LAUSR

There is a growing body of literature linking non-HLA antibodies to acute and chronic allograft injury across all transplanted organ types (1). Even more striking is the injury potential observed when non-HLA antibodies are detected simultaneously with donor-specific HLA antibodies (2). The vascular endothelium serves as the primary barrier between the patient's immune system and the transplanted allograft; therefore, understanding how bound antibodies affect endothelial cells (EC) has been a long-standing topic of interest (Figure 1). EC dysfunction associated with non-HLA antibodies include hypercoagulability, activation and increased permeability, apoptosis, and in some cases complement activation (2, 3). The effector functions of non-HLA antibodies reflect intrinsic characteristics corresponding to titer, affinity, and isotype as well as extrinsic factors such as the non-HLA target antigen and its expression density within different allograft tissues. All of these factors contribute to the injury potential and the observed injury phenotypes associated with non-HLA antibodies. Therefore, we may need to rethink our definitions for antibody mediated rejection when facilitated by non-HLA antibodies, given that EC dysfunction and allograft injury may be mediated through mechanistic pathways that differ from HLA antibodies.