The measurement of TTV load is a novel, innovative and holistic concept that allows for global assessment of the immune system and, thus, goes beyond state of the art. There have been no major improvements in immunosuppressive drug efficacy and safety realised in the recent years and no novel compounds are on the horizon. The personalisation of existing drugs is a novel and innovative concept in solid organ transplantation though. Thus, the optimisation of drugs via TTV personalisation is a promising strategy.
In Europe, the prevalence of kidney transplantation recipients is 500k and the incidence of kidney transplantation is 30k per year. The percentage of patients suffering from clinically relevant infections is 10% per year and the 5-year death rate is 10%, with 15% of deaths due to infections. The 5-year graft loss rate is 20%, with 50% lost due to rejection, and the percentage of patients suffering from acute rejection in the first year after transplantation is 15%. In total, 50k kidney transplant recipients suffer from infections and 1500 die due to infection each year, 3000 kidney grafts are lost due to rejection per year in the first 5 years and 4000 patients experience acute rejection within the first year after transplantation in Europe. The anticipated 20% reduction in rejection and infection rates by TTV-guided immunosuppression would prevent 10k infections, 300 deaths due to infection, 800 rejections and 600 graft losses in Europe per year.
Lower infection and rejection rates achieved through optimisation of immunosuppression will result in reduced hospitalisation and harm due to the side effects of antimicrobial and anti-rejection therapy. The prolongation of graft survival reduces the need for dialysis, which is a very burdensome procedure for ESRD patients, and thus improvs quality of life. Improved graft survival would also reduce the number of patients re-entering the waiting-list for a kidney transplant after terminal graft failure, thereby shortening the waiting- time for ESRD patients on the waiting list for a suitable kidney. These changes would result in significant improvement in health-related quality of life for ESRD patients.
The assessment of an individual patient’s immune function enables their clinician to personalise immunosuppression, thereby benefiting patients with ESRD. Moreover, the project will act as a proof of principle for TTV-guided immunosuppression and thus pave the way for broader clinical application: for example, emerging oncologic therapies, including checkpoint inhibitors that enhance the immune function and thus control tumor growth, or biological disease-modifying agents in rheumatologic disease might also benefit from TTV guidance. In addition, TTV-guided therapy might be applicable to transplantation of other solid organs, including heart, lung and liver. Immunosuppressed transplant recipients represent one of the most fragile cohorts when it comes to emerging, community-acquired respiratory viruses, since even mild pathogens can replicate if they are not kept in control by the immune system.
