A schema for histologic grading of small intestine allograft acute rejection

Background. Histologic evaluation of small bowel allograft biopsies is important for the diagnosis of acute rejection. However, a standard histologic schema to grade the severity of intestinal acute rejection is not currently available. The primary goal of this study was to develop a histologic grading system for the diagnosis of small bowel allograft acute rejection. Methods. We evaluated 3268 small bowel allograft biopsies obtained from adult patients who underwent small bowel transplantation at the University of Pittsburgh Medical Center between 1990 and 1999. A histologic grading system was proposed and validated by retrospective correlation with clinical outcomes. Results. Among the 3268 biopsies, 180 acute rejection episodes were diagnosed (88 indeterminate, 74 mild, 14 moderate, and 4 severe). All four histologically diagnosed, severe acute rejection episodes resulted in graft failure before resolution, despite aggressive immunosuppressive therapy. Four of the 14 moderate acute rejection episodes were associated with unfavorable clinical outcomes. In contrast, the 74 mild and 88 indeterminate acute rejection episodes were not associated with unfavorable clinical outcomes. Statistical analysis for trend revealed that grades indicating more severe acute rejection episodes were associated with a greater probability of unfavorable outcomes (P<0.01). In addition, there was good overall agreement among different pathologists regarding the diagnosis of acute rejection using the proposed schema, suggesting that this system is practical. Conclusions. This study provides a reliable predictive schema for assessment of the severity of human small bowel acute rejection.