Cal Matsumoto, Stuart Kaufman, Raffaele Girlanda, Eddie Island, Cheryl Little, Kirti Shetty, Erin Fennelly, Thomas Fishbein

Transplant Institute, Georgetown University Hospital, Washington, DC, United States

Human CMV infection, a member of the herpes virus family, has routinely been established as a risk factor for increased morbidity and mortality in intestinal transplantation (iTx). Reactivation of latent CMV has been postulated to be a result of an increased proinflammatory state of cytokines and chemokines. In inflammatory bowel disease, a relationship has been established between colitis exacerbations and the reactivation of latent CMV. We have previously demonstrated the association between NOD2 polymorphisms and the abnormal epithelial immune function in iTx recipients. The purpose of this study is to evaluate the relationship between NOD2 mutant iTx recipients and the incidence of CMV infection.

35/134 (25.9%) iTx recipients were identified as having at least one NOD2 polymorphism. 8/35 NOD2 Mutants were CMV serotype matching neg/neg and were excluded from CMV reactivation analysis. Likewise, 50/99 NOD2 Wildtype were neg/neg. 18/35 NOD2 Mutants and 38/99 NOD2 Wildtype had a liver-inclusive intestinal graft. Overall Freedom from CMV was not different between the 2 groups with NOD2 Mutant (69.6%) vs. NOD2 Wildtype (75.3%) p=ns. Recurrent CMV, however, was more prevalent in the NOD2 Mutant group 7/35 vs 4/99 (p=0.019). In evaluation of CMV reactivation (excluding CMV neg/neg matching), no significant difference was noted in overall Freedom from CMV between the 2 groups however, NOD2 mutants in this group had a significantly higher incidence of CMV recurrence than the NOD2 Wildtype, 7/27 vs. 4/47 respectively, (p = 0.04).

NOD2 Mutation in iTx recipients appears to play a role in the incidence of CMV recurrence after initial CMV infection. Perhaps an chronically altered and dysregulated inflammatory state in the NOD2 Mutant iTx recipient plays an important role in the increased recurrence of CMV infection in this population. A role for a more aggressive CMV prophylaxis in this subset of iTx recipients appears warranted.