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

Abstract

IntroductionIdentification of new non- invasive 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. MethodsThe 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. ResultsTwelve 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). ConclusionsEarly 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.