{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T19:50:54Z","timestamp":1792698654924,"version":"4.5.0"},"reference-count":51,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","funder":[{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR-16-CE17-0007-01"],"award-info":[{"award-number":["ANR-16-CE17-0007-01"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002915","name":"Fondation pour la Recherche M\u00e9dicale","doi-asserted-by":"publisher","award":["PME20180639518"],"award-info":[{"award-number":["PME20180639518"]}],"id":[{"id":"10.13039\/501100002915","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["JASN"],"published-print":{"date-parts":[[2021,2]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Binding of donor-specific antibodies (DSAs) to kidney allograft endothelial cells that does not activate the classic complement cascade can trigger the recruitment of innate immune effectors, including NK cells. Activated NK cells contribute to microvascular inflammation leading to chronic antibody-mediated rejection (AMR). Recipient NK cells can also trigger antibody-independent microvascular inflammation by sensing the absence of self HLA class I molecules (\u201cmissing self\u201d) on allograft endothelial cells. This translational study investigated whether the condition of missing self amplifies DSA-dependent NK cell activation to worsen chronic AMR.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and Results<\/jats:title>\n                    <jats:p>\n                      Among 1682 kidney transplant recipients who underwent an allograft biopsy at Lyon University Hospital between 2004 and 2017, 135 fulfilled the diagnostic criteria for AMR and were enrolled in the study. Patients with complement-fixing DSAs identified by a positive C3d binding assay (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      =73, 54%) had a higher risk of transplant failure (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.002). Among the remaining patients with complement-independent chronic AMR (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      =62, 46%), those in whom missing self was identified through donor and recipient genotyping exhibited worse allograft survival (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.02). In multivariable analysis, only proteinuria (HR: 7.24;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.01) and the presence of missing self (HR: 3.57;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.04) were independent predictors for transplant failure following diagnosis of chronic AMR. Cocultures of human NK cells and endothelial cells confirmed that addition of missing self to DSA-induced NK cell activation increased endothelial damage.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The assessment of missing self at the time of diagnosis of chronic AMR identifies patients at higher risk for kidney transplant failure.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1681\/asn.2020040433","type":"journal-article","created":{"date-parts":[[2020,11,25]],"date-time":"2020-11-25T21:35:21Z","timestamp":1606340121000},"page":"479-494","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":97,"title":["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"],"prefix":"10.1681","volume":"32","author":[{"given":"Alice","family":"Koenig","sequence":"first","affiliation":[{"name":"International Center of Infectiology research (CIRI), French Institute of Health and Medical Research (INSERM) Unit 1111, Claude Bernard University Lyon I, National Center for Scientific Research (CNRS) Mixed University Unit (UMR) 5308, Ecole Normale Sup\u00e9rieure de Lyon, University of Lyon, Lyon, France"},{"name":"Department of Transplantation, Nephrology and Clinical Immunology, Hospices Civils de Lyon, Edouard Herriot Hospital, Lyon, France"},{"name":"Lyon-Est Medical Faculty, Claude Bernard University (Lyon 1), Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Mezaache","sequence":"additional","affiliation":[{"name":"Department of Transplantation, Nephrology and Clinical Immunology, Hospices Civils de Lyon, Edouard Herriot Hospital, Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasper","family":"Callemeyn","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Transplantation, Catholic University (KU) Leuven, University of Leuven, Leuven, Belgium"},{"name":"Department of Nephrology and Renal Transplantation, University Hospitals Leuven, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Barba","sequence":"additional","affiliation":[{"name":"International Center of Infectiology research (CIRI), French Institute of Health and Medical Research (INSERM) Unit 1111, Claude Bernard University Lyon I, National Center for Scientific Research (CNRS) Mixed University Unit (UMR) 