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NON-INVASIVE IMMUNE MONITORING OF PERFORIN/GRANZYME B IN PERIPHERAL BLOOD MAY PREDICT RENAL ALLOGRAFT REJECTION.
Leonard W. Liang, MD , Qiuheng Zhang MD, PhD , David Gjertson PhD , H. Albin Gritsch MD and Elaine F. Reed . Los Angeles CA, University of California Los Angeles, 90049, Immunogenetics .

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Despite improvements in immunosuppression, allograft rejection remains a problem in renal transplantation. Monitoring serum creatinine is of poor prognostic value in predicting acute rejection. Renal allograft biopsy is invasive and predisposes the patient to serious complications. Immune monitoring may provide an early and non-invasive means for identifying patients at risk of acute (AR) and chronic rejection. Fifty-five renal allograft recipients were monitored following transplantation for expression of T cell activation markers in the peripheral blood. Samples were collected weekly during the first 8 weeks and then at weeks 13, 18, 26, 39 and 52. Gene expression of perforin and granzyme B was quantitated by Real-Time PCR and results reported as normalized values to the endogenous control. Assay results were correlated with histologic changes in the renal biopsy and clinical data. In 4 patients with biopsy confirmed AR, mean expression of granzyme B during the first month post-transplantation (122) was significantly elevated compared to patients without evidence of rejection (51) (p<0.006). Similarly, expression of perforin was higher in patients with AR (115) compared to non-rejectors (50) (p<0.003). Expression of perforin (141) and granzyme B (127) was highest during the time of rejection, which was set as one week before and after a positive biopsy. In 2 patients with AR, elevations in perforin and granzyme B gene expression preceded increases in serum creatinine. The data indicate that a program of immune monitoring may serve as a noninvasive aid in the diagnosis of acute rejection..