{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T10:01:51Z","timestamp":1791021711565,"version":"4.1.0"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T00:00:00Z","timestamp":1762473600000},"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>The kappa free light chain (\u03ba-FLC) index is a well-established biomarker in multiple sclerosis (MS). While the prognostic value of the \u03ba-FLC index has been demonstrated in early relapsing\u2013remitting MS, its prognostic value in primary progressive MS (PPMS) has not yet been investigated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this multicenter, retrospective cohort study, patients diagnosed with PPMS with diagnostic lumbar puncture and clinical follow-up of at least 12 months were recruited from nine MS centers across five countries. At baseline, age, sex, disease duration, and the number of T2 hyperintense (T2L) and contrast-enhancing T1 lesions (CEL) on MRI were determined. \u03ba-FLC was measured using nephelometry\/turbidimetry, and the \u03ba-FLC index was calculated as (CSF \u03ba-FLC\/serum \u03ba-FLC)\/albumin quotient. At follow-up, the occurrence of disability progression and the administration of disease-modifying treatment (DMT) were registered. The primary endpoint was time to disability progression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 121 PPMS patients were included with a median age of 53 years (25th\u201375th percentile: 46\u201359) and a balanced sex distribution (48.8% female). Multivariable Cox regression analysis revealed no significant association between the \u03ba-FLC index and disability progression [hazard ratio (HR) 1.0, p = 0.950]. Prior\u00a0use of DMT (HR 0.60, p = 0.023) and brain T2L &amp;gt; 9 at baseline (HR 2.22, p\u00a0=\u00a00.026) were significantly associated with disability progression. The remaining covariates, including age, sex, disease duration, and CEL, showed no significant associations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The \u03ba-FLC index does not predict disability progression in PPMS, contrasting its growing role as a prognostic biomarker in relapsing MS. This highlights phenotypic differences in MS pathophysiology and underscores the need for prognostic biomarkers in PPMS.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1658182","type":"journal-article","created":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T05:21:31Z","timestamp":1762492891000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Prognostic value of kappa free light chain index in patients with primary progressive multiple 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