Research Group

  • Prof. Karl Womer, Principal Investigator
  • Dr Yanfei Huang, Research Associate
  • Ms Cassie Zhang, Lab Technician

Location

  • Johns Hopkins University, Baltimore, USA

Title

  • The Role of Dendritic Cell Dysfunction in BK Nephropathy

BK virus nephropathy is a significant cause of kidney transplant graft loss that involves immunosuppression-induced reactivation of the virus in the transplanted kidney following transplantation. As no current antiviral agents are effective, the only proven therapy is to monitor frequently for the virus by polymerase chain reaction (PCR) and reduce immunosuppression until viral replication has ceased. This approach is time consuming and not always cost effective, since only a certain percentage of kidney transplants will develop the condition. Furthermore, such an approach can precipitate acute rejection in high-risk patients.

Our preliminary data have demonstrated a numerical deficiency of pre-transplant peripheral blood dendritic cells (PBDCs) in patients who subsequently developed BK viremia post-transplantation. As DCs are immune cells that are important for containment of viral infections, the deficiency may have predisposed the patients to viral reactivation. Furthermore, it appears that the pre-transplantation levels are reasonably predictive of which patients will develop reactivation post-transplantation, which could allow more focused, and therefore less costly, screening as well as more refined management of immunosuppression. However, these findings need to be validated in a larger patient set.

The primary aim of the proposal is to determine the ability of prospectively measured pre-transplantation PBDCs to predict BK virus reactivation during the first year post-transplantation. Secondary analyses, such as time to development of reactivation and response to reduction of immunosuppression, will also be performed. In the second and third aims, we will evaluate potential functional deficiencies associated with the noted numerical deficiency, in an effort to elucidate the immunologic mechanisms responsible for BK virus reactivation, as well as to identify potential targets for immunotherapy designed to augment the antiviral response. Thus, the findings may be readily translated into clinical practice and, in addition, serve as the basis for subsequent interventional trials.

Progress Report
Final Report