Research Group
- Dr Banu Sis, Principal Investigator
- Dr Philip F. Halloran, Collaborator
- Dr Thomas F. Mueller, Collaborator
- Ms Guttikonda Sujatha, Technician
Location
- University of Alberta, Alberta, Canada
Title
- The Transcriptome of Antibody-mediated Rejection in Human Renal Allografts
Among the most challenging subjects in solid organ transplantation is antibody-mediated rejection (ABMR). ABMR in human organ allografts is associated with poor graft survival and is a major cause of allograft loss. However, the pathogenesis of ABMR, how the disease arises and causes tissue injury, remains unknown. Furthermore, the distinction between T cellmediated rejection (TCMR) and ABMR is crucial since these two forms of rejection require different treatments and ABMR does not respond to conventional anti-T cell therapy. The effects of alloantibodies and ABMR on the transcriptome are currently unknown. This project will elucidate gene expression profiles of ABMR in human kidney allograft biopsies using Affymetrix microarrays. We have preliminary data that increased expression of endothelial cell-associated genes and NK cell-associated genes distinguishes ABMR from T cell-mediated rejection. We wish to define transcriptome changes of ABMR in human renal allografts. The transcriptomics studies provide a unique opportunity to uncover mechanisms underlying ABMR and tissue injury which may progress to graft loss. These changes may correlate to more subtle changes that may become apparent earlier than overt graft damage and loss. Understanding of the pathogenesis of ABMR with identification of the mechanisms and effector molecules would reveal novel targets for pharmacological intervention, revision of new end-points for trials, as well as development of new monitoring systems that could be applied to blood, urine and tissue specimens.
Final Report
