{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T09:28:00Z","timestamp":1786354080741,"version":"build-2736575974"},"reference-count":40,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,8,8]],"date-time":"2026-08-08T00:00:00Z","timestamp":1786147200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Department of Research and Universities of the Generalitat de Catalunya","award":["DI-2024-00051"],"award-info":[{"award-number":["DI-2024-00051"]}]},{"name":"Department of Research and Universities of the Generalitat de Catalunya","award":["DI-2024-00112"],"award-info":[{"award-number":["DI-2024-00112"]}]},{"award":["DI-2024-00051"],"award-info":[{"award-number":["DI-2024-00051"]}],"id":[{"id":"https:\/\/ror.org\/01bg62x04","id-type":"ROR","asserted-by":"publisher"}]},{"award":["DI-2024-00112"],"award-info":[{"award-number":["DI-2024-00112"]}],"id":[{"id":"https:\/\/ror.org\/01bg62x04","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Spanish Ministry of Science","award":["CPP2021-008394"],"award-info":[{"award-number":["CPP2021-008394"]}]},{"award":["CPP2021-008394"],"award-info":[{"award-number":["CPP2021-008394"]}],"id":[{"id":"https:\/\/ror.org\/023ktd084","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["CD21\/00087"],"award-info":[{"award-number":["CD21\/00087"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["23:00106"],"award-info":[{"award-number":["23:00106"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"award":["CD21\/00087"],"award-info":[{"award-number":["CD21\/00087"]}],"id":[{"id":"https:\/\/ror.org\/00ca2c886","id-type":"ROR","asserted-by":"publisher"}]},{"award":["23:00106"],"award-info":[{"award-number":["23:00106"]}],"id":[{"id":"https:\/\/ror.org\/00ca2c886","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Med. Sci.","Medical Sciences"],"abstract":"<jats:p>Background\/Objectives: Routine biomarkers and clinical scores do not directly assess functional immune responsiveness in suspected sepsis. We evaluated whether the TNF-\u03b1 Release Assay (TARA), a whole-blood LPS-induced functional assay, is associated with an early cytokine-low immune phenotype in Emergency Department (ED) patients. Methods: In this prospective single-center cohort, adults with suspected sepsis and NEWS2 \u2265 3 were sampled at presentation, at 4 h and, when available, at 24 h. Immune phenotypes were defined independently of TARA by unsupervised k-means clustering of 12 circulating cytokines at 4 h, and a continuous Low-Response Cytokine Score (LRCS) was derived, with higher values indicating lower global cytokine concentrations. Results: Among 152 patients, three phenotypes were identified: C1 cytokine-low (n = 56), C2 inflammatory\/intermediate (n = 63), and C3 IFN-\u03b3\/MCP-3\/IL-17A-high (n = 33). Indicative TARA low-response status was independently associated with a higher LRCS after adjustment for clinical covariates and procalcitonin (PCT), both at presentation (\u03b2 = 0.33; 95% CI, 0.14\u20130.53; p = 0.001) and at 4 h (\u03b2 = 0.38; 95% CI, 0.19\u20130.57; p &lt; 0.001). Indicative TARA low-response results at 4 h were most frequent in C1 and least frequent in C3 (75% vs. 45%). Exploratory clinical comparisons showed lower recorded early escalation in C1, whereas Sepsis-3 final diagnosis and in-hospital mortality were similar across phenotypes. Conclusions: A TARA low-response status was independently associated with an early circulating cytokine-low phenotype defined without reference to TARA or outcomes, providing information complementary to routine biomarkers and clinical severity scores. These exploratory findings support TARA as a complementary functional immune readout but require external validation and clinical-impact evaluation.