Monitoring Human Immune Competence Using a Symbiont Virus: From Bench to Bedside

Monitoring immune competence in transplant recipients would help tailor-made induction and maintenance immunosuppression: to date, no comprehensive test is available on the market. Torquetenovirus (TTV) is an orphan human virus with > 95% prevalence worldwide. Once acquired, it establishes chronic viremia (approximatively 3 log10 in healthy donors), which goes up to > 5 logs in every condition of immune suppression. Since 2008, our group first reported kinetics of TTV in myeloma and lymphoma patients receiving high-dose chemotherapy supported by autologous hematopoietic stem cell transplantation (Focosi et al, Transplantation, 2008). The clinical utility of TTV viremia determination was promptly shown by correlation with opportunistic CMV reactivations, and ability to predict time needed for return to normal immune competence. A very recent work (de Vlaminck et al, Cell, 2013) has shown that TTV is the only virus in the human plasma virome whose load changes significantly after heart or lung transplantation. The authors used shotgun sequencing, a very costly technique unapt for routine diagnostic use. We report here a single-centre, prospective trial enrolling 100 orthotopic liver transplant recipients and 100 kidney and/or pancreas transplant recipients followed-up for 2 years. Plasma samples were collected before transplantation, and at months 1, 3, 6, 12, and 24. A cheap, simple, universal real-time PCR was used to determine overall TTV viremia. Liver transplant recipients were stratified according to the intensity of maintenance immune suppression. Kidney and/or pancreas transplant recipients were stratified according to intensity of induction immune suppression. We report a significant association between TTV viremia and CMV reactivations, and biopsy-proven graft rejection. In conclusion, our data support the emerging concept that this marker can be of help for noninvasively confirm the clinical suspicion of graft rejection.