{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T18:17:23Z","timestamp":1790360243086,"version":"4.1.0"},"reference-count":44,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T00:00:00Z","timestamp":1770681600000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["413501650"],"award-info":[{"award-number":["413501650"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["530229798"],"award-info":[{"award-number":["530229798"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SFB\/TRR 274"],"award-info":[{"award-number":["SFB\/TRR 274"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Intrathecal immunoglobulin synthesis is a hallmark of neuroinflammatory diseases. Free kappa light chains (FLCK) in cerebrospinal fluid (CSF) have emerged as a sensitive biomarker of B\u2010cell activity in the central nervous system (CNS), yet their relationship to immunoglobulin M (IgM) synthesis and polyspecific antiviral responses remains unclear. We aimed to delineate the diagnostic and immunological significance of FLCK in relation to intrathecal IgM production and the measles\u2013rubella\u2013zoster\u2013herpes (MRZH) antibody reaction across a broad neurological spectrum. We retrospectively analyzed paired CSF and serum samples from 240 patients showing evidence of intrathecal immune activity, defined by oligoclonal bands (OCB), MRZH positivity, or IgM intrathecal fraction (IF)\u2009\u2265\u200910%. Intrathecal synthesis of immunoglobulin classes and FLCK was quantified using Reiber's hyperbolic reference functions. Patients were classified into multiple sclerosis (MS), noninfectious inflammatory neurological disease (NI\u2010IND), infectious neurological disease (IND), neurodegenerative disease (NDD), tumor disease (TUM), and other neurological disease (OND). FLCK intrathecal synthesis (IF\u2009\u2265\u200910%) was detected in 81.7% of patients, including 98% of MS cases. FLCK levels were significantly higher in inflammatory and infectious diseases compared with non\u2010inflammatory conditions (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001). A subset of OCB\u2010negative but FLCK\u2010positive patients exhibited intrathecal IgM synthesis, suggesting that FLCK capture non\u2010IgG immune responses. In infectious diseases, high FLCK IF correlated with IgM synthesis, whereas in MS and autoimmune disorders, additional immunoglobulin classes likely contributed. FLCK levels also paralleled MRZH reactivity and were highest in patients with multiple viral antibody indices, particularly measles. These findings position FLCK as a quantitative and broadly applicable marker of intrathecal immunoglobulin synthesis across diverse CNS pathologies. FLCK may extend diagnostic sensitivity beyond IgG\u2010based assays and aid in the integrative evaluation of cerebrospinal fluid biomarkers. Prospective studies should evaluate their prognostic value and specificity across neuroinflammatory and infectious diseases.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc70383-gra-0001-m.png\">\n                        <jats:alt-text>image<\/jats:alt-text>\n                      <\/jats:graphic>\n                    <\/jats:boxed-text>\n                  <\/jats:p>","DOI":"10.1111\/jnc.70383","type":"journal-article","created":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T10:20:17Z","timestamp":1770718817000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Intrathecal Kappa Free Light Chains in Relation to\n                    <scp>IgM<\/scp>\n                    Synthesis and\n                    <scp>MRZH<\/scp>\n                    Reaction in a Mixed Neurological Cohort"],"prefix":"10.1111","volume":"170","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-2326-7017","authenticated-orcid":false,"given":"Kristina","family":"auf dem Brinke","sequence":"first","affiliation":[{"name":"Department of Neurology University Medical Center  G\u00f6ttingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noah Benedict","family":"Thust","sequence":"additional","affiliation":[{"name":"Department of Neurology University Medical Center  G\u00f6ttingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amina","family":"Simou","sequence":"additional","affiliation":[{"name":"Department of Neurology University Medical Center  G\u00f6ttingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seyed Siyawasch Justus","family":"Lattau","sequence":"additional","affiliation":[{"name":"Department of Neurology University Medical Center  G\u00f6ttingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Lange","sequence":"additional","affiliation":[{"name":"Department of Neurology University Medical Center  G\u00f6ttingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niels","family":"Hansen","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy University Medical Center  G\u00f6ttingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Wallbach","sequence":"additional","affiliation":[{"name":"Department of Nephrology University Medical Center  G\u00f6ttingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk","family":"Fitzner","sequence":"additional","affiliation":[{"name":"Department of Neurology University Medical Center  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