Research Group
- Dr Thomas Fishbein, Principal Investigator
- Dr Michael Zasloff, Co-Investigator
- Mr Denver Lough, Res. Associate
- Mr Joseph Abdo, Res. Associate
Location
- Georgetown University, Washington DC, USA
Title
- Innate Immunity of the Transplanted Human-small Intestine
Small intestinal transplantation is performed in individuals who have lost functional bowel and can no longer be fed intravenously. Although remarkable progress has been made in this procedure over the past 15 years, with over 600 transplants performed worldwide, organ rejection is still a significant problem, with graft failure occurring within 3-4 years in about 30% of patients. We have reported recently that a high percentage of transplant recipients carried specific genetic mutations in the NOD2 gene, which codes for a microbe sensor that plays an important role in the immune health of the small intestine. When an otherwise “healthy” donor intestine was transplanted into an individual who carried a NOD2 mutation, the risk of rejection was almost 100-fold greater than observed when the bowel was transplanted into an individual with “normal” NOD2 genes. Within weeks of transplantation into a NOD2-mutant recipient, a “normal” donor small intestine lost its capacity to sustain the production of key antimicrobial substances required to protect the bowel wall from assault by its own normal resident bacteria. In this proposal we design experiments to better understand how the mutations in the recipient’s NOD2 gene leads to a failure of the allograft’s microbial defenses.
Progress Report
