The Activation of mTOR Pathway, a Marker of Endothelial Cell Involvement, Is Correlated with Antibody Mediated Rejection
Marion Tible, Alexandre Loupy, Jean-Paul Duong, Patrick Bruneval. PARCC, Paris, France; Hopital Europeen Georges Pompidou, Paris, France
Background: In cardiac transplantation, the pathological classification of the antibody mediated rejection (AMR) on endomyocardial biopsies (EMB) is based on histology (microvascular inflammation) and immunohistochemistry (deposition of C4d and/or CD68-positive intravascular macrophages). It is ranked in 4 grades, from pAMR0 to pAMR3. pAMR1 which corresponds to a suspicious AMR is divided in two categories: pAMR1(H+) based on histology findings alone and pAMR1(I+) based on immunopathologic findings alone. Previous studies suggested that mTOR pathway activation, detected by in situ microvascular expression of mTOR targets p70 S6 kinase (p70S6K) and phospho-S6 ribosomal protein (pS6RP), could be associated with endothelial cell involvement during AMR. The aim of the study was tocorrelate pS6RP and p70S6K expression with other AMR markers (C4d deposition, CD68-positive intravascular macrophages, and DSA); To assess the diagnostic value of immunohistochemical detection of pS6RP and p70S6K in microvessels of EMB.
Design: 280 protocol EMB harvested during a 1 year period of time in a single institution were used. 37 EMB with pathological features of AMR were included in the pAMR+ group encompassing 27 pAMR1(H+), 1 pAMR(I+), and 9 pAMR2. 37 EMB were randomly selected among the pAMR0 EMB and were included in the control group. Capillary expression of pS6RP and p70S6K was assessed by immunohistochemistry and ranked from grade 0 to grade 4. Only grades 3 and 4 were considered as positive. In parallel DSA were assessed using Luminex technique.
Results: In the pAMR+ group, pS6RP and p70S6K were expressed in the endothelial cells of the EMB ranked pAMR2 (4/9 and 7/9 respectively), and also in grade pAMR1(H+) EMB (3/27 and 10/27 respectively). In the control group 1/37 EMB was positive. Microvascular expression of pS6RP and p70pS6K was correlated with DSA (p<0.01) and microvascular inflammation (p<0.05).
Conclusions: The endothelial expression of mTOR targets pS6RP et p70S6K, markers of endothelial cell activation, is associated with AMR in both definite AMR grade pAMR2 and suspicious AMR grade pAMR1(H+), negative for C4d and CD68. That latter finding underscores the diagnostic value of pS6RP and p70S6K immunohistochemistry to characterize AMR in C4d-negative EMB.
Wednesday, March 6, 2013 9:30 AM
Poster Session V # 49, Wednesday Morning