Background

IL-33 is a member of the IL-1 cytokine family with functions ascribed to its actions on immune cells expressing the IL-33 receptor, ST2. Following heart transplantation, soluble ST2 (sST2) is increased in the allograft and the circulation during acute rejection (AR). We hypothesized that that high serum and tissue levels of IL-33 or sST2 would correlate with AR following small bowel transplantation (SBTx).

Methods

The patient samples were obtained from an established, institutional review board-approved tissue collection bank. We used ELISA to evaluate serum levels of IL-33 and its soluble receptor sST2 in patients with and without AR. We also evaluated the tissue expression of IL-33 and its membrane-bound receptor ST2 in intestinal allograft biopsies from patients with and without AR by quantitative real-time PCR.

Results

Serum levels of sST2 were significantly increased at the time of histologic mild, moderate or severe AR (21 incidences) compared to the same patients without AR (17 incidences; p = 0.009; see figure). Increases in sST2 seemed specific to AR and differentiated it from non-specific enteritis. Levels of IL-33 were also increased during AR when compared to samples without AR (p = 0.04). A 1.6-fold increase in IL-33 mRNA expression was noted in 8 AR samples when compared to 13 samples without AR (p = 0.7). Mean ST2 expression had a significant 4-fold increase in AR samples (p = 0.02).

Conclusions

Significant morbidity, mortality, high rates of AR, and graft loss currently plague SBTx. We provide exciting new evidence that IL-33 and sST2 can identify AR in SBTx. That sST2 could differentiate AR from enteritis supports expanded examinations to assess if serum sST2 measures can improve outcomes in these patients.

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