PHOSPHORYLATED S6 KINASE AND S6 RIBOSOMAL PROTEIN ARE NOVEL BIOMARKERS OF ANTIBODY MEDIATED REJECTION IN HEART ALLOGRAFTS

摘要

Antibody mediated rejection (ARM) is emerging as a leading cause of allograft rejection and graft loss. Anti-HLA antibodies have been implicated in the process of acute and chronic AMR because these antibodies bind to the endothelium of the graft and transduce signals leading to the activation of cell survival and proliferation pathways. Ligation of Class I molecules on the surface of endothelial cells by anti-HLA antibodies activates Src and FAK, stimulates the formation of mTORCl and mT0RC2 and activates downstream targets ERK, S6 kinase and S6 ribosomal protein resulting in cell proliferation. With the availability of phosphorylation-specific antibodies that can detect activated signaling molecules, we tested the hypothesis that phosphorylation of S6 kinase and S6 ribosomal protein would represent biomarkers of antibody mediated rejection of heart allografts.