PMID- 28508247
OWN - NLM
STAT- MEDLINE
DCOM- 20180724
LR  - 20181113
IS  - 1573-2584 (Electronic)
IS  - 0301-1623 (Linking)
VI  - 49
IP  - 9
DP  - 2017 Sep
TI  - In human cell cultures, everolimus is inferior to tacrolimus in inhibiting 
      cellular alloimmunity, but equally effective as regards humoral alloimmunity.
PG  - 1691-1697
LID - 10.1007/s11255-017-1615-x [doi]
AB  - PURPOSE: Acute cellular rejection is the major cause of immune-mediated graft 
      failure early in the course of kidney transplantation, whereas chronic 
      antibody-mediated rejection is a major contributor to graft loss in the late 
      post-transplant phase. Based mainly on the results of short-term studies, the 
      calcineurin inhibitor tacrolimus prevails over the mammalian target of rapamycin 
      (mTOR) inhibitors. However, the toxicity profile of the two drug categories 
      differs, making the interchange between them appealing. In this study, the effect 
      of tacrolimus and of the mTOR inhibitor everolimus on cellular and humoral 
      alloimmunity was evaluated. METHODS: Cellular alloimmunity was assessed by cell 
      proliferation in two-way mixed lymphocyte reaction (MLR) with human peripheral 
      blood mononuclear cells (PBMC). For assessing humoral alloimmunity, we developed 
      a method in which humoral alloimmunity was induced in a one-way MLR. The de novo 
      production of alloantibodies was measured with an antibody-mediated 
      complement-dependent cytotoxicity assay, in which supernatants from the above 
      MLRs were used against resting PBMC similar to the stimulator cells of the 
      forementioned MLRs. Tacrolimus and everolimus were used at concentrations near 
      their upper recommended trough levels. RESULTS: In two-way MLRs, tacrolimus 
      inhibited cell proliferation more than everolimus. In one-way MLRs, tacrolimus 
      and everolimus decreased alloantibody production to the same extent. CONCLUSIONS: 
      In human cell cultures, everolimus is inferior to tacrolimus in inhibiting 
      cellular alloimmunity, but equally effective as regards humoral alloimmunity. 
      Thus, everolimus might be a safe alternative in case of tacrolimus toxicity, 
      particularly after the early period of kidney transplantation.
FAU - Eleftheriadis, Theodoros
AU  - Eleftheriadis T
AUID- ORCID: 0000-0001-9302-1633
AD  - Department of Nephrology, Faculty of Medicine, University of Thessaly, Neo 
      Ktirio, Mezourlo Hill, 411 10, Larissa, Greece. teleftheriadis@yahoo.com.
FAU - Pissas, Georgios
AU  - Pissas G
AD  - Department of Nephrology, Faculty of Medicine, University of Thessaly, Neo 
      Ktirio, Mezourlo Hill, 411 10, Larissa, Greece.
FAU - Sounidaki, Maria
AU  - Sounidaki M
AD  - Department of Nephrology, Faculty of Medicine, University of Thessaly, Neo 
      Ktirio, Mezourlo Hill, 411 10, Larissa, Greece.
FAU - Antoniadi, Georgia
AU  - Antoniadi G
AD  - Department of Nephrology, Faculty of Medicine, University of Thessaly, Neo 
      Ktirio, Mezourlo Hill, 411 10, Larissa, Greece.
FAU - Antoniadis, Nikolaos
AU  - Antoniadis N
AD  - Organ Transplant Unit, Hippokration General Hospital, Faculty of Medicine, 
      Aristotle University of Thessaloniki, 546 42, Thessaloniki, Greece.
FAU - Liakopoulos, Vassilios
AU  - Liakopoulos V
AD  - Department of Nephrology, Faculty of Medicine, University of Thessaly, Neo 
      Ktirio, Mezourlo Hill, 411 10, Larissa, Greece.
FAU - Stefanidis, Ioannis
AU  - Stefanidis I
AD  - Department of Nephrology, Faculty of Medicine, University of Thessaly, Neo 
      Ktirio, Mezourlo Hill, 411 10, Larissa, Greece.
LA  - eng
PT  - Comparative Study
PT  - Journal Article
DEP - 20170515
PL  - Netherlands
TA  - Int Urol Nephrol
JT  - International urology and nephrology
JID - 0262521
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Isoantibodies)
RN  - 9HW64Q8G6G (Everolimus)
RN  - WM0HAQ4WNM (Tacrolimus)
SB  - IM
MH  - Adult
MH  - Cell Proliferation/*drug effects
MH  - Cells, Cultured
MH  - Everolimus/*pharmacology
MH  - Humans
MH  - Immunity, Cellular/*drug effects
MH  - Immunity, Humoral/*drug effects
MH  - Immunosuppressive Agents/*pharmacology
MH  - Isoantibodies/metabolism
MH  - Leukocytes, Mononuclear
MH  - Lymphocyte Culture Test, Mixed
MH  - Tacrolimus/*pharmacology
OTO - NOTNLM
OT  - Cellular alloimmunity
OT  - Everolimus
OT  - Humoral alloimmunity
OT  - Tacrolimus
OT  - Transplantation
EDAT- 2017/05/17 06:00
MHDA- 2018/07/25 06:00
CRDT- 2017/05/17 06:00
PHST- 2017/03/12 00:00 [received]
PHST- 2017/05/09 00:00 [accepted]
PHST- 2017/05/17 06:00 [pubmed]
PHST- 2018/07/25 06:00 [medline]
PHST- 2017/05/17 06:00 [entrez]
AID - 10.1007/s11255-017-1615-x [pii]
AID - 10.1007/s11255-017-1615-x [doi]
PST - ppublish
SO  - Int Urol Nephrol. 2017 Sep;49(9):1691-1697. doi: 10.1007/s11255-017-1615-x. Epub 
      2017 May 15.