Research Group
- Dr Behzad Najafian, Principal Investigator
Location
- University of Washington Medical Center, Seattle, USA
Title
- Discovery of a Blood Test to Diagnose Kidney Transplant Rejection
Over 65,000 kidney transplantations are performed per year around the world. While the advent of modern immunosuppressive drugs has improved short-term graft survival, improving long-term survival of allografts is still a challenge. Antibody-mediated rejection (ABMR) is a major cause of chronic graft loss. Currently, diagnosis of this type of rejection requires kidney biopsy and there is no non-invasive test available. We aim to develop a non-invasive assay for ABMR to facilitate early diagnosis and treatment of this condition to improve graft survival. Injured cells release small membrane bound vesicles called "microparticles". The allograft endothelium is the major target of ABMR. Therefore, we anticipate that ABMR is associated with release of microparticles from graft endothelial cells into the blood. Hypothetically these endothelial microparticles can thus be used as a biomarker of ABMR. The challenge is how to recognize those microparticles that are released from the graft endothelium, and not other organs, due to ABMR, and not other types of injury. During ABMR, donor antibodies bind to the mismatched HLA molecules of allograft endothelium, which subsequently leads to classical complement pathway activation. Therefore, we hypothesize that endothelial microparticles generated due to ABMR carry footprints of classical complement pathway activation. We will check for these footprints on blood endothelial microparticles of transplant patients with and without ABMR to see if these microparticles are increased in ABMR, if such increase is specific for ABMR, and finally if the blood concentration of endothelial microparticles with such footprints correlates with severity of rejection. Accomplishment of these goals may lead to discovery of a non-invasive quantitative assay for ABMR.
Progress Report
