{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T20:43:47Z","timestamp":1791924227122,"version":"4.3.4"},"reference-count":40,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"9","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["CJASN"],"published-print":{"date-parts":[[2021,9]]},"abstract":"<jats:sec>\n                    <jats:title>Background and objectives<\/jats:title>\n                    <jats:p>Immune checkpoint inhibitors are increasingly used to treat various malignancies, but their application in patients with kidney transplants is complicated by high allograft rejection rates. Immune checkpoint inhibitor\u2013associated rejection is a novel, poorly understood entity demonstrating overlapping histopathologic features with immune checkpoint inhibitor\u2013associated acute interstitial nephritis, which poses a challenge for diagnosis and clinical management. We sought to improve the understanding of these entities through biopsy-based gene expression analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design, setting, participants, &amp; measurements<\/jats:title>\n                    <jats:p>NanoString was used to measure and compare the expression of 725 immune-related genes in 75 archival kidney biopsies, including a 25-sample discovery cohort comprising pure T cell\u2013mediated rejection and immune checkpoint inhibitor\u2013associated acute interstitial nephritis and an independent 50-sample validation cohort comprising immune checkpoint inhibitor\u2013associated acute interstitial nephritis, immune checkpoint inhibitor\u2013associated T cell\u2013mediated rejection, immune checkpoint inhibitor\u2013associated crescentic GN, drug-induced acute interstitial nephritis, BK virus nephropathy, and normal biopsies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Significant molecular overlap was observed between immune checkpoint inhibitor\u2013associated acute interstitial nephritis and T cell\u2013mediated rejection. Nevertheless,\n                      <jats:italic toggle=\"yes\">IFI27<\/jats:italic>\n                      , an IFN-\n                      <jats:italic toggle=\"yes\">\u03b1\u2013<\/jats:italic>\n                      induced transcript, was identified and validated as a novel biomarker for differentiating immune checkpoint inhibitor\u2013associated T cell\u2013mediated rejection from immune checkpoint inhibitor\u2013associated acute interstitial nephritis (validation cohort:\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt;0.001, area under the receiver operating characteristic curve =100%, accuracy =86%). Principal component analysis revealed heterogeneity in inflammatory gene expression patterns within sample groups; however, immune checkpoint inhibitor\u2013associated T cell\u2013mediated rejection and immune checkpoint inhibitor\u2013associated acute interstitial nephritis both demonstrated relatively more molecular overlap with drug-induced acute interstitial nephritis than T cell\u2013mediated rejection, suggesting potential dominance of hypersensitivity mechanisms in these entities.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      These results indicate that, although there is significant molecular similarity between immune checkpoint inhibitor\u2013associated rejection and acute interstitial nephritis, biopsy-based measurement of\n                      <jats:italic toggle=\"yes\">IFI27<\/jats:italic>\n                      gene expression represents a potential biomarker for differentiating these entities.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.2215\/cjn.00920121","type":"journal-article","created":{"date-parts":[[2021,7,9]],"date-time":"2021-07-09T11:05:26Z","timestamp":1625828726000},"page":"1376-1386","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":30,"title":["Gene Expression Profiling in Kidney Transplants with Immune Checkpoint Inhibitor\u2013Associated Adverse Events"],"prefix":"10.2215","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1908-1739","authenticated-orcid":false,"given":"Benjamin A.","family":"Adam","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8168-5811","authenticated-orcid":false,"given":"Naoka","family":"Murakami","sequence":"additional","affiliation":[{"name":"Renal Division, Brigham and Women\u2019s Hospital, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0881-2209","authenticated-orcid":false,"given":"Graeme","family":"Reid","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katie","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruqaya","family":"Jasim","sequence":"additional","affiliation":[{"name":"Department of 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