5308, Ecole Normale Sup\u00e9rieure de Lyon, University of Lyon, Lyon, France"},{"name":"Department of Transplantation, Nephrology and Clinical Immunology, Hospices Civils de Lyon, Edouard Herriot Hospital, Lyon, France"},{"name":"Lyon-Est Medical Faculty, Claude Bernard University (Lyon 1), Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virginie","family":"Mathias","sequence":"additional","affiliation":[{"name":"International Center of Infectiology research (CIRI), French Institute of Health and Medical Research (INSERM) Unit 1111, Claude Bernard University Lyon I, National Center for Scientific Research (CNRS) Mixed University Unit (UMR) 5308, Ecole Normale Sup\u00e9rieure de Lyon, University of Lyon, Lyon, France"},{"name":"Human Leukocyte Antigen (HLA) Laboratory, French National Blood Service (EFS), D\u00e9cines-Charpieu, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antoine","family":"Sicard","sequence":"additional","affiliation":[{"name":"International Center of Infectiology research (CIRI), French Institute of Health and Medical Research (INSERM) Unit 1111, Claude Bernard University Lyon I, National Center for Scientific Research (CNRS) Mixed University Unit (UMR) 5308, Ecole Normale Sup\u00e9rieure de Lyon, University of Lyon, Lyon, France"},{"name":"Department of Transplantation, Nephrology and Clinical Immunology, Hospices Civils de Lyon, Edouard Herriot Hospital, Lyon, France"},{"name":"Lyon-Est Medical Faculty, Claude Bernard University (Lyon 1), Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B\u00e9atrice","family":"Charreau","sequence":"additional","affiliation":[{"name":"Centre de Recherche en Transplantation et Immunologie (CRTI), University Hospital Center (CHU) Nantes, Universit\u00e9 de Nantes, National Institute for Health and Medical Research (INSERM), Mixed University Unit (UMR) 1064, Transplantation Urology Nephrology Institute (ITUN), Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maud","family":"Rabeyrin","sequence":"additional","affiliation":[{"name":"Department of Pathology, Hospices Civils de Lyon, Bron, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fr\u00e9d\u00e9rique","family":"Dijoud","sequence":"additional","affiliation":[{"name":"Department of Pathology, Hospices Civils de Lyon, Bron, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9cile","family":"Picard","sequence":"additional","affiliation":[{"name":"Department of Pathology, Hospices Civils de Lyon, Bron, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vannary","family":"Meas-Yedid","sequence":"additional","affiliation":[{"name":"BioImage Analysis Unit, Pasteur Institute, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Christophe","family":"Olivo-Marin","sequence":"additional","affiliation":[{"name":"BioImage Analysis Unit, Pasteur Institute, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel","family":"Morelon","sequence":"additional","affiliation":[{"name":"International Center of Infectiology research (CIRI), French Institute of Health and Medical Research (INSERM) Unit 1111, Claude Bernard University Lyon I, National Center for Scientific Research (CNRS) Mixed University Unit (UMR) 5308, Ecole Normale Sup\u00e9rieure de Lyon, University of Lyon, Lyon, France"},{"name":"Department of Transplantation, Nephrology and Clinical Immunology, Hospices Civils de Lyon, Edouard Herriot Hospital, Lyon, France"},{"name":"Lyon-Est Medical Faculty, Claude Bernard University (Lyon 1), Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5625-0792","authenticated-orcid":false,"given":"Maarten","family":"Naesens","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Transplantation, Catholic University (KU) Leuven, University of Leuven, Leuven, Belgium"},{"name":"Department of Nephrology and Renal Transplantation, University Hospitals Leuven, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Val\u00e9rie","family":"Dubois","sequence":"additional","affiliation":[{"name":"International Center of Infectiology research (CIRI), French Institute of Health and Medical Research (INSERM) Unit 1111, Claude Bernard University Lyon I, National Center for Scientific Research (CNRS) Mixed University Unit (UMR) 5308, Ecole Normale Sup\u00e9rieure de Lyon, University of Lyon, Lyon, France"},{"name":"Human Leukocyte Antigen (HLA) Laboratory, French National Blood Service (EFS), D\u00e9cines-Charpieu, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Thaunat","sequence":"additional","affiliation":[{"name":"International Center of Infectiology research (CIRI), French Institute of Health and Medical Research (INSERM) Unit 1111, Claude Bernard University Lyon I, National Center for Scientific Research (CNRS) Mixed University Unit (UMR) 5308, Ecole Normale Sup\u00e9rieure de Lyon, 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