title: Incidence of graft rejection in small bowel transplanted pigs after immunosuppression withdrawal.
abstract: As intestinal grafts require heavy immunosuppression, there are no reports of immunosuppression withdrawal after clinical small bowel transplantation. In this large-animal study, we investigated the occurrence of graft rejection in intestinal-transplanted pigs after withdrawal. Large-White unrelated piglets were transplanted and divided in three groups: group 1 (n = 5), intestinal transplantation (ITx) with no immunosuppression; group 2 (n = 7), Itx and 60 days of treatment with tacrolimus and mycophenolate mofetil; group 3 (n = 5), Itx and donor bone marrow infusion (DBMi) and 60 days of treatment with tacrolimus and mycophenolate mofetil. Follow-up time after withdrawal was 120 days. Group 1 pigs died of graft acute cellular rejection (ACR) after a median of 11 days. In group 2, two pigs died of ACR-related infection and another two of ACR within 90 days. The remaining three animals (43%) were sacrificed at day 180, and their grafts showed no signs of ACR. In group 3, two pigs died of ACR-related infection and one of graft versus host disease within 80 days; at day 180 the two surviving animals showed signs of chronic rejection in the allograft. This study demonstrates that total withdrawal after ITx is followed by sudden and lethal ACR (or ACR-related infection) in more than 50% of the recipients. When a tolerance-inducing strategy as DBMi is applied, lethal graft versus host disease may also occur. In group 3, the intestinal allograft, to which the recipients were partially tolerant, developed chronic rejection that was probably associated with a decline with time of donor-leukocytes chimerism, as recently demonstrated in rats.
authors.affiliation: Department of Surgery, University of Pavia School of Medicine and I.R.C.C.S. Policlinico San Matteo Hospital, Piazzale Golgi 2, 27100 Pavia, Italy.
authors.forename: J
authors.initials: J
authors.lastname: Viganó
authors.forename: F
authors.initials: F
authors.lastname: Abbiati
authors.forename: M
authors.initials: M
authors.lastname: Alessiani
authors.forename: M
authors.initials: M
authors.lastname: Bonfichi
authors.forename: S
authors.initials: S
authors.lastname: Zonta
authors.forename: M
authors.initials: M
authors.lastname: Bardone
authors.forename: E
authors.initials: E
authors.lastname: Zitelli
authors.forename: L
authors.initials: L
authors.lastname: Cobianchi
authors.forename: M
authors.initials: M
authors.lastname: Doni
authors.forename: F
authors.initials: F
authors.lastname: Lovisetto
authors.forename: T
authors.initials: T
authors.lastname: Dominioni
authors.forename: M
authors.initials: M
authors.lastname: De Martino
authors.forename: B
authors.initials: B
authors.lastname: Lusona
authors.forename: E
authors.initials: E
authors.lastname: Arbustini
authors.forename: P
authors.initials: P
authors.lastname: Dionigi
mesh_terms: D000208:Acute Disease; D000818:Animals; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D006084:Graft Rejection / Q000453:epidemiology*; D007165:Immunosuppression Therapy / Q000379:methods*; D015994:Incidence; D007421:Intestine, Small / Q000637:transplantation*; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use; D013375:Substance Withdrawal Syndrome / Q000453:epidemiology*; D013552:Swine; D016559:Tacrolimus / Q000008:administration & dosage / Q000627:therapeutic use
chemical_list: D009173:Mycophenolic Acid; D016559:Tacrolimus