{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T04:07:48Z","timestamp":1793678868687,"version":"4.5.1"},"reference-count":37,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JASN"],"published-print":{"date-parts":[[2019,4]]},"abstract":"\n Significance Statement<\/jats:title>\n Antibody-mediated rejection (AMR) in renal allografts, which is usually caused by antibodies (Abs) directed against HLAs, is associated with a poor transplant outcome. However, evidence of AMR in the absence of anti-HLA Abs suggests the presence of non-anti\u2013HLA Abs, presumed to react with other antigens on endothelial cells. The authors describe the clinicopathologic profiles of kidney recipients who experienced acute rejection with microvascular inflammation within 3 months after transplantation in the absence of anti-HLA donor-specific Abs. Using a new endothelial cell crossmatch assay and transcriptomic and proteomic analyses, they discovered that before transplantation, these patients carried unknown anti\u2013endothelial cell Abs in their sera that specifically targeted the glomerular microvascular endothelium. An assessment of these unknown potentially deleterious Abs may provide important diagnostic tools to prevent AMR.<\/jats:p>\n <\/jats:sec>\n \n Background<\/jats:title>\n Although anti-HLA antibodies (Abs) cause most antibody-mediated rejections of renal allografts, non-anti\u2013HLA Abs have also been postulated to contribute. A better understanding of such Abs in rejection is needed.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n We conducted a nationwide study to identify kidney transplant recipients without anti-HLA donor-specific Abs who experienced acute graft dysfunction within 3 months after transplantation and showed evidence of microvascular injury, called acute microvascular rejection (AMVR). We developed a crossmatch assay to assess serum reactivity to human microvascular endothelial cells, and used a combination of transcriptomic and proteomic approaches to identify non-HLA Abs.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n We identified a highly selected cohort of 38 patients with early acute AMVR. Biopsy specimens revealed intense microvascular inflammation and the presence of vasculitis (in 60.5%), interstitial hemorrhages (31.6%), or thrombotic microangiopathy (15.8%). Serum samples collected at the time of transplant showed that previously proposed anti\u2013endothelial cell Abs\u2014angiotensin type 1 receptor (AT1R), endothelin-1 type A and natural polyreactive Abs\u2014did not increase significantly among patients with AMVR compared with a control group of stable kidney transplant recipients. However, 26% of the tested AMVR samples were positive for AT1R Abs when a threshold of 10 IU\/ml was used. The crossmatch assay identified a common IgG response that was specifically directed against constitutively expressed antigens of microvascular glomerular cells in patients with AMVR. Transcriptomic and proteomic analyses identified new targets of non-HLA Abs, with little redundancy among individuals.<\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Our findings indicate that preformed IgG Abs targeting non-HLA antigens expressed on glomerular endothelial cells are associated with early AMVR, and that\n in vitro<\/jats:italic>\n cell-based assays are needed to improve risk assessments before transplant.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1681\/asn.2018080868","type":"journal-article","created":{"date-parts":[[2019,3,8]],"date-time":"2019-03-08T21:35:18Z","timestamp":1552080918000},"page":"692-709","source":"Crossref","is-referenced-by-count":115,"title":["Early Acute Microvascular Kidney Transplant Rejection in the Absence of Anti-HLA Antibodies Is Associated with Preformed IgG Antibodies against Diverse Glomerular Endothelial Cell Antigens"],"prefix":"10.1681","volume":"30","author":[{"given":"Marianne","family":"Delville","sequence":"first","affiliation":[{"name":"French National Institute of Health and Medical Research (INSERM) Unit 1163 and"},{"name":"Department of Biotherapy, Necker Hospital, Assistance Publique-H\u00f4pitaux de Paris (AP-HP), Paris, France;"},{"name":"Paris Descartes, Sorbonne Paris Cit\u00e9 University, Paris, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baptiste","family":"Lamarth\u00e9e","sequence":"additional","affiliation":[{"name":"Nantes Universtity, Nantes, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvain","family":"Pagie","sequence":"additional","affiliation":[{"name":"Center for Research in Transplantation and Immunology, French National Institute of Health and Medical Research (INSERM) Unit\u00e9 Mixte de Recherche (UMR) 1064, Institut Hospitalo-Universitaire (IHU) Centre Europ\u00e9en des Sciences de la Transplantation