N.M. Kannegieter, D.A. Hesselink, R. Kraaijeveld, G.N. de Graav, M.G.H. Betjes, W. Weimar, C.C. Baan
Chair(s): dr. Ron W.F. de Bruin, Erasmus MC, Rotterdam
Thursday 10 march 2016
12:30 - 13:00h at Foyer
Parallel session: Postersessies XI - Opgesplitst in 3 tijdblokken en 3 categoriëen (klinisch, basaal, donatie)
Monocytes have been identified as key players driving rejection processes. Surprisingly, little is known about the effects of immunosuppressive drugs on activation cascades of monocytes during these responses. Here, single-cell phospho-specific flow cytometry was used to explore the effects of immunosuppression on signaling pathways in monocytes of kidney transplant patients.
Patients, materials and methods:
We measured the phosphorylation of the divers signaling pathways including NFκB, MAPK and AKT(mTOR) in peripheral blood CD14+ monocytes of kidney transplant patients (n=14) in the first month after transplantation. Patients received maintenance therapy of tacrolimus, mycophenolate mofetil and prednisone in combination with basiliximab induction therapy.
Before transplantation ex vivo phosphorylation levels of p38MAPK, ERK and AKT, but not of NFκB, were highly expressed by monocytes (MFI: 1863, 635, 1108 and 279 respectively) compared to isotype controls (MFI: 636, 199, 630 and 277, respectively; p<0.001 for p38MAPK, ERK and AKT). After transplantation these phosphorylated signaling molecules were significantly inhibited, 33%, 35% and 19% for p38MAPK, ERK and AKT, p<0.05, respectively. These levels of p38MAPK and AKT, but not of ERK, inversely correlated with tacrolimus pre-dose concentrations (p=0.03 and p=0.01, respectively). No correlation was found between phosphorylated p38MAPK, ERK and AKT levels and kidney function, i.e. serum creatinine or eGFR levels. Remarkably, p38MAPK phosphorylation levels before transplantation were significantly higher in patients suffering from a rejection episode than in patients without a rejection (p=0.03).
The decreased phosphorylation levels of p38MAPK, ERK and AKT after transplantation demonstrate that currently prescribed immunosuppressive drugs also inhibit early monocyte activation.