{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T21:46:25Z","timestamp":1792014385680,"version":"4.4.0"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T00:00:00Z","timestamp":1768521600000},"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>Aim<\/jats:title>\n                    <jats:p>\n                      Kidney transplantation remains the most effective treatment for end-stage kidney disease. Still, the development of\n                      <jats:italic>de novo<\/jats:italic>\n                      donor-specific antibodies (dnDSA) increases the risk of rejection and allograft failure. While molecular matching algorithms assess B-cell and T-cell epitope mismatches, no single method fully captures rejection risk across immune pathways. This study combines the HLA Epitope Registry (Epregistry), PIRCHE-T2, and PIRCHE-B scores to enhance risk stratification, allowing for early intervention in high-risk recipients and improving long-term outcomes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A retrospective study of 594 kidney transplant recipients in Saskatchewan (1981\u20132021), Canada, was conducted, tracking\n                      <jats:italic>de novo<\/jats:italic>\n                      donor-specific antibodies (dnDSA) development until January 2024. Epitope mismatch scores were calculated using Epregistry, PIRCHE-T2, and PIRCHE-B, and receiver operating characteristic (ROC) curve analysis determined the optimal cutoff values for predicting dnDSA formation. Patients were categorized into high-risk (all scores &amp;gt; cutoff), intermediate-risk (one algorithm &amp;gt; cutoff), and low-risk (all scores &amp;lt; cutoff) groups. Kaplan-Meier survival analysis evaluated dnDSA-free survival across risk categories.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among 594 recipients, 104 individuals (17.5%) developed\n                      <jats:italic>de novo<\/jats:italic>\n                      DSA; of these, 29 patients developed more than one, resulting in a total of 146 dnDSA events. The most frequently targeted locus was HLA-DQ (72\/146, 49.3%), followed by HLA-DR (25\/146, 17.1%) and HLA-A (24\/146, 16.4%). The optimal cutoff values for predicting dnDSA were 22.5 (Epregistry), 30.5 (PIRCHE-T2), and 5.5 (PIRCHE-B) for Class I, and 15.5 (Epregistry), 17.5 (PIRCHE-T2), and 5.5 (PIRCHE-B) for Class II (all p &amp;lt; 0.05). Across all molecular mismatch load metrics, Kaplan\u2013Meier analysis demonstrated significantly lower dnDSA-free and antibody-mediated rejection (ABMR)-free survival among high-risk recipients compared with low-risk recipients (log-rank p &amp;lt; 0.001). In addition, both the PIRCHE-T2 score at HLA Class I loci and the overall PIRCHE-T2 score were significantly associated with T-cell mediated rejection (TCMR) (p &amp;lt; 0.01).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Integrating Epregistry, PIRCHE-T2, and PIRCHE-B enhances risk stratification for kidney transplant recipients. Epregistry and PIRCHE-B evaluate HLA antibody epitope mismatches, and PIRCHE-T2 focuses on T-cell mismatches. Applied in conjunction, the methods show improved predictive accuracy, making this multi-algorithm approach more effective in identifying high-risk patients. By enabling earlier interventions and personalized immunosuppressive strategies, this model has the potential to improve long-term transplant success.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1718506","type":"journal-article","created":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T05:23:07Z","timestamp":1768540987000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["An integrative algorithm combining HLA epitope registry, PIRCHE-T2, and PIRCHE-B outcomes to improve immunological risk stratification in kidney transplantation"],"prefix":"10.3389","volume":"16","author":[{"given":"He","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Beijing Anzhen Hospital Affiliated to Capital Medical University","place":["Beijing, China"]},{"name":"Histocompatibility and Immunogenetics Laboratory, St. Paul\u2019s Hospital","place":["Saskatoon, SK, Canada"]},{"name":"College of Graduate and Postdoctoral Studies, University of Saskatchewan","place":["Saskatoon, SK, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pramath","family":"Kakodkar","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of Saskatchewan","place":["Saskatoon, SK, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Medicine, University of Saskatchewan","place":["Saskatoon, SK, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of Saskatchewan","place":["Saskatoon, SK, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Niemann","sequence":"additional","affiliation":[{"name":"PIRCHE AG, Research and Development","place":["Berlin, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Destinie","family":"Webster","sequence":"additional","affiliation":[{"name":"Histocompatibility and Immunogenetics Laboratory, St. Paul\u2019s Hospital","place":["Saskatoon, SK, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Twyla","family":"Pearce","sequence":"additional","affiliation":[{"name":"Histocompatibility and Immunogenetics Laboratory, St. Paul\u2019s Hospital","place":["Saskatoon, SK, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"Shoker","sequence":"additional","affiliation":[{"name":"Saskatchewan Transplant Program, Saskatchewan Health Authority","place":["Saskatoon, SK, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Keown","sequence":"additional","affiliation":[{"name":"Vancouver Coastal Health, University of British Columbia","place":["Vancouver, BC, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Sherwood","sequence":"additional","affiliation":[{"name":"Vancouver Coastal Health, University of British Columbia","place":["Vancouver, BC, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of Saskatchewan","place":["Saskatoon, SK, Canada"]},{"name":"Department of Pathology, Brigham and Women\u2019s Hospital","place":["Boston, MA, United States"]},{"name":"Harvard Medical School","place":["Boston, MA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cody","family":"Lewis","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of Saskatchewan","place":["Saskatoon, SK, 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