et de l'Immunoth\u00e9rapie (CESTI), Laboratoire d\u2019excellence (LabEx) Immunotherapy Graft Oncology (IGO), LabEx Transplantex, Nantes, France;"},{"name":"Nantes Universtity, Nantes, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4208-317X","authenticated-orcid":false,"given":"Sarah B.","family":"See","sequence":"additional","affiliation":[{"name":"Columbia Center for Translational Immunology, Columbia University Medical Center, New York, New York;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marion","family":"Rabant","sequence":"additional","affiliation":[{"name":"Paris Descartes, Sorbonne Paris Cit\u00e9 University, Paris, France;"},{"name":"Department of Renal Pathology, Necker Hospital, Assistance Publique-H\u00f4pitaux de Paris (AP-HP), Paris, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carole","family":"Burger","sequence":"additional","affiliation":[{"name":"Paris Descartes, Sorbonne Paris Cit\u00e9 University, Paris, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1664-2879","authenticated-orcid":false,"given":"Philippe","family":"Gatault","sequence":"additional","affiliation":[{"name":"Service de N\u00e9phrologie-Hypertension, Transplantation et Dialyses, University Hospital, Tours, France;"},{"name":"Equipe d\u2019Accueil EA4245, Transplantation, Immunologie et Inflammation (T2I), University of Tours, Tours, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magali","family":"Giral","sequence":"additional","affiliation":[{"name":"Nantes University Hospital, Institut de Transplantation-Urologie-N\u00e9phrologie (ITUN), Nantes, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Thaunat","sequence":"additional","affiliation":[{"name":"Hospices Civils de Lyon, Edouard Herriot Hospital, Department of Transplantation, Nephrology and Clinical Immunology;"},{"name":"INSERM Unit 1111, Lyon, France;"},{"name":"Claude Berna Saint-Etienne University Hospital rd University (Lyon 1), Lyon, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadia","family":"Arzouk","sequence":"additional","affiliation":[{"name":"Department of Urology, Nephrology and Kidney transplantation, Piti\u00e9 Salp\u00e9tri\u00e8re Hospital, Assistance Publique-H\u00f4pitaux de Paris (AP-HP), Paris, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre","family":"Hertig","sequence":"additional","affiliation":[{"name":"Sorbonne University, Paris, France;"},{"name":"Urgences N\u00e9phrologiques et Transplantation R\u00e9nale, Assistance Publique-H\u00f4pitaux de Paris (AP-HP), Tenon Hospital, Paris, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Hazzan","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Lille University Hospital, Lille, France;"},{"name":"Lille University, Lille, France;"},{"name":"French National Institute of Health and Medical Research (INSERM) Unit\u00e9 Mixte de Recherche (UMR) 995, Lille, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Matignon","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Renal Transplantation, Groupe Hospitalier Henri-Mondor\/Albert-Chenevier, Assistance Publique-H\u00f4pitaux de Paris (AP-HP), Cr\u00e9teil, France;"},{"name":"Paris-Est-Cr\u00e9teil University (UPEC), Cr\u00e9teil, France;"},{"name":"Institut Mondor de Recherche Biom\u00e9dicale (IMRB), Equipe 21, French National Institute of Health and Medical Research (INSERM) Unit 955, Cr\u00e9teil, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Mariat","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Dialysis and Renal Transplantation, Saint-Etienne University Hospital, 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France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johnny","family":"Sayegh","sequence":"additional","affiliation":[{"name":"Angers University, Angers, France;"},{"name":"Department of Nephrology, Dialysis and Kidney Transplantation, Angers University Hospital, Angers, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre-Fran\u00e7ois","family":"Westeel","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Dialysis and Transplantation, University Hospital, Amiens, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cyril","family":"Garrouste","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Clermont-Ferrand University Hospital, Clermont-Ferrand, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Ladri\u00e8re","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Kidney Transplantation, Nancy University Hospital, Nancy, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Vuiblet","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Renal Transplantation, Reims University Hospital, Reims, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Rivalan","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Pontchaillou University