Exosomal miRNA expression in transplant recipients with EBV-associated post-transplant lymphoproliferative disorder.

BACKGROUND

Epstein-Barr Virus (EBV) drives the development of EBV-associated malignancies such as post-transplant lymphoproliferative disorder (PTLD), evading immune detection. However, how EBV is able to evade immune surveillance is not well understood. One theory suggests that modulation of host microRNAs (miRNAs) expression can help escape immune recognition. EBV-encoded miRNAs support tumor cells survival and manipulate expression of host miRNAs. EBV-infected cells package their content into exosomes, which are transferred throughout the body. Tumor and infected cells by packaging their oncogenic or viral cargo into exosomes can spread the disease and infection. Exosomal cargo is being recognized as potential non-invasive biomarker.

OBJECTIVES

The aim of this investigation was to analyse the expression of both host- and EBV-encoded miRNAs in exosomes derived from PTLD patients after solid organ transplantation (SOT) or allogeneic hematopoietic stem cell transplantation (HSCT).

PATIENTS AND

METHODS

We examined the expression of 28 miRNAs (13 EBV- and 15 host-encoded) from plasma of 23 patients post-HSCT with PTLD (PTLD-HSCT) and 25 post-HSCT patients without PTLD (Non-PTLD-HSCT) at 3 different timepoints (T0 [at the time of HSCT], T1 [3 months post-HSCT] and T2 [6 months post-HSCT]. We also analyzed plasma of 10 solid organ transplant recipients (SOT) with EBV-positive PTLD (PTLD-SOT-EBV(+)) and 8 with EBV-negative PTLD (PTLS-SOT-EBV(-)) and 25 healthy donors.

RESULTS

There was no difference in miRNAs expression between PTLD-HSCT and Non-PTLD-HSCT group. Significant differences in miRNAs expression between PTLD patients (post-SOT and post-HSCT) and healthy donors was observed. miRNAs profile differed between EBV(+) and EBV(-) PTLD patients.

CONCLUSIONS

We highlight the importance of an intermediate control group for selecting PTLD-specific biomarker. Future research should focus on detailed characterization of additional components of the exosomal cargo to identify reliable and non-invasive biomarkers that are critical and specific for PTLD development.