Longitudinal analysis of the impact of rituximab on circulating EBV miRNAs in three paediatric kidney transplant recipients

Abstract

Background: EBV DNA monitoring is currently the main strategy to identify renal transplant recipients potentially at risk of EBV complications. EBV miRNA expression is markedly altered in different disease presentations associated with EBV. We performed a longitudinal assessment of the impact of rituximab on circulating EBV miRNA in 3 paediatric kidney transplant recipients. Methods: Forty-two miRNAs encoded within 2 EBV open reading frames (BART and BHRF) were examined over a 28-month period using miRNA qPCR custom panels. EBV DNA was measured using qPCR and lymphocyte subsets were measured by flow cytometry. Results: Patients were 3 years post kidney transplant and received cycles of rituximab infusions. Treatment with rituximab caused an immediate depletion of the circulating B cells and reduced the expression of the miRNAs and EBV DNA levels. About 4 months post treatment, as the circulating B cells repopulated, EBV miRNAs levels increased. A total of 29 plasma samples were studied and between 4 and 34 EBV miRNAs were detected. A significant correlation was observed between the numbers of EBV miRNAs expressed and the EBV DNA level (r = 0.63, p = 0.001). Conclusion: We provide an in-depth longitudinal assessment of the impact of rituximab on specific circulating EBV miRNA expression in three paediatric kidney transplant recipients. Rituximab treatment resulted in the reduction of EBV miRNA expression and EBV DNA viral loads. Larger studies are required to determine whether EBV miRNA levels could be useful biomarkers to predict transplant recipients at risk of developing post-transplant lymphoproliferative disease.

Keywords

• EBV miRNAs
• Rituximab
• Paediatric kidney transplant
• B cells