Histopathologic Characteristics of Human Intestine Allograft Acute Rejection in Patients Pretreated with Thymoglobulin or Alemtuzumab

Abstract

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 preconditioning protocol between July 4, 2001 and January 31, 2004. Recipient pretreatment was with an i.v. infusion of 5-10 mg/kg thymoglobulin or 30-60 mg of alemtuzumab (Campath 1H) over several hours prior to revascularization. Postoperative treatment was limited to tacrolimus (target 12-h trough level 10-15 ng/mL) unless additional drugs were needed to treat breakthrough rejection. A total of 3,497 biopsies of the allograft jejunum and/or ileum were obtained. A recently validated histological grading schema was prospectively utilized to grade acute rejection. A total of 116 acute rejection episodes were diagnosed (48 indeterminate, 36 mild, 11 moderate, and 21 severe). Several unique histopathologic features of allograft acute rejection were observed in the pretreated patients. 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 absence of crypts with intact surface villous epithelium. Finally, the mucosal damage associated with moderate or severe acute rejection can completely recover after additional immunosuppressive treatment. This study describes several characteristic histopathologic features of allograft small bowel acute rejection associated with thymoglobulin or alemtuzumab preconditioning. Recognition of these unique histopathologic features will enable accurate diagnosis and ensure successful weaning of immunosuppressive drugs.