LAUSR

Plasma concentrations of Torque teno virus (TTV) have been proposed as a biomarker of immune function, which could aid in personalized dosing of immunosuppressive medication after solid organ transplantation. It has been suggested that after replication, TTV enters the circulation through release from leukocytes, particularly granulocytes, or cells within the bone marrow. We hypothesize that leucocyte subpopulations are associated with circulating plasma TTV concentrations in kidney transplant recipients (KTR). We therefore aimed to explore the association of leucocyte subpopulations with plasma TTV concentrations in KTR. A total of 350 KTR with both detectable TTV load and leukocyte population counts at 1 year post-transplantation were selected from the TransplantLines Biobank and Cohort Study. TTV load was measured by real-time PCR assay (TTV R-GENE®, bioMérieux) and leukocyte populations were counted by a Sysmex XN hematology analyzer. Linear regression analyses were performed to assess associations between leukocyte populations and TTV load. Mean age of the included KTR was 56.3 ± 14.5 years, and 133 (38.0%) were female. In multivariable regression analysis, after adjusting for age, sex, smoking behavior, alcohol intake, C-reactive protein, tacrolimus and mycophenolic acid trough levels, and other granulocyte subpopulations, we found that immature granulocyte count was positively associated with TTV load (st. β = 0.44, P < 0.001) and neutrophil count was negatively associated with TTV load (st. β = −0.39, P < 0.001). These results support the theory that TTV replicates in immature granulocytes. The mechanism underlying the negative association between neutrophiles and TTV load remains to be determined. Potential explanations include the suppression of TTV load by antiviral properties of neutrophiles or the possibility that TTV affects the lifespan of neutrophiles. Understanding these relationships might improve the interpretation of TTV load as a marker of immune function in clinical practice.