. Abecassis, D. Salomon
We have discovered a gene expression profile in the peripheral blood of patients with acute cellular rejection on a surveillance protocol biopsy (SCAR) that is different from that of patients with normal protocol surveillance biopsies (TX – normal creatinine). This gene expression profile (SCAR) differs from a previously validated peripheral blood profile/signature for patients with clinical acute cellular rejection (AR - elevated creatinine) found on a “for cause” biopsy. Peripheral blood gene expression profiling may prove to be a useful, minimally invasive method for monitoring kidney transplant recipients. We are currently validating this SCAR signature in the multi-center NIH-funded (CTOT-08) study.
July 29, 2014
S. Kurian, T. Gelbart, K. Reddy, M. Smith, D. Salomon, R. Heilman
In this study, we wanted to determine if we could use kidneys from donors with severe acute kidney injury (AKI) without compromising post-transplant outcomes. We reasoned that gene expression profiles of patient biopsies, 1 and 4 months post- transplant, would reveal the resolution of donor AKI-induced injury as well as signals of early graft dysfunction if present. In conclusion, 1-month biopsies of recipients of AKI kidneys show many differentially expressed genes associated with cell death/stress, inflammation and disrupted metabolic processes typical of kidney injury. By four months these injury/inflammation signals have resolved. These results support the routine use of properly selected AKI donors.
July 27, 2014
S. Kurian*, B. Modena, J. Friedewald, S. Brietigam, J. Charette, C. Ventura, E. David-Neto, M. Abecassis, D. Salomon
We report on the global gene expression profiles from ~400 kidney transplant patients encompassing four major phenotypes, well-functioning kidney grafts (TX), Acute Rejection (AR), Chronic Rejection(CR) and grafts that have acute dysfunction but due to causes other than rejection (ADNR). This study used the current “gold standard”, light histology, to test correlations of our molecular phenotypes to graft survival and function. We also mapped gene expression to reveal the biology of AR and CR.
July 27, 2014
C. Ventura, S. Kurian*, T.Gelbart, D. David, F. Agena, M. Abecassis, J. Friedewald, E. David-Neto, D. Salomon.
In this study, we determined both the peripheral blood and biopsy gene expression profiles of Brazilian transplants with Acute Rejection (AR), Acute Dysfunction/No Rejection (ADNR), Chronic Allograft Nephropathy (CAN/IFTA), recurrent and de novo Transplant Glomerular Disease (TGDz) and Transplant Excellent (TX). This is the first discovery study of molecular phenotypes in Brazilian transplant patients.