Antibody-mediated allograft rejection: the emerging role of endothelial cell signalling and transcription factors.

The presence of antibodies against class I human leukocyte antigens (HLA) can cause the development of chronic allograft rejection. Although endothelial cell activation has been identified as a main effector, the mechanisms mediating this process are not fully understood. Exposure of endothelium to antibodies against HLA antigens induces cell activation which promotes rejection. This activation process can be divided into two phases: an early response in which intracellular signalling proteins and transcription factors are activated, and a later change in protein expression and cell function. In this review, antibody-mediated endothelial signalling and the role of transcription factors in organ transplantation will be described with a particular focus on their potential to mediate some of the graft-damaging effects of anti-HLA class I antibodies.