% IMPORTANT: The following is UTF-8 encoded. This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.
@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},
}