After kidney transplantation (KTx) immunosuppressive therapy causes an impaired cellular immune defense resulting in an increased risk of BKPyV-nephropathy (BKPyVAN). Prognostic markers for the outcome of BKPyV-infections are missing. BKPyV-specific T cells (BKPyV-Tvis)may serve as a diagnostic parameter for the risk of BKPyV-associated complications.

After KTx follow-up of BKPyV-Tvis were analysed in 42 children with current or previous detection of BKPyV-DNA in blood. Leukocytes were stimulated in vitro with BKPyV-antigens (VP1; large T) and immunostained by fluorescent antibodies. Based on specific cellular activation and induction of intracellular cytokine-production, BKPyV-CD4 and CD8 Tvis were identified by flow cytometry. Statistical analysis was performed by Mann Whitney- and Spearman-test.

The majority (39/42) showed -at least temporarily- BKPyV-CD4 Tvis, whereas only 33 patients had BKPyV-CD8 Tvis. Low BKPyV-Tvis were correlated with an increased risk of long-term persistency of BKPyV-DNA (CD4 & CD8 Tvis: Spearman r=-0.37; p<0.0001): BKPyV-Tvis were significantly lower in case of DNA-persistency >120 days (BKPyV-CD4 Tvis 0.4±0.6/[micro]l vs. 1.8±2.2/[micro]l; BKPyV-CD8 Tvis 0.1±0.1/[micro]l vs. 1.5±4.4/[micro]l;p<0.0001). Only 1 out of 26 patients with high levels of BKV-CD4 Tvis (>0.7 cells/[micro]l) showed persistency of blood-BKPyV-DNA longer than 120 days (p<0.0001). Significant detection of BKPyV-CD8 Tvis (>0.4 cells/[micro]l) was only found if BKPyV-DNA disappeared within the following 120 days (p<0.0001). Kidney biopsy of 10 children showed signs of BKPyVAN with nuclear SV40 immunoreactivity. Children with biopsy proven severe BKPyVAN (n=5) were characterized by persistency of blood-BKPyV-DNA (>120 days) combined with lack or low levels of BKPyV-CD4 Tvis (<0.7/[micro]l) and BKPyV-CD8 Tvis (<0.4/[micro]l). After minimization of immunosuppressive therapy BKPyV-CD4 Tvis were increasing simultaneously with decrease of BKPyV-DNA.

In case of BKPyV-DNA-detection in blood, low levels of BKPyV-Tvis are associated with an increased risk of florid BKPyVAN, whereas sufficient BKPyV-Tvis enable to overcome BKPyV-infections without BKPyV-associated complications. Serving as a marker for the individual BKPyV-specific immune defense, levels of BKPyV-Tvis may represent the risk of BKPyVAN and optimize individual therapeutic interventions.

CITATION INFORMATION: Ahlenstiel-Grunow T., Sester M., Sester U., Pape L. BK Polyomavirus (BKPyV)-Specific T Cells as a Diagnostic and Prognostic Marker for BKPyV-Infections after Pediatric Kidney Transplantation Am J Transplant. 2017;17 (suppl 3).

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