Novel Autoimmunte Pathways Leading to Chronic Lung Allograft Rejection

Project: Research project

Project Details

Description

Primary graft dysfunction (PGD) affects over 50% of lung transplant recipients within 24 hours. Additionally, chronic rejection occurs (CR) with up to 60% of recipients in 5 years. PGD and CR remains the major cause of short- and long-term mortality as well as graft loss, respectively. Nevertheless, their pathogenesis remains undefined. Our recent clinical data indicates that autoantibodies against lungtissue restricted self-antigens mediate PGD and remain one of the strongest risk factors for chronic rejection. We hypothesize that activation of B cells and production of autoantibodies, both pretransplant and de novo, play an important role in mediating lung allograft rejection. Using a murine model of lung transplantation, we will determine the role of autoantibodies in the development of acute and chronic graft loss as well as abrogation of immunosuppression-induced tolerance. Since, CD4+CD25+Foxp3+ regulatory T cells (Tregs) suppress autoreactive B cells, we will further determine whether loss of Tregs following transplantation leads to the development of autoimmunity. Completion of these studies will demonstrate a pivotal role of autoantibodies in the lung allograft rejection. Since the current immunosuppression and organ cross-matching techniques do not consider autoimmunity, our studies will propose a paradigm change in the management of patients undergoing lung transplantation.
StatusFinished
Effective start/end date1/1/1612/31/16

Funding

  • Northwestern Memorial Hospital (Agreement 2/3/16)

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