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© Research
Publication : Journal of the American Society of Nephrology

Missing Self-Induced Activation of NK Cells Combines with Non-Complement-Fixing Donor-Specific Antibodies to Accelerate Kidney Transplant Loss in Chronic Antibody-Mediated Rejection

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Journal of the American Society of Nephrology - 12 Dec 2020

Alice Koenig, Sarah Mezaache, Jasper Callemeyn, Thomas Barba, Virginie Mathias, Antoine Sicard, Béatrice Charreau, Maud Rabeyrin, Frédérique Dijoud, Cécile Picard, Vannary Meas-Yedid, Jean-Christophe Olivo-Marin, Emmanuel Morelon, Maarten Naesens, Valérie Dubois and Olivier Thaunat

Link to DOI – 10.1681/ASN.2020040433

JASN November 2020

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.

https://jasn.asnjournals.org/content/early/2020/11/25/ASN.2020040433