{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T05:06:03Z","timestamp":1780031163164,"version":"3.53.1"},"reference-count":49,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T00:00:00Z","timestamp":1780012800000},"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>Intrathecal immunoglobulin synthesis is a hallmark of multiple sclerosis (MS) and can be assessed using the kappa free light chain (\u03ba-FLC) index. Although widely adopted, the optimal diagnostic cut-off of the \u03ba-FLC index may vary according to the clinical context and comparison group.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To evaluate the diagnostic performance of the \u03ba-FLC index for MS in a real-world series including inflammatory and non-inflammatory neurological disorders.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a retrospective cross-sectional study including consecutive patients aged \u226516 years undergoing diagnostic lumbar puncture at a tertiary public hospital in Argentina. Patients were classified as MS\/clinically isolated syndrome (MS\/CIS), other inflammatory neurological diseases (OIND), or non-inflammatory neurological diseases (NIND). \u03ba-FLC, IgG, and albumin were measured in paired cerebrospinal fluid and serum samples, and \u03ba-FLC index was calculated using quotient-based normalization. In addition, intrathecal \u03ba-FLC synthesis was assessed using the hyperbolic Reiber diagram (Reiber\u2019s diagram). Diagnostic performance was assessed using receiver operating characteristic (ROC) curves, with cut-off values derived from Youden\u2019s index and compared with previously proposed thresholds.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 124 patients were included (49 MS\/CIS, 48 OIND, 27 NIND). Median \u03ba-FLC index values were significantly higher in MS\/CIS compared with OIND and NIND (p &amp;lt; 0.001). In the primary comparison between MS\/CIS and OIND, the optimal \u03ba-FLC index cut-off was 14.6, yielding a sensitivity of 73.5% and a specificity of 68.1%. The lower threshold of 6.1 showed higher sensitivity (85.7%) but limited specificity (35.4%), while Reiber\u2019s diagram for \u03ba-FLC showed the highest sensitivity (91.8%) but lower specificity (45.8%).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The \u03ba-FLC index is a valuable quantitative biomarker of intrathecal immunoglobulin synthesis in MS. In our setting, a higher \u03ba-FLC index threshold provided a more balanced diagnostic profile, whereas Reiber\u2019s diagram favored sensitivity. Higher \u03ba-FLC index thresholds may improve diagnostic specificity in real-world clinical settings and should be validated in independent series.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1803446","type":"journal-article","created":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T04:50:59Z","timestamp":1780030259000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Kappa free light chain index in multiple sclerosis and other inflammatory CNS diseases: a pilot single-center study from Argentina"],"prefix":"10.3389","volume":"17","author":[{"given":"Analisa","family":"Manin","sequence":"first","affiliation":[{"name":"Neuroimmunology Section, Neurology Division, J. M. Ramos Mej\u00eda Hospital; University of Buenos Aires (UBA)","place":["Buenos Aires, Argentina"]},{"name":"Argentine Center for Neuroimmunological Diseases (CADENI), Faculty of Medicine, University of Buenos Aires (UBA)","place":["Buenos Aires, Argentina"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernanda","family":"Ingenito","sequence":"additional","affiliation":[{"name":"Immunology Section, Neuroimmunology Area, Carlos G. Durand General Acute Care Hospital","place":["Buenos Aires, Argentina"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evangelina Valeria","family":"Cores","sequence":"additional","affiliation":[{"name":"Research Institute, Faculty of Medicine, University of Buenos Aires","place":["Buenos Aires, Argentina"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego","family":"Alarc\u00f3n Guerrero","sequence":"additional","affiliation":[{"name":"Argentine Center for Neuroimmunological Diseases (CADENI), Faculty of Medicine, University of Buenos Aires (UBA)","place":["Buenos Aires, Argentina"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia Graciela","family":"Ramos","sequence":"additional","affiliation":[{"name":"Immunology Section, Neuroimmunology Area, Carlos G. Durand General Acute Care Hospital","place":["Buenos Aires, Argentina"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9s M.","family":"Villa","sequence":"additional","affiliation":[{"name":"Neuroimmunology Section, Neurology Division, J. M. Ramos Mej\u00eda Hospital; University of Buenos Aires (UBA)","place":["Buenos Aires, Argentina"]},{"name":"Argentine Center for Neuroimmunological Diseases (CADENI), Faculty of Medicine, University of Buenos Aires (UBA)","place":["Buenos Aires, Argentina"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1177\/13524585221134213","article-title":"Cerebrospinal fluid kappa free light chains for the diagnosis of multiple sclerosis: a systematic review and meta-analysis","volume":"29","author":"Hegen","year":"2023","journal-title":"Multiple Sclerosis J"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.15364","article-title":"Kappa free light chain index as a diagnostic biomarker in multiple sclerosis","volume":"159","author":"Rosenstein","year":"2021","journal-title":"J 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