Immunologic Challenges in Small Bowel Transplantation

Since the introduction of tacrolimus, small-bowel and multivisceral transplantion has increased to 100200/year in the United States. The intestine carries more passenger lymphocytes than other organs, and bidirectional trafficking of lymphocytes and other immunocytes begins as soon as the vascular clamp is released. Because of ischemia-reperfusion injury and exposure to ligands for Toll-like receptors from the lumen, the innate immune system of the graft is activated, causing inflammation which must be brought under control by regulatory cells. Inclusion of the liver in the allograft favors graft acceptance, but the mechanism of this effect has not been determined. Anti-HLA and other anti-donor antibodies clearly play a major role in determining the long-term fate of the graft, as reflected in 5-year graft survival. Development of new (de novo) HLA antibodies and/or increases in their titers or functionespecially the ability to bind C1q and activate complement increase the risk of graft loss. Monitoring antidonor antibody production and the use of new therapies including complement inhibitors will contribute to increasing success of SBT.