PMID- 35213773
OWN - NLM
STAT- MEDLINE
DCOM- 20220407
LR  - 20220407
IS  - 1399-3062 (Electronic)
IS  - 1398-2273 (Linking)
VI  - 24
IP  - 2
DP  - 2022 Apr
TI  - Viral-specific cytotoxic T-cell responses in HLA-sensitized kidney transplant 
      patients maintained on everolimus and low-dose tacrolimus.
PG  - e13805
LID - 10.1111/tid.13805 [doi]
AB  - BACKGROUND: Maintenance with "everolimus + reduced dose tacrolimus" (Ev + 
      Tac(low) ) was reported to reduce the risk of viral infections compared to 
      "tacrolimus + mycophenolate mofetil" (Tac + MMF). Here we examined viremia and 
      viral-specific T-cell (viral-Tc) responses in patients treated with Ev + Tac(low) 
      versus Tac + MMF in highly-human leukocyte antigen (HLA)-sensitized patients. 
      METHODS: HLA-sensitized (HS) kidney transplant patients were monitored pre- and 
      post-transplant for viremia (cytomegalovirus (CMV), BK, and Epstein-Barr virus 
      (EBV)) by polymerase chain reaction (PCR) in 19 Ev + Tac(low) and 48 Tac + MMF 
      patients. For CMV PCR analysis, we compared infection rates in 19 Ev + Tac(low) 
      patients to 48 CMV D+/R- (#28) or CMV D-/R- (#20) Tac + MMF patients. 
      CMV-specific cytotoxic T cell (CMV-Tc) and EBV-specific cytotoxic T cell (EBV-Tc) 
      were evaluated by cytokine flow cytometry, and donor-specific antibody (DSA) 
      levels by Luminex for selected patients in both groups. RESULTS: CMV and EBV 
      viremia rates were similar in Ev + Tac(low) versus Tac + MMF patients, but BK 
      virus (BKV) rates were significantly higher in Ev + Tac(low) patients. No patient 
      in either group developed BK virus-associated allograft nephropathy (BKAN) or 
      post-transplant lymphoproliferative disorders (PTLD). CMV-Tc and EBV-Tc decreased 
      significantly after alemtuzumab induction but returned to pre-treatment levels 
      1-2 months post-transplant in most patients. de novo DSA was similar in both 
      groups as were patient and graft survival and graft rejection. CONCLUSIONS: 
      CMV-Tc and EBV-Tc were similar in Ev + Tac(low) and Tac + MMF patients. EBV and 
      CMV viremia rates were similar over 1 year. BKV rates were significantly higher 
      in Ev + Tac(low) patients suggesting no benefit for Ev + Tac(low) in enhancing 
      viral-Tc effector functions or limiting viral infections.
CI  - (c) 2022 Wiley Periodicals LLC.
FAU - Ge, Shili
AU  - Ge S
AD  - Transplant Immunology Laboratory, Cedars-Sinai Medical Center, Los Angeles, 
      California, USA.
FAU - Chu, Maggie
AU  - Chu M
AD  - Transplant Immunology Laboratory, Cedars-Sinai Medical Center, Los Angeles, 
      California, USA.
FAU - Tang, Jacqueline
AU  - Tang J
AD  - Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, 
      California, USA.
FAU - Kahwaji, Joseph
AU  - Kahwaji J
AD  - Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, 
      California, USA.
FAU - Karasyov, Artur
AU  - Karasyov A
AD  - Transplant Immunology Laboratory, Cedars-Sinai Medical Center, Los Angeles, 
      California, USA.
FAU - Lovato, Darly
AU  - Lovato D
AD  - Transplant Immunology Laboratory, Cedars-Sinai Medical Center, Los Angeles, 
      California, USA.
FAU - Vo, Ashley
AU  - Vo A
AD  - Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, 
      California, USA.
FAU - Choi, Jua
AU  - Choi J
AD  - Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, 
      California, USA.
FAU - Jordan, Stanley C
AU  - Jordan SC
AD  - Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, 
      California, USA.
FAU - Zhang, Ruan
AU  - Zhang R
AUID- ORCID: 0000-0003-2297-6613
AD  - Transplant Immunology Laboratory, Cedars-Sinai Medical Center, Los Angeles, 
      California, USA.
FAU - Toyoda, Mieko
AU  - Toyoda M
AD  - Transplant Immunology Laboratory, Cedars-Sinai Medical Center, Los Angeles, 
      California, USA.
LA  - eng
GR  - Novartis Institute for Biomedical Research/
PT  - Journal Article
DEP - 20220303
PL  - Denmark
TA  - Transpl Infect Dis
JT  - Transplant infectious disease : an official journal of the Transplantation 
      Society
JID - 100883688
RN  - 0 (Immunosuppressive Agents)
RN  - 9HW64Q8G6G (Everolimus)
RN  - HU9DX48N0T (Mycophenolic Acid)
RN  - WM0HAQ4WNM (Tacrolimus)
SB  - IM
MH  - *Epstein-Barr Virus Infections/drug therapy
MH  - Everolimus/therapeutic use
MH  - Graft Rejection
MH  - Herpesvirus 4, Human
MH  - Humans
MH  - Immunosuppressive Agents/therapeutic use
MH  - *Kidney Transplantation/adverse effects
MH  - Mycophenolic Acid/therapeutic use
MH  - T-Lymphocytes
MH  - Tacrolimus/therapeutic use
OTO - NOTNLM
OT  - BKV
OT  - CMV
OT  - EBV
OT  - HLA sensitized
OT  - everolimus
OT  - kidney transplant
OT  - tacrolimus
EDAT- 2022/02/26 06:00
MHDA- 2022/04/08 06:00
CRDT- 2022/02/25 17:17
PHST- 2022/01/21 00:00 [revised]
PHST- 2021/10/13 00:00 [received]
PHST- 2022/01/31 00:00 [accepted]
PHST- 2022/02/26 06:00 [pubmed]
PHST- 2022/04/08 06:00 [medline]
PHST- 2022/02/25 17:17 [entrez]
AID - 10.1111/tid.13805 [doi]
PST - ppublish
SO  - Transpl Infect Dis. 2022 Apr;24(2):e13805. doi: 10.1111/tid.13805. Epub 2022 Mar 
      3.