{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T11:24:31Z","timestamp":1786965871080,"version":"build-2736575974"},"reference-count":34,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:00:00Z","timestamp":1786924800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background\/Objectives: Ferritin and soluble interleukin-2 receptor \u03b1 (sIL-2R\u03b1) are HLH-related biomarkers, but their comparative discrimination in pediatric critical illness is uncertain. We primarily compared their discrimination for adjudicated HLH in hyperferritinemic PICU children and secondarily assessed PICU mortality. Methods: This prospective single-center study enrolled 75 children aged 1 month\u201318 years with ferritin \u2265500 ng\/mL: 25 each with HLH, sepsis\/septic shock, or other diseases. Both biomarkers were measured from the same admission sample. Research-use sIL-2R\u03b1 was reported in ng\/mL without cross-calibration to the HLH-2004 U\/mL scale; adjudicators were blinded to sIL-2R\u03b1, whereas ferritin informed the reference process. Analyses used ROC, Firth regression, targeted post hoc paired AUC tests with Holm adjustment, bootstrap optimism correction, and cross-validation. Results: For adjudicated HLH, ferritin showed greater discrimination than sIL-2R\u03b1 (AUC, 0.898 vs. 0.690; \u0394AUC, 0.208; Holm-adjusted p = 0.019). The exploratory 1614-ng\/mL ferritin cutoff had 92% sensitivity and 76% specificity. Although sIL-2R\u03b1 remained associated with HLH after ferritin adjustment (OR, 1.089 per ng\/mL; p = 0.002), adding it did not significantly improve discrimination beyond ferritin (p = 0.663). For secondary mortality, ferritin showed greater discrimination than sIL-2R\u03b1 (AUC, 0.754 vs. 0.495; Holm-adjusted p = 0.019). Adding ferritin to PRISM III increased the apparent AUC from 0.725 to 0.811, but the comparison was not statistically significant (p = 0.105); the bootstrap optimism-corrected AUC was 0.800. Conclusions: In this hyperferritinemic PICU cohort, ferritin showed greater discrimination for adjudicated HLH than the studied sIL-2R\u03b1 assay, and adding sIL-2R\u03b1 did not significantly improve discrimination. Findings should be interpreted in the context of the studied assay and reference process. The exploratory mortality model requires external validation.<\/jats:p>","DOI":"10.3390\/diagnostics16162600","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T10:04:36Z","timestamp":1786961076000},"page":"2600","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Diagnostic and Prognostic Value of Ferritin and Soluble Interleukin-2 Receptor \u03b1 in Critically Ill Children with Hyperferritinemia"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-6121-9021","authenticated-orcid":false,"given":"\u0130lknur","family":"Pen\u00e7e","sequence":"first","affiliation":[{"name":"Department of Pediatrics, G\u00f6ztepe Prof. Dr. S\u00fcleyman Yal\u00e7\u0131n City Hospital, Faculty of Medicine, Istanbul Medeniyet University, Istanbul 34722, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hazal C.","family":"Tu\u011frul","sequence":"additional","affiliation":[{"name":"Department of Pediatric Intensive Care, Health Sciences University \u00dcmraniye Training and Research Hospital, Istanbul 34764, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8411-3138","authenticated-orcid":false,"given":"Mahmud Esad","family":"Pen\u00e7e","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Faculty of Medicine, Marmara University, Istanbul 34854, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0317-5872","authenticated-orcid":false,"given":"G\u00fcrkan","family":"Atay","sequence":"additional","affiliation":[{"name":"Department of Pediatric Intensive Care, Health Sciences University \u00dcmraniye Training and Research Hospital, Istanbul 34764, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1230-7777","authenticated-orcid":false,"given":"Sibel","family":"Kura\u015f","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine, Health Sciences University, Istanbul 34668, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ceren","family":"Bilg\u00fcn","sequence":"additional","affiliation":[{"name":"Department of Pediatric Intensive Care, Health Sciences University \u00dcmraniye Training and Research Hospital, Istanbul 34764, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3393-3363","authenticated-orcid":false,"given":"Seher","family":"Erdo\u011fan","sequence":"additional","affiliation":[{"name":"Department of Pediatric Intensive Care, Health Sciences University \u00dcmraniye Training and Research Hospital, Istanbul 34764, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1007\/s13312-022-2668-1","article-title":"Serum ferritin for predicting outcome in children with severe sepsis in the pediatric intensive care unit","volume":"59","author":"Shaikh","year":"2022","journal-title":"Indian Pediatr."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"98","DOI":"10.3345\/cep.2022.00654","article-title":"Ferritin in pediatric critical illness: A scoping review","volume":"66","author":"Valerie","year":"2023","journal-title":"Clin. 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