TRANSPLANTED SMALL BOWEL AND EXPRESSION OF THE INSULIN-LIKE GROWTH FACTOR BINDING PROTEINS

Abstract

19 Insulin-like growth factor binding proteins (IGFBPs) act to modulate the growth and differentiation of the gastrointestinal mucosa by regulating cellular responses to the insulin-like growth factors (IGFs). The transplanted small bowel must maintain the normal growth factor interrelationships and signaling pathways despite the potential of host rejection. Ostomy effluents of patients after small bowel or liver/small bowel transplantation were assayed for IGFBPs to investigate the effect of rejection on the IGF-IGFBP axis. A total of 17 patients were studied over an eighteen-month period. The total protein present in the fluid was assayed by the bicinchoninic acid method. There were no statistically significant differences in protein content of the ostomy fluids in the presence or absence of rejection. The ostomy effluent was then subjected to ligand blotting to assess for the presence of IGFBPs. The transplanted small bowel produced no measurable IGFBPs in the ostomy effluent under normal circumstances. However, when rejection was taking place the ostomy effluent was found to have measurable IGFBP levels in 6 of 12 episodes, the 6 episodes occurring in 6 different patients, predominantly IGFBP-3 was observed, but IGFBPs 2 and 4 were present. Two additional patients had IGFBPs present when the histology did not demonstrate rejection. These two patients appeared to have rejection clinically and in both instances, a re-biopsy after 48 h demonstrated rejection. The IGFBPs present did not exhibit a serum-like pattern indicating the secretion of IGFBPs into the effluent was not the result of loss of mucosal barrier integrity. Our results suggest that the gastrointestinal IGF axis is altered during transplanted small bowel rejection, with increased secretion of IGFBPs that may contribute to mucosal loss.