{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T00:18:31Z","timestamp":1793837911772,"version":"4.6.1"},"reference-count":47,"publisher":"Walter de Gruyter GmbH","license":[{"start":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T00:00:00Z","timestamp":1787270400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec id=\"j_cclm-2026-0944_abs_001\">\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Serum neurofilament light chain (sNfL) reflects neuroaxonal injury in relapsing-remitting multiple sclerosis (RRMS), but its clinical utility is limited by high interindividual variability and confounders such as renal function. Population-based thresholds may therefore be suboptimal for longitudinal monitoring. The reference change value (RCV), an intraindividual approach based on biological variation, remains insufficiently validated in real-world settings.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_cclm-2026-0944_abs_002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this retrospective cohort study, 967 sNfL determinations from 295 RRMS patients were analyzed (LUMIPULSE G600II). Measurements were matched to clinical relapse and MRI activity within \u00b190\u00a0days. Associations with log-sNfL were assessed using linear mixed-effects models. RCV and population-based threshold (PBT) were compared as factors associated with inflammatory activity using cluster-robust logistic regression and ROC analysis. Correlation with new MRI lesion count was also evaluated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_cclm-2026-0944_abs_003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The intraclass correlation coefficient was 0.536. RCV elevation showed a highly significant association with active MRI (OR 4.93, 95\u202f% CI 2.49\u20139.77) and clinical relapse (OR 6.48, 95\u202f% CI 2.75\u201315.25), whereas PBT elevation did not reach statistical significance for either outcome (active MRI: OR 1.52, p=0.290; clinical relapse: OR 2.38, p=0.073). Clinical relapse and MRI activity were independently associated with mean sNfL increases of +72.1\u202f% (95\u202f% CI +53.7\u202f%, +92.7\u202f%) and +24.5\u202f% (95\u202f% CI +13.7\u202f%, +36.3\u202f%), respectively. Renal impairment was a major confounder, with sNfL elevations of +16.0\u202f% in eGFR G2 and +67.8\u202f% in G3\u2013G5. Negative predictive values exceeded 91\u202f% across all markers and outcomes. sNfL correlated with new MRI lesion count (Spearman \u03c1=0.498, p&lt;0.0001), with a Youden-optimal threshold of\u00a0\u22654 lesions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_cclm-2026-0944_abs_004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>sNfL measured on the LUMIPULSE platform is a valid real-world biomarker of inflammatory activity in RRMS. Its high interindividual variability makes RCV-based intraindividual interpretation substantially more informative than population-based thresholding for longitudinal monitoring. The consistently high negative predictive value supports its use as a rule-out tool for active neuroinflammation and provides a rational basis for risk-adapted MRI surveillance in clinically stable patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1515\/cclm-2026-0944","type":"journal-article","created":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T03:56:01Z","timestamp":1787284561000},"source":"Crossref","is-referenced-by-count":2,"title":["Serum neurofilament light chain as a biomarker of inflammatory activity in relapsing-remitting multiple sclerosis: a real-world longitudinal cohort study"],"prefix":"10.1515","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2603-9651","authenticated-orcid":false,"given":"Silvia","family":"de las Heras Fl\u00f3rez","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory , Hospital Universitario Nuestra Se\u00f1ora de Candelaria , Santa Cruz de Tenerife , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0976-2653","authenticated-orcid":false,"given":"Gema","family":"Garc\u00eda de la Rosa","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory , Hospital Universitario Nuestra Se\u00f1ora de Candelaria , Santa Cruz de Tenerife , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vicente","family":"Mart\u00edn Garc\u00eda","sequence":"additional","affiliation":[{"name":"Section of Neuroradiology, Department of Radiology , Hospital Universitario Nuestra Se\u00f1ora de Candelaria , Santa Cruz de Tenerife , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel \u00c1ngel","family":"Hern\u00e1ndez P\u00e9rez","sequence":"additional","affiliation":[{"name":"Department of Neurology , Hospital Universitario Nuestra Se\u00f1ora de Candelaria , Santa Cruz de Tenerife , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula","family":"Oramas Padr\u00f3n","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory , Hospital Universitario Nuestra Se\u00f1ora de Candelaria , Santa Cruz de Tenerife , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Burruezo Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory , Hospital Universitario Nuestra Se\u00f1ora de Candelaria , Santa Cruz de Tenerife , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge","family":"Nuevo Garc\u00eda","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory , Hospital Universitario Nuestra Se\u00f1ora de Candelaria , Santa Cruz de Tenerife , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mercedes","family":"Carretero P\u00e9rez","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory , Hospital Universitario Nuestra Se\u00f1ora de Candelaria , Santa Cruz de Tenerife , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2026,8,21]]},"reference":[{"key":"2026082103555812404_j_cclm-2026-0944_ref_001","doi-asserted-by":"crossref","unstructured":"Walton, C, King, R, Rechtman, L, Kaye, W, Leray, E, Marrie, RA, et al.. 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