{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T15:48:33Z","timestamp":1791820113016,"version":"4.3.4"},"reference-count":128,"publisher":"Ovid Technologies (Wolters Kluwer Health)","license":[{"start":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T00:00:00Z","timestamp":1786579200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Institute of Infection and Immunity","award":["469957"],"award-info":[{"award-number":["469957"]}],"id":[{"id":"https:\/\/ror.org\/05wdecy17","id-type":"ROR","asserted-by":"crossref"}]},{"name":"University Health Network Foundation","award":["579068260776, 579067450776, 579072310776"],"award-info":[{"award-number":["579068260776, 579067450776, 579072310776"]}],"id":[{"id":"https:\/\/ror.org\/042xt5161","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Toronto General Hospital Research Institute, University Health Network","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"https:\/\/ror.org\/042xt5161","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Natural Sciences and Engineering Research Council of Canada","award":["RGPIN-2024-04314"],"award-info":[{"award-number":["RGPIN-2024-04314"]}],"id":[{"id":"https:\/\/ror.org\/01h531d29","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Canadian Institutes of Health Research","award":["519474"],"award-info":[{"award-number":["519474"]}],"id":[{"id":"https:\/\/ror.org\/01gavpb45","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Canada Foundation for Innovation","award":["225404, 30865"],"award-info":[{"award-number":["225404, 30865"]}],"id":[{"id":"https:\/\/ror.org\/000az4664","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Institute of Infection and Immunity","award":["469957"],"award-info":[{"award-number":["469957"]}],"id":[{"id":"https:\/\/ror.org\/05wdecy17","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Institute of Infection and Immunity","award":["469957"],"award-info":[{"award-number":["469957"]}],"id":[{"id":"https:\/\/ror.org\/05wdecy17","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Ontario Research Fund","award":["RDI #34876, RE010-020"],"award-info":[{"award-number":["RDI #34876, RE010-020"]}]},{"name":"Barbara Mendelsohn"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["JASN"],"abstract":"<jats:sec>\n                    <jats:title>Key Points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>\n                            DSA\n                            <jats:sup>+<\/jats:sup>\n                            kidney grafts with antibody-mediated rejection had higher glomerular and tubulointerstitial complement protein levels than those with donor-specific antibodies but no rejection.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            DSA\n                            <jats:sup>+<\/jats:sup>\n                            patients without rejection lacked accommodation but showed preserved podocyte and tubular protein expression compared with antibody-mediated rejection.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            Elevated complement and decreased mitochondrial proteins were associated with death-censored allograft loss in DSA\n                            <jats:sup>+<\/jats:sup>\n                            patients with antibody-mediated rejection.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Antibody-mediated rejection (AMR) is the main driver of late kidney allograft loss. Anti-HLA donor-specific antibodies (DSAs) are strongly associated with AMR. However, 30%\u201360% of DSA\n                      <jats:sup>+<\/jats:sup>\n                      patients do not develop AMR, raising the possibility of local tissue adaptations to DSAs.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We performed unbiased proteomic analysis on glomeruli and tubulointerstitium isolated using laser-capture microdissection from the kidney biopsies of 116 DSA\n                      <jats:sup>+<\/jats:sup>\n                      kidney transplant recipients with Banff-classified active AMR, chronic active AMR, mixed AMR, or no rejection. The Significant Latent factor Interaction Discovery and Exploration (SLIDE) machine learning algorithm was used to identify latent factors linked to graft loss among patients with AMR.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We quantified 1917 glomerular and 2758 tubulointerstitial proteins by mass spectrometry, with 127 glomerular and 389 tubulointerstitial proteins significantly differentially expressed between all 4 patient groups (one-way ANOVA\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; 0.05, Tukey false discovery rate  &lt;0.05). In glomeruli, chronic active AMR had the most differentially expressed proteins, consisting primarily of complement and basement membrane components. Tubulointerstitial terminal complement proteins were also significantly increased in chronic active AMR but did not correlate with C4d deposition. Mixed AMR contained the most differentially expressed proteins in the tubulointerstitium, which were linked to IFN\u03b3-associated immune activation, stress responses, and mitochondrial metabolism. DSA\n                      <jats:sup>+<\/jats:sup>\n                      biopsies without rejection were characterized by preservation of podocyte and tubular proteins in glomeruli and tubulointerstitium, respectively, but did not show conventional markers of accommodation. SLIDE identified 3 latent factors from the glomerular proteome and 4 from the tubulointerstitial proteome that significantly distinguished AMR patients with and without graft loss, correlated significantly with allograft injury, and improved prediction of graft loss beyond standard clinical variables in a multivariable risk model. Top proteins within the glomerular SLIDE model included complement components, while top proteins for the tubulointerstitial SLIDE model included tubular and mitochondrial proteins.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>AMR and graft loss after kidney transplantation were defined by compartment-specific disruptions in complement and mitochondrial proteins.