Perforin A and granzyme B as non invasive markers in early acute rejection in pediatric renal transplantation

Introduction: Identification of new noninvasive sensitive markers that can predict acute rejection (AR) will provide a better chance for early therapeutic intervention before full clinical picture of AR with its consequences had occurred. We aimed to measure perforin A and granzyme B mRNA levels in serum and urine of children underwent recent renal transplantation during the first three months after transplantation. Methods: The study included 69 recently transplanted pediatric patients and 40 age and sex matched normal subjects. Quantification of perforin A and granzyme B expression using quantitative reverse transcriptase real time PCR, was done at 1 week, 1 month and 3 months after transplantation. Patients were followed up for development of AR during their first 3 months. Results: Twelve patients developed AR (rejecters) and 57 patients did not develop AR (non-rejecters). Rejecters showed significantly elevated levels of perforin A and granzyme B expression in pre-rejection blood and urine samples (at 1st week and 1st month), compared to non-rejecter group (p < 0.001 for all comparisons). ROC curve analysis suggested that assessment of perforin A and granzyme B expression at 1 week and 1 month post transplantation could be predictor markers for early AR with high discriminative power (AUC ranged between 0.79 and 0.98). Conclusions: Early measurements of perforin A and granzyme B expression in blood and urine after renal transplantation could identify pediatric patients at risk of AR, suggesting these patients as candidates for biopsy or for initiation of anti-rejection therapy.