Hospital, Rennes, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Merville","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Transplantation, Dialysis and Apheresis, Pellegrin University Hospital, Bordeaux, France;"},{"name":"Centre National de la Recherche Scientifique-Unit\u00e9 Mixte de Recherche (CNRS-UMR) 5164 Immuno ConcEpT, , Bordeaux, France;"},{"name":"Bordeaux University, Bordeaux, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominique","family":"Bertrand","sequence":"additional","affiliation":[{"name":"Nephrology, Dialysis and Kidney Transplantation, Rouen University Hospital, Rouen, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alain","family":"Le Moine","sequence":"additional","affiliation":[{"name":"Erasme Hospital, Nephrology Dialysis and Transplantation Department, Bruxelles, Belgium;"},{"name":"Universit\u00e9 Libre de Bruxelles, Brussels, Belgium;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean Paul Duong","family":"Van Huyen","sequence":"additional","affiliation":[{"name":"Paris Descartes, Sorbonne Paris Cit\u00e9 University, Paris, France;"},{"name":"Department of Renal Pathology, Necker Hospital, Assistance Publique-H\u00f4pitaux de Paris (AP-HP), Paris, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Cesbron","sequence":"additional","affiliation":[{"name":"HLA Laboratory, Etablissement Fran\u00e7ais du Sang (EFS) Centre Pays de la Loire, Nantes, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Cagnard","sequence":"additional","affiliation":[{"name":"Paris Descartes, Sorbonne Paris Cit\u00e9 University, Paris, France;"},{"name":"Bioinformatics, Structure F\u00e9d\u00e9rative de Recherche Necker, French National Institute of Health and Medical Research (INSERM) US24\/ Centre National de la Recherche Scientifique (CNRS) UMS3633, Paris, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Alibeu","sequence":"additional","affiliation":[{"name":"Paris Descartes, Sorbonne Paris Cit\u00e9 University, Paris, France;"},{"name":"Genomics Core Facility, Institut Imagine-Structure F\u00e9d\u00e9rative de Recherche Necker, French National Institute of Health and Medical Research (INSERM) Unit 1163 and INSERM US24\/ Centre National de la Recherche Scientifique (CNRS) UMS3633, Paris, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon C.","family":"Satchell","sequence":"additional","affiliation":[{"name":"Bristol Renal, Bristol Heart Institute, Translational Health Sciences, Bristol Medical School, University of Bristol, Great Britain;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Legendre","sequence":"additional","affiliation":[{"name":"Paris Descartes, Sorbonne Paris Cit\u00e9 University, Paris, France;"},{"name":"Necker-Enfants Malades Institute, French National Institute of Health and Medical Research (INSERM) Unit 1151, Paris, France;"},{"name":"Department of Nephrology and Kidney Transplantation, RTRS Centaure; LabEx Transplantex, Necker Hospital, Assistance Publique-H\u00f4pitaux de Paris (AP-HP), Paris, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel","family":"Zorn","sequence":"additional","affiliation":[{"name":"Columbia Center for Translational Immunology, Columbia University Medical Center, New York, New York;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Luc","family":"Taupin","sequence":"additional","affiliation":[{"name":"Immunology and Histocompatibility Laboratory, Saint-Louis Hospital, Assistance Publique-H\u00f4pitaux de Paris (AP-HP), Paris, France;"},{"name":"French National Institute of Health and Medical Research (INSERM) Unit 1160, LabEx Transplantex, Paris France; and"},{"name":"University Paris Diderot, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B\u00e9atrice","family":"Charreau","sequence":"additional","affiliation":[{"name":"Center for Research in Transplantation and Immunology, French National Institute of Health and Medical Research (INSERM) Unit\u00e9 Mixte de Recherche (UMR) 1064, Institut Hospitalo-Universitaire (IHU) Centre Europ\u00e9en des Sciences de la Transplantation et de l'Immunoth\u00e9rapie (CESTI), Laboratoire d\u2019excellence (LabEx) Immunotherapy Graft Oncology (IGO), LabEx Transplantex, Nantes, France;"},{"name":"Nantes Universtity, Nantes, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5793-6174","authenticated-orcid":false,"given":"Dany","family":"Anglicheau","sequence":"additional","affiliation":[{"name":"Paris Descartes, Sorbonne Paris Cit\u00e9 University, Paris, France;"},{"name":"Necker-Enfants Malades Institute, French National Institute of Health and Medical Research (INSERM) Unit 1151, Paris, France;"},{"name":"Department of Nephrology and Kidney Transplantation, RTRS Centaure; LabEx Transplantex, Necker Hospital, Assistance Publique-H\u00f4pitaux de Paris (AP-HP), Paris, 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