Research Group

  • Dr Heth Turnquist, Principal Investigator
  • Dr Benjamin Matta, Postdoctoral Scholar
  • Ms Lisa Mathews, Research Specialist
  • Ms Jane Luce, Research Coordinator
  • Dr Kaleabe Abebe, Statistician
  • Dr Jennifer Picarsic, Pediatric Pathologist
  • Dr Diana Metes, Collaborator
  • Dr Brian Feingold, Collaborator
  • Dr Eric Friedlander, Collaborator
  • Dr Steve Webber, Collaborator

Location

  • University of Pittsburg, Pittsburg, USA

Title

  • Prognostic Value and Function of IL-33/ST2 in Transplant Recipients with Infection

Solid organ recipient immunosuppressant therapy (IST) dulls all T cell responses and promotes viral complications, including post-transplant lymphoproliferative diseases (PTLD). PTLD is often driven by Epstein-Barr virus (EBV) infection and is a source of significant morbidity and mortality in pediatric transplant recipients. Recipients with PTLD or at high risk of developing PTLD require precise monitoring to balance IST at levels allowing immune EBV elimination, but not precipitating rejection. In pediatric heart transplant recipients, rejection diagnosis relies on endomyocardial biopsy (EMB). EMB is a costly and invasive procedure that is not overly precise or well suited for rapid or repeated testing of pediatric patients. We anticipate Aim 1 studies will establish serum soluble IL-33 receptor, originating from damaged or strained heart tissue, as a sensitive biomarker, which can distinguish rejection from other pathological conditions (i.e. viral infections or PTLD). Such a biomarker would improve pediatric heart transplant recipient care and outcomes by aiding non-invasive and dynamic IST management in patients with or at high risk of PTLD. Also, transplant recipients with the highest risk for PTLD can have CD8+ T cells that respond poorly to EBV and may have difficulty clearing infected cells. In Aim 2 we will establish distinct mechanisms by which IL-33 both supports expansion of regulatory T cell (Treg), important immune cells that suppress the responses of other T cells, as well as drives potent effector CD8+ (CTL) responses. This knowledge would immediately aid ongoing clinical assessments of ex vivo expanded recipient Tregs for tolerance induction/IST reduction, as well as generation of CTL for control of EBV disease or PTLD. It may also aid the development of novel therapies that promote IST-free allograft survival and/or support heart transplant recipient anti-viral T cell responses.

Final Report