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@ARTICLE{Reineke:287650,
      author       = {M. Reineke and C. Morath and C. Speer and M. Rudek and C.
                      Bundschuh and J. A. F. Klein and C. F. Mahler and F. Kälble
                      and C. Nusshag and J. Beimler and M. Zeier and R.
                      Bartenschlager$^*$ and P. Schnitzler and L. Benning},
      title        = {{D}ynamics of torque teno virus load in kidney transplant
                      recipients with indication biopsy and therapeutic
                      modifications of immunosuppression.},
      journal      = {Frontiers in medicine},
      volume       = {11},
      issn         = {2296-858X},
      address      = {Lausanne},
      publisher    = {Frontiers Media},
      reportid     = {DKFZ-2024-00293},
      pages        = {1337367},
      year         = {2024},
      abstract     = {Following kidney transplantation, lifelong
                      immunosuppressive therapy is essential to prevent graft
                      rejection. On the downside, immunosuppression increases the
                      risk of severe infections, a major cause of death among
                      kidney transplant recipients (KTRs). To improve
                      post-transplant outcomes, adequate immunosuppressive therapy
                      is therefore a challenging but vital aspect of clinical
                      practice. Torque teno virus load (TTVL) was shown to reflect
                      immune competence in KTRs, with low TTVL linked to an
                      elevated risk for rejections and high TTVL associated with
                      infections in the first year post-transplantation. Yet,
                      little is known about the dynamics of TTVL after the first
                      year following transplantation and how TTVL changes with
                      respect to short-term modifications in immunosuppressive
                      therapy. Therefore, we quantified TTVL in 106 KTRs with 108
                      clinically indicated biopsies, including 65 biopsies
                      performed >12 months post-transplantation, and correlated
                      TTVL to histopathology. In addition, TTVL was quantified at
                      7, 30, and 90 days post-biopsy to evaluate how TTVL was
                      affected by changes in immunosuppression resulting from
                      interventions based on histopathological reporting. TTVL was
                      highest in patients biopsied between 1 and 12 months
                      post-transplantation (N = 23, median 2.98 × 107 c/mL)
                      compared with those biopsied within 30 days (N = 20, median
                      7.35 × 103 c/mL) and > 1 year post-transplantation (N = 65,
                      median 1.41 × 104 c/mL; p < 0.001 for both). Patients with
                      BK virus-associated nephropathy (BKVAN) had significantly
                      higher TTVL than patients with rejection (p < 0.01) or other
                      pathologies (p < 0.001). When converted from mycophenolic
                      acid to a mTOR inhibitor following the diagnosis of BKVAN,
                      TTVL decreased significantly between biopsy and 30 and 90
                      days post-biopsy (p < 0.01 for both). In KTR with high-dose
                      corticosteroid pulse therapy for rejection, TTVL increased
                      significantly between biopsy and 30 and 90 days post-biopsy
                      (p < 0.05 and p < 0.01, respectively). Of note, no
                      significant changes were seen in TTVL within 7 days of
                      changes in immunosuppressive therapy. Additionally, TTVL
                      varied considerably with time since transplantation and
                      among individuals, with a significant influence of age and
                      BMI on TTVL (p < 0.05 for all). In conclusion, our findings
                      indicate that TTVL reflects changes in immunosuppressive
                      therapy, even in the later stages of post-transplantation.
                      To guide immunosuppressive therapy based on TTVL, one should
                      consider inter- and intraindividual variations, as well as
                      potential confounding factors.},
      keywords     = {immune monitoring (Other) / immunosuppression (Other) /
                      kidney transplantation (Other) / precision medicine (Other)
                      / torque teno virus (Other)},
      cin          = {F170 / D430},
      ddc          = {610},
      cid          = {I:(DE-He78)F170-20160331 / I:(DE-He78)D430-20160331},
      pnm          = {314 - Immunologie und Krebs (POF4-314)},
      pid          = {G:(DE-HGF)POF4-314},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:38327708},
      pmc          = {pmc:PMC10847215},
      doi          = {10.3389/fmed.2024.1337367},
      url          = {https://inrepo02.dkfz.de/record/287650},
}