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Intragraft Immunological Response Characterized by GeneChip Analysis From the First Living-Related Small Bowel Transplant in New England
Sean P Bradley1, Mohan P Pahari1, Cristiana Rastellini1, Marc E Uknis2, Luca Cicalese1
1University of Massachusetts Medical School, Worcester, MA;2St Barnabas Medical Center, Livingston, NJ
Objective: For the intestinal graft to function successfully, the donor mucosal immune system must be replaced by that of the host. The need to understand early immune responses of the donor graft is of vital importance for graft survival. The AIM of this study was to characterize the genetic pathways altered in the intestinal graft which may have a role as biomarkers for rejection, inflammation, and graft viability.
Design/Setting: Serial biopsy gene analysis. The first LR-SBTx case conducted in New England took place at the UMass/Memorial HealthCare Center. Mucosal biopsies were obtained from the donor and recipient intestine at (day 0) and intragraft biopsies taken on days 7, 14, 21, and 42 post-transplant. Total RNA was isolated followed by microarray analysis using the Affymetrix GeneChips.
Main Outcome Measure: Increased intragraft gene expression levels in response to transplant were used to develop our hypothesis.
Results: The expression profiles revealed 176 genes decreased their expression 3 fold (P<0.05) by 7 days post-SBTx which includes many inflammatory response genes such as IL-6 and IL-8. Another profile showed two major pathways, cell proliferation and an interferon induction pathway, activated after day 21.
Conclusions: The expression profiles have identified a down regulation of inflammatory genes by post-op day 7 likely due to the immunosuppression regiment. Increases in gene expression of many genes involved in cell proliferation and an interferon inducible response does correlate with T cell infiltration and was confirmed with zoom endoscopy and biopsy histology diagnosing mild cellular rejection during post-op week 3.
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