{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T12:11:18Z","timestamp":1790424678581,"version":"4.1.0"},"reference-count":35,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2018,3,6]]},"abstract":"<jats:sec>\n            <jats:title>Background:<\/jats:title>\n            <jats:p>Cardiac transplantation is an effective therapy for end-stage heart failure. Because cardiac allograft vasculopathy (CAV) is the major cause of late mortality after heart transplant (HT), there is a need to identify markers that reflect inflammatory or cytotoxic immune mechanisms contributing to its onset. Noninvasive and early stratification of patients at risk remains a challenge for adapting individualized therapy. The CD16 (Fc-gamma receptor 3A [FCGR3A]) receptor was recently identified as a major determinant of antibody-mediated natural killer (NK) cell activation in HT biopsies; however, little is known about the role of CD16 in promoting allograft vasculopathy. This study aimed to investigate whether markers that reflect CD16-dependent circulating NK cell activation may identify patients at higher risk of developing CAV after HT.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods:<\/jats:title>\n            <jats:p>Blood samples were collected from 103 patients undergoing routine coronarography angiography for CAV diagnosis (median 5 years since HT). Genomic and phenotypic analyses of FCGR3A\/CD16 Fc-receptor profiles were compared in CAV-positive (n=52) and CAV-free patients (n=51). The levels of CD16 expression and rituximab-dependent cell cytotoxic activity of peripheral NK cells in HT recipients were evaluated using a noninvasive NK-cellular humoral activation test.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results:<\/jats:title>\n            <jats:p>\n              Enhanced levels of CD16 expression and antibody-dependent NK cell cytotoxic function of HT recipients were associated with the FCGR3A-VV genotype. The frequency of the FCGR3A-VV genotype was significantly higher in the CAV\n              <jats:sup>+<\/jats:sup>\n              group (odds ratio, 3.9;\n              <jats:italic>P<\/jats:italic>\n              =0.0317) than in the CAV\n              <jats:sup>-<\/jats:sup>\n              group. The FCGR3A-VV genotype was identified as an independent marker correlated with the presence of CAV at the time of coronary angiography by using multivariate logistic regression models. The FCGR3A-VV genotype was also identified as a baseline-independent predictor of CAV risk (odds ratio, 4.7;\n              <jats:italic>P<\/jats:italic>\n              =0.023).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>This study unravels a prominent role for the CD16-dependent NK cell activation pathway in the complex array of factors that favor the progression of transplant arteriosclerosis. It highlights the clinical potential of a noninvasive evaluation of FCGR3A\/CD16 in the early stratification of CAV risk. The recognition of CD16 as a major checkpoint that controls immune surveillance may promote the design of individualized NK cell\u2013targeted therapies to limit vascular damage in highly responsive sensitized patients.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Clinical Trial Registration:<\/jats:title>\n            <jats:p>\n              URL:\n              <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\">https:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n              . Unique identifier: NCT01569334.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circulationaha.117.030435","type":"journal-article","created":{"date-parts":[[2017,11,2]],"date-time":"2017-11-02T09:30:19Z","timestamp":1509615019000},"page":"1049-1059","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":31,"title":["Genetic and Functional Profiling of CD16-Dependent Natural Killer Activation Identifies Patients at Higher Risk of Cardiac Allograft Vasculopathy"],"prefix":"10.1161","volume":"137","author":[{"given":"Pascale","family":"Paul","sequence":"first","affiliation":[{"name":"Assistance Publique-H\u00f4pitaux Marseille (AP-HM), Vascular Biology and Cell Therapy Department, France (P.P., L.L., C.N.B., F.D.G., F.S.)."},{"name":"INSERM, Aix-Marseille Universit\u00e9 (AMU), VRCM, UMR-1076, France (P.P., F.D.G., F.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Picard","sequence":"additional","affiliation":[{"name":"Immunogenetic Laboratory, \u00c9tablissement Fran\u00e7ais du Sang, Marseille, France (C.P.)."},{"name":"Aix Marseille Universit\u00e9, Etablissement Fran\u00e7ais du Sang, CNRS, UMR 7268 AD\u00c9S, France (C.P., J.D.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuelle","family":"Sampol","sequence":"additional","affiliation":[{"name":"Assistance Publique-H\u00f4pitaux Marseille (AP-HM), Pharmacokinetics Department, France (E.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luc","family":"Lyonnet","sequence":"additional","affiliation":[{"name":"Assistance Publique-H\u00f4pitaux Marseille (AP-HM), Vascular Biology and Cell Therapy Department, France (P.P., L.L., C.N.B., F.D.G., F.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Di Cristofaro","sequence":"additional","affiliation":[{"name":"Assistance Publique-H\u00f4pitaux Marseille (AP-HM), Pharmacokinetics Department, France (E.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise","family":"Paul-Delvaux","sequence":"additional","affiliation":[{"name":"ENSAE-Paristech, Data Science &amp; Statistics Department, Paris, France (L.P.-D.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillaume","family":"Lano","sequence":"additional","affiliation":[{"name":"Assistance Publique-H\u00f4pitaux Marseille (AP-HM), Aix Marseille Univ, Center for Clinical Investigation, France (G.L., B.D.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corinne","family":"Nicolino-Brunet","sequence":"additional","affiliation":[{"name":"Assistance Publique-H\u00f4pitaux Marseille (AP-HM), Vascular Biology and Cell Therapy Department, France (P.P., L.L., C.N.B., F.D.G., 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