{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T22:43:28Z","timestamp":1768949008824,"version":"3.49.0"},"reference-count":7,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T00:00:00Z","timestamp":1756166400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T00:00:00Z","timestamp":1756166400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Hemodialysis International"],"published-print":{"date-parts":[[2026,1]]},"abstract":"ABSTRACT<\/jats:title>\n \n Introduction<\/jats:title>\n \n Catheter\u2010related bloodstream infections (CRBSI) represent a major cause of morbidity and mortality in hemodialysis (HD) patients. Current diagnostic reliance on blood cultures leads to delays in treatment initiation, underscoring the need for rapid biomarkers. Emerging evidence suggests that CD4\n +<\/jats:sup>\n CD25\n +<\/jats:sup>\n CD39\n +<\/jats:sup>\n regulatory T cells (Tregs) may serve as indicators of immune dysregulation during CRBSI. This study aimed to: (1) evaluate CD4\n +<\/jats:sup>\n CD25\n +<\/jats:sup>\n CD39\n +<\/jats:sup>\n Tregs as diagnostic biomarkers for CRBSI in HD patients, (2) compare the reliability of dialysis bloodline cultures versus peripheral venipuncture cultures, and (3) determine optimal fever thresholds for CRBSI prediction.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n In this prospective cohort study, we enrolled 87 HD patients with suspected CRBSI (42 confirmed CRBSI, 45 non\u2010CRBSI controls). Treg frequencies were quantified using flow cytometry. Paired blood cultures were obtained simultaneously from dialysis bloodlines and peripheral veins. CRBSI was confirmed using CDC criteria (\u2265\u20093\u2010fold higher colony count or \u2265\u20092\u2010h earlier positivity in catheter\u2010derived cultures).<\/jats:p>\n <\/jats:sec>\n \n Findings<\/jats:title>\n \n CRBSI patients showed markedly elevated Treg frequencies (14.1%\u2009\u00b1\u20094.5% vs. 3.3%\u2009\u00b1\u20092.8%,\n p<\/jats:italic>\n \u2009<\u20090.001) with outstanding diagnostic accuracy (AUC 0.974, 98.3% sensitivity, 96.3% specificity). Dialysis bloodline cultures demonstrated excellent concordance with peripheral cultures (92% agreement, \u03ba\u2009=\u20090.88). Fever >\u200938.0\u00b0C strongly predicted CRBSI (OR 18.67,\n p<\/jats:italic>\n \u2009<\u20090.001; 85% specificity). The diagnostic triad of Tregs >\u200910%, CRP >\u200950\u2009mg\/L, and fever >\u200938.0\u00b0C achieved exceptional discrimination (AUC 0.93).\n <\/jats:p>\n <\/jats:sec>\n \n Discussion<\/jats:title>\n \n CD4\n +<\/jats:sup>\n CD25\n +<\/jats:sup>\n CD39\n +<\/jats:sup>\n Tregs represent a novel, high\u2010performance biomarker for CRBSI. Combined with validated dialysis line cultures and fever thresholds, they enable rapid diagnosis and early intervention, offering a practical alternative to current culture\u2010dependent approaches in hemodialysis patients.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/hdi.70021","type":"journal-article","created":{"date-parts":[[2025,8,27]],"date-time":"2025-08-27T01:30:23Z","timestamp":1756258223000},"page":"138-148","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["CD4<\/scp>\n +<\/sup>\n CD25<\/scp>\n +<\/sup>\n CD39<\/scp>\n +<\/sup>\n Regulatory T Cells as Novel Diagnostic Biomarkers for Catheter\u2010Related Bloodstream Infections in Hemodialysis Patients"],"prefix":"10.1111","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3443-6390","authenticated-orcid":false,"given":"Hesham Kamal Habeeb","family":"Keryakos","sequence":"first","affiliation":[{"name":"Department of Internal Medicine and Nephrology Faculty of Medicine, Minia University Minia Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christina Rafat","family":"Kamal","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Nephrology Faculty of Medicine, Minia University Minia Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5486-3512","authenticated-orcid":false,"given":"Aliaa Mohamed Monir","family":"Higazi","sequence":"additional","affiliation":[{"name":"Department of Clinical Pathology Faculty of Medicine, Minia University Minia Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,8,26]]},"reference":[{"issue":"9","key":"e_1_2_11_2_1","article-title":"Incidence, Risk Factors, Organism Types, and Outcomes of Catheter\u2010Related Bloodstream Infections in Hemodialysis Patients","volume":"16","author":"Bitunguramye A.","year":"2024","journal-title":"Cureus"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12882-024-03776-8"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1086\/599376"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2013.03.005"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1012191"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijid.2014.11.006"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.829210"}],"container-title":["Hemodialysis International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/hdi.70021","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/hdi.70021","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/hdi.70021","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T09:39:23Z","timestamp":1768901963000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/hdi.70021"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,26]]},"references-count":7,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1111\/hdi.70021"],"URL":"https:\/\/doi.org\/10.1111\/hdi.70021","archive":["Portico"],"relation":{},"ISSN":["1492-7535","1542-4758"],"issn-type":[{"value":"1492-7535","type":"print"},{"value":"1542-4758","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,26]]},"assertion":[{"value":"2025-07-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-11","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-26","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}