Objective: To study the roles of granzyme B and perforin in diagnosing acute rejection after liver transplantation, and the relationship between their activity index (AI) and Banff's histological grading criteria.
Methods: Liver biopsies were processed as for routine surgical specimens and labeled with granzyme B and perforin monoclonal antibodies. The number of positive cells/mm(2) was determined as activity index (AI) by IPP image analysis software. Histologic findings were used as the "gold standard" in diagnosing acute rejection.
Results: Of 41 liver biopsy samples studied, acute rejection was noted in 21 cases, the remaining 20 cases showed no evidence of rejection. The AI of granzyme B and perforin in the acute rejection group was significantly higher than that in the non-acute rejection group (< 0.001). In the acute rejection group, the AI in moderate to severe acute rejection was higher than that in mild to indeterminate acute rejection (< 0.001). Compared with the "golden" histologic criteria, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of granzyme B in diagnosing acute rejection were 90.0%, 95.2%, 94.7%, 90.9% and 92.7% respectively. The values of these parameters for perforin were also above 80%.
Conclusions: Granzyme B and perforin are key markers of activated immune cells in acute rejection and highly expressed during acute liver rejection episodes. As ancillary investigations, these parameters demonstrated high sensitivity and specificity in diagnosing acute rejection in allograft post-transplant liver biopsies.