Link to DOI – 10.1681/ASN.2020040433
J Am Soc Nephrol . 2021 Feb;32(2):479-494
Antibody-mediated rejection (AMR) is a major cause of kidney transplant failure, but individual outcomes are highly heterogeneous. In patients whose donor-specific antibodies (DSAs) do not activate complement, recruitment of innate immune effectors, in particular natural killer (NK) cells, mediates graft destruction. Combining observations from a cohort of kidney transplant recipients with AMR, transcriptomic data, and the use of in vitro models, this translational study demonstrates that the capacity of the recipient’s NK cells to sense absence of self HLA-I molecules (i.e., missing self) on graft vasculature synergizes with DSA-dependent NK cell activation to worsen the outcome of complement-independent chronic AMR. Thus, screening for missing self could help to stratify risk of graft failure and guide a personalized therapeutic approach in AMR.