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Natural Killer CD16/FcR Profiles May Associate with Enhanced Humoral Responsiveness in Heart Transplant Recipients with Cardiac Allograft Vasculopathy.

P. Paul,1,2 C. Picard,3,4 E. Sampol,5 L. Lyonnet,1 J. Di Cristofaro,3,4 G. Lano,6, B. Dussol,6, F. Collart,7 F. Sabatier,1,2 F. Dignat George,1,2 A. Mouly Bandini.7

1Hematology, Assistance Publique-Hopitaux Marseille (AP-HM), Marseille, France
2UMR-1076, Aix Marseille Université
(AMU), INSERM, Marseille, France
3Établissement Français du Sang, Marseille, France
4UMR7268, AMU, CNRS, Marseille, France
5Pharmacokinetics, AP-HM, Marseille, France
6Center for Clinical Investigation, AP-HM, Marseille, France
7Cardiac Surgery, AP-HM, Marseille, France.

Meeting: 2016 American Transplant Congress

Abstract number: 243

Keywords: Antibodies, Graft failure, Heart transplant patients, Natural killer cells

Session Information

Date: Monday, June 13, 2016

Session Name: Concurrent Session: Molecular and Bio-Markers in Hearts and VADs - A New Hope

Session Time: 2:30pm-4:00pm

 Presentation Time: 2:54pm-3:06pm

Location: Room 102

Related Abstracts
  • Enhanced Natural Killer Responsiveness Is a Potent Cytotoxic Mechanism Associating to Kidney Allograft Dysfunction and Pathogenic Effects of Donor-Specific Antibodies (DSA).
  • Gene Expression Microarray Analysis of Purified CD16-Stimulated Human NK Cells and Indication Biopsies Supports a CD16-Mediated Role for NK Cells in Antibody-Mediated Kidney Rejection.

Natural Killer cells (NK) are immune effectors of antibody-dependent cellular cytotoxicity (ADCC). Their role in mediating adverse effects of Donor-specific anti-HLA antibodies (DSA) towards cardiac allograft remains unexplored. We tested whether FcγRIIIa/CD16 Fc-receptor profiles can be associated with coronary artery vasculopathy (CAV). CD16 expression and polymorphism was evaluated in 103 heart transplant recipients (HTR) enrolled at time of coronary angiography. A cellular humoral activation test (NK-CHAT) was designed to monitor NK-cell activation potential of serum samples obtained during longitudinal follow-up in DSA+ patients. Serum-driven CD16 engagement towards allogeneic cell targets allowed to quantify activity of sera.

Of 103 patients, 53 were diagnosed as CAV+. DSA+ patients (18%) had higher rates of CAV compared with DSA– patients (28 vs 8%, p=0.014). Frequency of the CD16/158VV polymorphic variant (with high-affinity for the Fc Fragment of Ig) was significantly higher in the CAV+ group (25 vs 8%), while that of the low-responsive CD16/158FF variant was higher in the CAV– group (40 vs 7%). Median CD16 expression, analyzed by flowcytometry within peripheral NK cells, was significantly higher in the CAV+ group. Multivariate analysis confirmed that CD16 polymorphism and expression remained significantly associated with CAV. When coated on B-cell targets expressing cognate HLA alloantigens, DSA+ sera exhibited enhanced capacity to engage CD16 and stimulate NK cell cytotoxic functions in vitro, when analyzed in reference with DSA– serum samples obtained before immunisation (p<0.0001). Our study suggests that the potential of HTR to mount CD16-dependent cytotoxic responses may condition intensity of cellular humoral responses, when the allograft graft is chronically challenged with DSA. NK-CHAT non-invasive monitoring may allow identification of patients at higher risk to develop CAV when high humoral scores and CD16 responsiveness are detected.

CITATION INFORMATION: Paul P, Picard C, Sampol E, Lyonnet L, Di Cristofaro J, Lano G, Dussol B, Collart F, Sabatier F, Dignat George F, Mouly Bandini A. Natural Killer CD16/FcR Profiles May Associate with Enhanced Humoral Responsiveness in Heart Transplant Recipients with Cardiac Allograft Vasculopathy. Am J Transplant. 2016;16 (suppl 3).

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To cite this abstract in AMA style:

Paul P, Picard C, Sampol E, Lyonnet L, Cristofaro JDi, Lano G, Dussol B, Collart F, Sabatier F, George FDignat, Bandini AMouly. Natural Killer CD16/FcR Profiles May Associate with Enhanced Humoral Responsiveness in Heart Transplant Recipients with Cardiac Allograft Vasculopathy. [abstract]. Am J Transplant. 2016; 16 (suppl 3). https://atcmeetingabstracts.com/abstract/natural-killer-cd16fcr-profiles-may-associate-with-enhanced-humoral-responsiveness-in-heart-transplant-recipients-with-cardiac-allograft-vasculopathy/. Accessed January 25, 2021.

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