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1681\/asn.0000001224","type":"journal-article","created":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T16:30:00Z","timestamp":1786638600000},"update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":0,"title":["Altered Complement and Tubular Mitochondrial Proteins Are Linked to Graft Loss in DSA+ Antibody\u2013Mediated Rejection"],"prefix":"10.1681","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8945-9384","authenticated-orcid":false,"given":"Kieran P.","family":"Manion","sequence":"first","affiliation":[{"name":"Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada"},{"name":"Ajmera Transplant Centre, University Health Network, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-6295-8983","authenticated-orcid":false,"given":"Maya A.","family":"Allen","sequence":"additional","affiliation":[{"name":"Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada"},{"name":"Ajmera Transplant Centre, University Health Network, Toronto, Ontario, Canada"},{"name":"Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Augusta","family":"Vincent","sequence":"additional","affiliation":[{"name":"Departments of Immunology and Computational and Systems Biology, Center for Systems Immunology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergi","family":"Clotet-Freixas","sequence":"additional","affiliation":[{"name":"Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada"},{"name":"Ajmera Transplant Centre, University Health Network, Toronto, Ontario, Canada"},{"name":"Division of Nephrology, McMaster University and St. Joseph's Healthcare, Hamilton, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1934-7472","authenticated-orcid":false,"given":"Chiara","family":"Pastrello","sequence":"additional","affiliation":[{"name":"Division of Orthopedic Surgery, Osteoarthritis Research Program, Schroeder Arthritis Institute, University Health Network, Toronto, Ontario, Canada"},{"name":"Data Science Discovery Centre for Chronic Diseases, Krembil Research Institute, University Health Network, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia","family":"Farkona","sequence":"additional","affiliation":[{"name":"Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada"},{"name":"Ajmera Transplant Centre, University Health Network, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-4561-4673","authenticated-orcid":false,"given":"Alex","family":"Boshart","sequence":"additional","affiliation":[{"name":"Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada"},{"name":"Ajmera Transplant Centre, University Health Network, Toronto, Ontario, Canada"},{"name":"Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-8043-1587","authenticated-orcid":false,"given":"Slaghaniya","family":"Neupane","sequence":"additional","affiliation":[{"name":"Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada"},{"name":"Ajmera Transplant Centre, University Health Network, Toronto, Ontario, Canada"},{"name":"Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8191-4071","authenticated-orcid":false,"given":"Hong Sang","family":"Choi","sequence":"additional","affiliation":[{"name":"Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada"},{"name":"Ajmera Transplant Centre, University Health Network, Toronto, Ontario, Canada"},{"name":"Department of Internal Medicine, Chonnam National University Medical School and Hospital, Gwangju, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stella","family":"Wang","sequence":"additional","affiliation":[{"name":"Biostatistics Department, University Health Network, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ella","family":"Huszti","sequence":"additional","affiliation":[{"name":"Biostatistics Department, University Health Network, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-0459-9018","authenticated-orcid":false,"given":"Shenghui","family":"Su","sequence":"additional","affiliation":[{"name":"Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada"},{"name":"Ajmera Transplant Centre, University Health Network, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5213-8314","authenticated-orcid":false,"given":"Jinguo","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada"},{"name":"HLA Laboratory, Laboratory Medicine Program, University Health Network, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3024-8018","authenticated-orcid":false,"given":"Jeffrey","family":"Kiernan","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada"},{"name":"HLA Laboratory, Laboratory Medicine Program, University Health Network, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9532-7221","authenticated-orcid":false,"given":"Sean","family":"Delaney","sequence":"additional","affiliation":[{"name":"Alberta Transplant Institute, University of Alberta, Edmonton, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sadia","family":"Baig","sequence":"additional","affiliation":[{"name":"Kidney Foundation of Canada, Ottawa, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Segun","family":"Famure","sequence":"additional","affiliation":[{"name":"Ajmera Transplant Centre, University Health Network, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9355-8104","authenticated-orcid":false,"given":"Yanhong","family":"Li","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5021-9831","authenticated-orcid":false,"given":"S. Joseph","family":"Kim","sequence":"additional","affiliation":[{"name":"Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada"},{"name":"Ajmera Transplant Centre, University Health Network, Toronto, Ontario, Canada"},{"name":"Division of Nephrology, Department of Medicine, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9327-1525","authenticated-orcid":false,"given":"Aniruddh","family":"Sarkar","sequence":"additional","affiliation":[{"name":"Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Igor","family":"Jurisica","sequence":"additional","affiliation":[{"name":"Division of Orthopedic Surgery, Osteoarthritis Research Program, Schroeder Arthritis Institute, University Health Network, Toronto, Ontario, Canada"},{"name":"Data Science Discovery Centre for Chronic Diseases, Krembil Research Institute, University Health Network, Toronto, Ontario, Canada"},{"name":"Departments of Medical Biophysics and Computer Science, and Faculty of Dentistry, University of Toronto, Toronto, Ontario, Canada"},{"name":"Institute of Neuroimmunology, Slovak Academy of Sciences, Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rohan","family":"John","sequence":"additional","affiliation":[{"name":"Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, 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