HISTOPAHTOLOGIC CHARACTERISTICS OF HUMAN INTESTINE ALLOGRAFT ACUTE REJECTION IN PATIENTS WITH TOLERIGENIC IMMUNOSUPPRESSION

Abstract

O59* Aims: We report herein the histopathologic characteristics of human intestine allograft acute rejection in a consecutive series of 48 patients receiving small bowel transplantations and treated with a tolerogenic immunosuppressive protocol between July 4, 2001 to January 31,2004. Two therapeutic principles were observed in this protocol: recipient pretreatment and minimum use of post-transplant immunosuppression. Methods: Recipient pretreatment was with an intravenous infusion of 5–10 mg/kg Thymoglobulin or 30–60mg of Campath 1H over several hours prior to revascularization. Postoperative treatment was limited to tacrolimus (target 12-hour trough level 10–15 ng/ml) unless additional drugs were needed to treat breakthrough rejection. Results: A total of 3497 biopsies of the allograft jejunum and/or ileum were obtained. A recently validated histological grading schema (Transplantation 2003, 75:1241–1248) was perspectively utilized to grade acute rejection. 68 acute rejection episodes were diagnosed prior and during the weaning process (36 mild, 11 moderate and 21 severe). The mean acute rejection episode is 2.2±1.6 per patient, which is comparable to that in patients with conventional immunosuppression. Several unique histopathologic features of allograft acute rejection were observed in patients with tolerogenic immunosuppression. First, scattered lamina propria neutrophilic inflammation often precedes the onset of acute rejection. Second, acute rejection is often associated with more prominent eosinophils in lamina propria or eosinophilic cryptitis. Third, certain acute rejection episodes are characterized by marked lamina propria mixed inflammation and crypt loss without significant crypt apoptosis. Finally, the mucosal damage associated with moderate or severe acute rejection can completely recover after additional immunosuppressive treatment. Conclusions: This study reveals that tolerogenic immunosuppressive protocol can be safely applied to small intestine transplant patients. Recognition of unique histopathologic features of intestine allograft rejection will enable early diagnosis and prompt treatment and safe spaced weaning of the immunosuppressive drugs.