{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T13:09:53Z","timestamp":1789477793740,"version":"build-2803163510"},"reference-count":33,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T00:00:00Z","timestamp":1786406400000},"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>Complement activation is increasingly recognized as a key driver in various critical diseases and a potential therapeutic target. However, conventional enzyme-linked immunosorbent assays (ELISAs) for complement protein detection are laboratory-bound and unsuitable for rapid clinical decision-making in the emergency and intensive care unit setting. We evaluated the feasibility of a point-of-care (POC) multiplex micro-ELISA for complement component C3, activation marker C3d and the soluble terminal complement complex (TCC) in a heterogeneous intensive care unit (ICU) population.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>Thirty-eight critically ill and three cardiopulmonary bypass patients were prospectively enrolled. Fifteen age- and sex-matched healthy volunteers served as controls. Plasma samples collected at ICU admission and days 2\u20134 were analyzed using a novel POC multiplex micro-ELISA platform and compared with established in-house and commercial ELISAs using Spearman rank correlation and receiver operating characteristic (ROC) analysis. Additional complement activation markers (C3bc, C3bBbP, C1s\/C1-INH, MASP-1\/C1-INH and C4d) were assessed to explore specific pathway involvement.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      TCC levels were significantly elevated in patients (median 3575, IQR 2048\u20136504 mAU\/ml) compared with controls (median 1286, IQR 1032\u20131903 mAU\/ml;\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&amp;lt;\u00a00.0001) at both sampling time points. The POC assay demonstrated strong rank correlation with the in-house TCC ELISA (r = 0.83,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&amp;lt;\u00a00.001) and the commercial Hycult TCC ELISA (r = 0.88,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&amp;lt;\u00a00.001). The POC TCC assay accurately discriminated patient samples above and below the ELISA-defined threshold (AUC 0.97,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&amp;lt;\u00a00.001). In contrast, C3 and C3d showed limited patient-control discriminatory ability and poor POC\u2013ELISA agreement. C3bc and C3bBbP were elevated in patients, suggesting alternative pathway amplification. C1s\/C1-INH and C4d were not significantly elevated, whereas MASP-1-C1-INH complexes were decreased in patients compared to healthy controls.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Point-of-care TCC quantification is feasible, correlates well with established ELISAs and accurately identifies elevated TCC levels in critically ill patients. Although formal method-comparison analyses were not possible to establish, TCC emerged as the most robust marker of complement activation in this ICU cohort using the evaluated POC prototype. POC testing may facilitate timely identification of complement activation in acute care settings and support integration of complement-directed diagnostics and therapeutics into clinical workflows.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1860988","type":"journal-article","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T05:40:52Z","timestamp":1786426852000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Point-of-care assessment of complement activation in the ICU: a feasibility study of rapid terminal complement complex detection in critical illness"],"prefix":"10.3389","volume":"17","author":[{"given":"Tam","family":"Cung","sequence":"first","affiliation":[{"name":"Department of Immunology, Oslo University Hospital and University of Oslo","place":["Oslo, Norway"]},{"name":"Department of Research and Development, Division of Emergencies and Critical Care, Oslo University 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Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camilla","family":"Schjalm","sequence":"additional","affiliation":[{"name":"Department of Immunology, Oslo University Hospital and University of Oslo","place":["Oslo, Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bettina","family":"M\u00fclleder","sequence":"additional","affiliation":[{"name":"GENSPEED Biotech GmbH","place":["Rainbach im M\u00fchlkreis, Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Loek","family":"Willems","sequence":"additional","affiliation":[{"name":"Research and Development Department, Hycult Biotechnology","place":["Uden, Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Max","family":"Sonnleitner","sequence":"additional","affiliation":[{"name":"GENSPEED Biotech GmbH","place":["Rainbach im M\u00fchlkreis, Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik J.M.","family":"Toonen","sequence":"additional","affiliation":[{"name":"Research and Development Department, Hycult Biotechnology","place":["Uden, Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom Eirik","family":"Mollnes","sequence":"additional","affiliation":[{"name":"Department of Immunology, Oslo University Hospital and University of Oslo","place":["Oslo, Norway"]},{"name":"Institute of Clinical Medicine, Faculty of Medicine, University of Oslo","place":["Oslo, Norway"]},{"name":"Research Laboratory, Nordland Hospital Trust","place":["Bod\u00f8, Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Barratt-Due","sequence":"additional","affiliation":[{"name":"Department of Immunology, Oslo University Hospital and University of Oslo","place":["Oslo, Norway"]},{"name":"Department of Research and Development, Division of Emergencies and Critical Care, Oslo University Hospital","place":["Oslo, 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