Enhanced Natural Killer Responsiveness Is a Potent Cytotoxic Mechanism Associating to Kidney Allograft Dysfunction and Pathogenic Effects of Donor-Specific Antibodies (DSA).
1Hematology, Assistance Publique Hopitaux Marseille, Marseille, France
2UMR-1076, VRCM, Aix Marseille University, INSERM, Marseille, France
3Nephrology Dialysis Renal Transplantation Center, Assistance Publique Hopitaux Marseille, Marseille, France
4Immunogenetics, Etablissement Français du Sang, Marseille, France
5Anatomy, Pathology, Neuropathology, Assistance Publique Hopitaux Marseille, Marseille, France
6Center for Clinical Investigation, Assistance Publique Hopitaux Marseille, Marseille, France.
Meeting: 2016 American Transplant Congress
Abstract number: D7
Keywords: Graft function, HLA antibodies, Kidney transplantation, Natural killer cells
Session Information
Session Name: Poster Session D: Antibody Mediated Rejection: Session #2
Session Type: Poster Session
Date: Tuesday, June 14, 2016
Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Halls C&D
While antibody mediated rejection (ABMR) is a major cause of kidney transplant loss, the role of Natural Killer cells (NK) as immune effectors of complement-independent pathogenic effects of DSA remains poorly explored. We investigated whether antibody-dependent NK cell cytotoxicity (NK-ADCC) may associate to allograft dysfunction in kidney transplant recipients (KTR).
A flow cytometry Cellular Humoral Activation Test (NK-CHAT) was designed to evaluate recipient- and DSA-dependent NK-cell activation towards allogeneic cells. Study of peripheral NK-cell cytotoxicity in 148 KTR revealed a high interindividual variability of NK responsiveness. KTR with highest ADCC potential towards Rituximab-coated B-cell targets were at higher risk of eGFR decline one year after inclusion. NK-CHAT evaluation of sera from KTR identified CD16 engagement as a sensitive and specific marker of DSA-dependent NK activation towards HLA antigens that discriminates reactivity of circulating DSA with similar MFI. NK-CHAT could be associated with occurrence of microvascular lesions of ABMR. NK cells recruited in a kidney with ABMR exhibited an activated profile associated to in situ engagement of CX3CR1 and CD16 receptors. DSA-specific NK cell activation was associated with enhanced lysis of glomerular cells and release of procoagulant endothelial microvesicles in vitro.
Collectively, these data suggest that enhanced NK-cell responsiveness may identify individuals with higher potential to elicit graft vascular damage in response to chronic DSA exposition. Through indexing of bifunctional features that may impact complement independent DSA toxicity, ie Fab-ligation of alloantigen and variability in Fc-driven immune triggering, non-invasive NK-CHAT monitoring may allow to refine appraisal of humoral risk on an individual basis.
CITATION INFORMATION: Paul P, Legris T, Picard C, Todorova D, Lyonnet L, Daniel L, Dussol B, Moal V, Vacher Coponat H, Berland Y, Dignat-George F, Burtey S. Enhanced Natural Killer Responsiveness Is a Potent Cytotoxic Mechanism Associating to Kidney Allograft Dysfunction and Pathogenic Effects of Donor-Specific Antibodies (DSA). Am J Transplant. 2016;16 (suppl 3).
To cite this abstract in AMA style:
Paul P, Legris T, Picard C, Todorova D, Lyonnet L, Daniel L, Dussol B, Moal V, Coponat HVacher, Berland Y, Dignat-George F, Burtey S. Enhanced Natural Killer Responsiveness Is a Potent Cytotoxic Mechanism Associating to Kidney Allograft Dysfunction and Pathogenic Effects of Donor-Specific Antibodies (DSA). [abstract]. Am J Transplant. 2016; 16 (suppl 3). https://atcmeetingabstracts.com/abstract/enhanced-natural-killer-responsiveness-is-a-potent-cytotoxic-mechanism-associating-to-kidney-allograft-dysfunction-and-pathogenic-effects-of-donor-specific-antibodies-dsa/. Accessed May 11, 2025.« Back to 2016 American Transplant Congress