Evolution of the immunosuppressive strategies for the intestinal and multivisceral recipients with special reference to allograft immunity and achievement of partial tolerance

Abstract

Summary Introduction of new innovative immunosuppressive strategies has been the milestone of the recent evolution of intestinal and multivisceral transplantation. With new insights into the mechanisms of organ engraftment and acquired tolerance, the Pittsburgh tolerogenic protocol was recently introduced and consisted of two main therapeutic principles: recipient pretreatment with lymphoid ablating antibodies and minimal post‐transplant immunosuppression with tacrolimus monotherapy. The reported herein improved survival and the striking ability to wean immunosuppression among the intestinal and multivisceral recipients pretreated with a single‐dose of Thymoglobulin (rATG) or Campath‐1H (alemtuzumab) supports our working hypothesis with successful induction of variable tolerance. It is important, however, that careful monitoring of subtle histologic changes in serial endoscopic‐guided mucosal biopsies be carried out for early diagnosis of allograft immune activation with prompt restoration of the baseline immunosuppressive therapy. Future scientific discoveries with better understanding of the mechanisms of immune tolerance and clinical introduction of reliable assays will increase the chance and safety of achieving complete tolerance among the intestinal and other solid organ recipients. This review will focus on the historic evolution of the immunosuppressive and other management strategies utilized for the intestinal and multivisceral recipients at the University of Pittsburgh with special reference to allograft immunity and the successful achievement of partial tolerance.

En Bloc Multivisceral and Kidney Transplantation in an HIV Patient: First Case Report

“…We currently believe that a suppressed state of HIV viral replication is an essential prerequisite for VT. With the associated massive lymphoid tissue, it is conceivable that VT, contrary to solid organs, may carry a higher risk of HIV reactivation due to the high lymphophylic affinity of the virus (11)(12)(13)(14). This assumption may be supported by the documented phenomenon of visceral allograft repopulation with recipient lymphocytes (22).…”

“…Technical difficulties stemmed from the complex abdominal pathology encountered in end-stage liver failure patients with PMVT and multiple prior abdominal operations. Some of the known immunologic challenges are the robust gut alloimmune response and the immune dysregulations associated with HIV infection (2,11,13,14). Similar unfavorable outcome was observed in an unpublished case that was performed at the University of Miami.…”

“…Pretreatment of the recipient with an antilymphocyte agent was deferred because of the potential risk of previously observed and published life-threatening intraoperative coagulopathy with fibrinolysis, particularly in patients with extensive PMVT (11). In these complex patients, extensive intra-abdominal dissection is challenging in the milieu of severe portal hypertension and diffuse portomesenteric collaterals.…”

“…Immunosuppression was tacrolimus-steroid-based with no induction therapy or recipient pretreatment (3,11,18). Pretreatment of the recipient with an antilymphocyte agent was deferred because of the potential risk of previously observed and published life-threatening intraoperative coagulopathy with fibrinolysis, particularly in patients with extensive PMVT (11).…”

“…With gut failure being the main indication, the impaired absorptive capacity with short-gut syndrome (SGS) may limit the choice and effectiveness of HAART to achieve undetectable viral load as a prerequisite for transplantation. After transplantation, the inherent allograft immunogenicity may provoke destructive alloimmune response with the need for counterintuitive heavy immunosuppression (11,12). In addition, allograft dysfunction may compromise efficacy and sustainability of HAART.…”