Background: Blood levels of the ubiquitous but non-pathogenic anellovirus (AnV) taxa have been postulated to represent a biomarker of the overall state of immunosuppression after transplantation. Prior studies, largely cross-sectional in adults, suggest that levels of the AnV rise with major infection events (MIE) and drop with acute rejection (AR).
Objective:The objective was to study the anellovirus trends with MIE and AR events in PKTx
Design/Methods: We have performed longitudinal biobanking of serum in our PKTx population since 2013, combined with monthly testing for opportunistic viruses DNA by PCR from months 1-12 post-transplant and recording of clinical events. In this study we assayed longitudinal biobanked and prospective serum samples for AnV DNA levels (copies/mL) and associated to standard of care monitoring and clinical results. To adjust for repeated measurements within subjects, we used a linear mixed model approach to test for differences in AnV DNA levels between complication groups (None, MIE at time of sample, AR at time of sample). A log transformation was used to better meet model assumptions, and results are reported on the log scale.
Results: In 271 plasma samples from 46 children (Males 52%, white 83%, deceased donor 69%), as shown in Figure, most serum samples are positive for AnV through all time points. Further, box plots of longitudinal results in Figure show a slight increase in median AnV DNA levels at 2-4 months, the peak time period for opportunistic viral replication. Mixed model results showed that the log AnV DNA (copies/mL) was elevated by 0.5 log for the MIE group (adjusted mean of 17.3 [95% CI, 16.1 to 18.4]) compared to the no complications group (adjusted mean of 16.8 [95% CI, 15.9 to 17.7]) (P=0.41). In contrast, results for the AR group showed a lowering of log AnV DNA (copies/mL) (14.3 [95% CI, 15.9 to 17.7]) by 2.5 log compared to the no complications group (P=0.12). Although neither result was statistically significant (likely due to small sample size), both results are consistent with the concept from cross-sectional studies of AnV load as an immunosuppression state biomarker.

Conclusion(s): In our PKTx cohort, our results suggest that longitudinal AnV levels that account for within patient variability also seem to associate to AR and MIE events. Further prospective longitudinal testing in a larger multicenter cohort is recommended.