{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T17:10:33Z","timestamp":1788887433241,"version":"build-2803163510"},"reference-count":28,"publisher":"Walter de Gruyter GmbH","issue":"1","license":[{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,23]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec id=\"j_med-2026-1516_abs_001\">\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Renal allograft rejection diagnosis requires invasive biopsy. We assessed whether peripheral blood mRNA of 14 Hippo, interferon (IFN) and NF-\u03baB pathway genes and 11 serum biomarkers could distinguish acute rejection from stable graft function.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_med-2026-1516_abs_002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Three groups: biopsy-confirmed acute rejection (n=20), stable graft (n=25), healthy controls (n=30). PBMC mRNA was quantified by qRT-PCR; serum biomarkers by ELISA and spectrophotometry. Statistical analyses used Mann\u2013Whitney\n                      <jats:italic>U<\/jats:italic>\n                      with Benjamini\u2013Hochberg correction; ROC analyses used bootstrap 95\u202f% CIs and 5-fold cross-validation. GEO datasets GSE51675 and GSE145408 provided directional cross-validation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_med-2026-1516_abs_003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Thirteen of 14 genes were upregulated in rejection vs. controls (pFDR&lt;0.01);\n                      <jats:italic>TEAD1<\/jats:italic>\n                      (log\n                      <jats:sub>2<\/jats:sub>\n                      FC=+2.44) and\n                      <jats:italic>TRAF6<\/jats:italic>\n                      (+2.40) led.\n                      <jats:italic>ISG15<\/jats:italic>\n                      was downregulated in both transplant groups, consistent with calcineurin inhibitor-mediated suppression, while serum free ISG15 protein was unchanged in stable graft but markedly lower in rejection than in both controls and stable graft (pFDR&lt;0.001 and 0.002), discriminating rejection from stable graft in a way the mRNA signal did not. Only\n                      <jats:italic>TEAD1<\/jats:italic>\n                      (Cohen\u2019s\n                      <jats:italic>d<\/jats:italic>\n                      =1.40) and\n                      <jats:italic>YAP1<\/jats:italic>\n                      (\n                      <jats:italic>d<\/jats:italic>\n                      =1.17) discriminated rejection from stable graft with adequate power.\n                      <jats:italic>TEAD1<\/jats:italic>\n                      mRNA (AUC=0.849) and serum leptin (AUC=0.922) were the strongest single markers; their combination yielded cross-validated AUC=0.990.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_med-2026-1516_abs_004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      PBMC\n                      <jats:italic>YAP1\/TEAD1<\/jats:italic>\n                      with serum leptin are promising non-invasive biomarkers for acute renal rejection.\n                      <jats:italic>ISG15<\/jats:italic>\n                      downregulation is more consistent with calcineurin inhibitor-mediated suppression than with generalized immune impairment, although this interpretation requires direct mechanistic confirmation; notably, serum free ISG15 protein discriminated rejection from stable graft even though PBMC ISG15 mRNA did not, suggesting the protein-level measurement warrants further evaluation as a candidate marker. Prospective multicentre validation is required.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1515\/med-2026-1516","type":"journal-article","created":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T16:56:46Z","timestamp":1788886606000},"source":"Crossref","is-referenced-by-count":0,"title":["Coordinated Hippo, IFN and NF-\u03baB pathway activation in kidney rejection"],"prefix":"10.1515","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7065-8161","authenticated-orcid":false,"given":"Eda","family":"Balkan","sequence":"first","affiliation":[{"name":"Department of Medical Biology , Tissue Typing and Transplant Immunology Laboratory, Faculty of Medicine, Atat\u00fcrk University , Erzurum , T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7674-4223","authenticated-orcid":false,"given":"Murat","family":"K\u0131z\u0131lkaya","sequence":"additional","affiliation":[{"name":"Department of Medical Biology , Faculty of Medicine, A\u011fr\u0131 \u0130brahim \u00c7e\u00e7en University , A\u011fr\u0131 , T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0200-4577","authenticated-orcid":false,"given":"Mahmut","family":"Akt\u00fcrk","sequence":"additional","affiliation":[{"name":"Department of Medical Biology , Tissue Typing and Transplant Immunology Laboratory, Faculty of Medicine, Atat\u00fcrk University , Erzurum , T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6660-3870","authenticated-orcid":false,"given":"Elif","family":"Demirci","sequence":"additional","affiliation":[{"name":"Department of Pathology , Faculty of Medicine, Atat\u00fcrk University , Erzurum , T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5165-638X","authenticated-orcid":false,"given":"Necip","family":"Altunda\u015f","sequence":"additional","affiliation":[{"name":"Department of General Surgery , Faculty of Medicine, Atat\u00fcrk University , Erzurum , T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2026,9,8]]},"reference":[{"key":"2026090816564269331_j_med-2026-1516_ref_001","doi-asserted-by":"crossref","unstructured":"Naesens, M, Loupy, A, Hilbrands, L, Oberbauer, R, Bellini, MI, Glotz, D, et al.. 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