Torque teno virus monitoring for precision immunosuppression in systemic autoimmune diseases

Systemic autoimmune diseases often require long-term immunosuppression to control disease activity and prevent organ damage. However, immunosuppressive drugs increase the risk of infections, which remain among the leading causes of hospitalization and premature mortality in these conditions. The persistent therapeutic dilemma between too low and too severe immunosuppression is a major challenge in rheumatology practice, and very few tools exist to evaluate and follow the degree of immunosuppression in patients with systemic autoimmune diseases. Torque teno virus (TTV) is a non-pathogenic single-stranded DNA virus, which infects virtually everybody. TTV has emerged as a candidate biomarker of the net state of immunosuppression. TTV replication is dynamically constrained by host immune surveillance; blood viral load rises when immune control is impaired and falls when immune competence is restored. In solid organ transplantation, high TTV loads have been associated with infectious complications, whereas low loads have been associated with graft rejection, supporting the concept that TTV reports the balance between over- and under-immunosuppression. This Review summarizes the biological rationale for TTV monitoring, critically appraises transplantation evidence, reviews emerging data in systemic autoimmune disease, and proposes a translational framework for TTV-guided precision immunomodulation in systemic autoimmune diseases to be evaluated in future studies.