<\/jats:p>","DOI":"10.3390\/medsci14040465","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T08:08:53Z","timestamp":1786349333000},"page":"465","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Early Identification of a Cytokine-Low Immune Phenotype in Suspected Sepsis Using a Point-of-Care Whole-Blood TNF-\u03b1 Release Assay"],"prefix":"10.3390","volume":"14","author":[{"given":"Erika P.","family":"Plata-Menchaca","sequence":"first","affiliation":[{"name":"Medicine Department, Universitat Aut\u00f2noma de Barcelona, Bellaterra, 08193 Barcelona, Spain"},{"name":"Hamad Medical Corporation, Medical Intensive Care Unit Department, Doha P.O. Box 3050, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Berta","family":"Cister\u00f3","sequence":"additional","affiliation":[{"name":"Emergency Department, Hospital Universitari Parc Taul\u00ed, Institut d\u2019Investigaci\u00f3 i Innovaci\u00f3 Parc Taul\u00ed (I3PT-CERCA), 08208 Sabadell, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9454-062X","authenticated-orcid":false,"given":"Adrian","family":"Ceccato","sequence":"additional","affiliation":[{"name":"Critical Care Center, Hospital Universitari Parc Taul\u00ed, Institut d\u2019Investigaci\u00f3 i Innovaci\u00f3 Parc Taul\u00ed (I3PT-CERCA), Department of Medicine, Universitat Aut\u00f2noma de Barcelona, 08208 Sabadell, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-1320-9536","authenticated-orcid":false,"given":"Veronica","family":"Monforte","sequence":"additional","affiliation":[{"name":"Critical Care Center, Hospital Universitari Parc Taul\u00ed, Institut d\u2019Investigaci\u00f3 i Innovaci\u00f3 Parc Taul\u00ed (I3PT-CERCA), Department of Medicine, Universitat Aut\u00f2noma de Barcelona, 08208 Sabadell, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-6456-3803","authenticated-orcid":false,"given":"Queralt","family":"Caus-Capdevila","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Pharmaceutical Technology and Physical Chemistry, University of Barcelona, 08028 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9611-1781","authenticated-orcid":false,"given":"Aina","family":"Areny-Balaguero","sequence":"additional","affiliation":[{"name":"Critical Care Center, Hospital Universitari Parc Taul\u00ed, Institut d\u2019Investigaci\u00f3 i Innovaci\u00f3 Parc Taul\u00ed (I3PT-CERCA), Department of Medicine, Universitat Aut\u00f2noma de Barcelona, 08208 Sabadell, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0658-6255","authenticated-orcid":false,"given":"Elena","family":"Campa\u00f1a-Duel","sequence":"additional","affiliation":[{"name":"Critical Care Center, Hospital Universitari Parc Taul\u00ed, Institut d\u2019Investigaci\u00f3 i Innovaci\u00f3 Parc Taul\u00ed (I3PT-CERCA), Department of Medicine, Universitat Aut\u00f2noma de Barcelona, 08208 Sabadell, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4085-5324","authenticated-orcid":false,"given":"Marta","family":"Camprub\u00ed-Rimblas","sequence":"additional","affiliation":[{"name":"Critical Care Center, Hospital Universitari Parc Taul\u00ed, Institut d\u2019Investigaci\u00f3 i Innovaci\u00f3 Parc Taul\u00ed (I3PT-CERCA), Department of Medicine, Universitat Aut\u00f2noma de Barcelona, 08208 Sabadell, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, 28029 Madrid, 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Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa","family":"Roman","sequence":"additional","affiliation":[{"name":"Loop Dx, StartUB!-University of Barcelona, 08028 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joan","family":"Vieyra","sequence":"additional","affiliation":[{"name":"Loop Dx, StartUB!-University of Barcelona, 08028 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judit","family":"Cubedo","sequence":"additional","affiliation":[{"name":"Loop Dx, StartUB!-University of Barcelona, 08028 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduard","family":"Guerrero","sequence":"additional","affiliation":[{"name":"Loop Dx, StartUB!-University of Barcelona, 08028 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emili","family":"Gen\u00e9","sequence":"additional","affiliation":[{"name":"Emergency Department, Hospital 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