{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T06:01:26Z","timestamp":1785391286192,"version":"3.55.0"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T00:00:00Z","timestamp":1785369600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Molecular histocompatibility assessment using eplet mismatch and Predicted Indirectly ReCognizable HLA Epitopes (PIRCHE) scores has improved immunologic risk stratification in kidney transplantation, but its clinical implementation remains limited, particularly for donor\u2013recipient pairs with medium eplet mismatch.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a single-center retrospective cohort study of 493 adult kidney transplant recipients (2021\u20132024). Eplet mismatch was categorized based on Wiebe\/Nickerson criteria, and medium mismatch pairs were further stratified using PIRCHE-T2 and PIRCHE-B scores. The primary outcome was early allograft injury within one year, defined as a composite of donor-specific antibody (DSA) development, histologic or molecular rejection, or elevation of donor-derived cell-free DNA (dd-cfDNA). Associations were assessed using Cox regression and Kaplan\u2013Meier analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Zero and low eplet mismatch groups had similar outcomes and were combined as the low-risk reference group. Compared with this group, medium eplet mismatch was associated with increased risk of early allograft injury (adjusted hazard ratio [aHR] 2.44, 95% confidence interval [CI] 1.41\u20134.23), biopsy-conditioned rejection (aHR 7.47, 95% CI 2.07\u201326.91), and elevated dd-cfDNA (aHR 4.83, 95% CI 1.70\u201313.75), while high mismatch conferred greater risk (aHR 5.17, 95% CI 2.86\u20139.33). Among medium mismatch recipients, ~20% were reclassified as medium\u2013low risk based on PIRCHE scores; this subgroup showed no statistically significant increase in risk relative to the low-risk group for early allograft injury (aHR 1.87, 95% CI 0.92\u20133.81), DSA, rejection, or dd-cfDNA, although confidence intervals were wide and a clinically meaningful increase in risk cannot be excluded.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Medium eplet mismatch recipients with low PIRCHE scores had no statistically significant increase in risk compared with the zero\/low mismatch group, although confidence intervals were wide. Molecular matching may help refine risk stratification and expand donor options, but the PIRCHE-T2\/-B thresholds\u2014derived from an overlapping cohort\u2014require external validation before clinical use.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1873261","type":"journal-article","created":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T05:40:17Z","timestamp":1785390017000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinical application of PIRCHE scores: reclassifying immunologic risk in patients with medium eplet mismatch"],"prefix":"10.3389","volume":"17","author":[{"given":"Miklos Z.","family":"Molnar","sequence":"first","affiliation":[{"name":"Transplant Institute, University of Rochester Medical Center","place":["Rochester, NY, United States"]},{"name":"Division of Nephrology, Department of Medicine, University of Rochester","place":["Rochester, NY, United States"]},{"name":"Department of Surgery, University of Rochester","place":["Rochester, NY, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kendon J.","family":"Holdaway","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Nephrology & Hypertension, Spencer Fox Eccles School of Medicine at the University of Utah","place":["Salt Lake City, UT, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Divya","family":"Raghavan","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Nephrology & Hypertension, Spencer Fox Eccles School of Medicine at the University of Utah","place":["Salt Lake City, UT, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silviana","family":"Marineci","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Nephrology & Hypertension, Spencer Fox Eccles School of Medicine at the University of Utah","place":["Salt Lake City, UT, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fruzsina","family":"Toth","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Nephrology & Hypertension, Spencer Fox Eccles School of Medicine at the University of Utah","place":["Salt Lake City, UT, United States"]},{"name":"Doctoral College, Theoretical and Translational Medicine Division, Semmelweis University","place":["Budapest, Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katalin","family":"Fornadi","sequence":"additional","affiliation":[{"name":"Department of Surgery, Division of Transplantation and Advanced Hepatobiliary Surgery, Spencer Fox Eccles School of Medicine at the University of Utah","place":["Salt Lake City, UT, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Niemann","sequence":"additional","affiliation":[{"name":"PIRCHE AG","place":["Berlin, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1056\/nejmra1802677","article-title":"Antibody-mediated rejection of solid-organ allografts","volume":"379","author":"Loupy","year":"2018","journal-title":"N Engl J Med"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.15177","article-title":"HLA-DR\/DQ molecular mismatch: a prognostic biomarker for primary alloimmunity","volume":"19","author":"Wiebe","year":"2019","journal-title":"Am J Transplant"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines11102741","article-title":"Donor-derived cell-free DNA at 1 month after kidney transplantation relates to HLA class II eplet mismatch 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