Estelle Moschetti, Mélany Venet, Lise Thibaudin, Amelie Moreau, Philippe Gonzalo, Jean-Philippe Camdessanche, Yannick Tholance
{"title":"KFLC与CSF总蛋白比值可替代KFLC指数诊断多发性硬化症：814例回顾性研究","authors":"Estelle Moschetti, Mélany Venet, Lise Thibaudin, Amelie Moreau, Philippe Gonzalo, Jean-Philippe Camdessanche, Yannick Tholance","doi":"10.1212/NXI.0000000000200451","DOIUrl":null,"url":null,"abstract":"<p><strong>Background and objectives: </strong>Biological analyses are crucial for diagnosing multiple sclerosis (MS), notably detection of oligoclonal bands (OCBs) of immunoglobulin G in CSF. Kappa free light chain (KFLC) quantification in serum and CSF has recently been proposed as an additional test. In a rational medicoeconomic approach, identifying algorithms or biomarkers is important. The objective of this study was, therefore, to evaluate the correlation between CSF kappa free light chain (KFLC<sub>CSF</sub>)/total CSF protein ratio (KFLC<sub>CSF</sub>/Prot<sub>CSF</sub>) and OCB status and its performance in diagnosing MS.</p><p><strong>Methods: </strong>KFLC measurements were performed prospectively with each OCB analysis, and the data were interpreted retrospectively. A total of 814 clinical cases were included: 153 with MS or clinically isolated syndrome (CIS), 181 with other inflammatory neurologic diseases, and 480 with noninflammatory neurologic diseases. Performances of KFLC<sub>CSF</sub>/Prot<sub>CSF</sub> in predicting OCB status, diagnosing MS, and estimating evolution of CIS to MS were evaluated and compared with those of other KFLC parameters, i.e., KFLC index, and with OCB and IgG parameters.</p><p><strong>Results: </strong>KFLC<sub>CSF</sub>/Prot<sub>CSF</sub> and KFLC index performed similarly in predicting OCB status, with a sensitivity of 80.2% and a specificity of 93.4% at a threshold >0.21% for KFLC<sub>CSF</sub>/Prot<sub>CSF</sub> (area under the curve: 0.93). The percentage of agreement between OCB status and KFLC<sub>CSF</sub>/Prot<sub>CSF</sub> was 91.2%. Using KFLC<sub>CSF</sub> and KFLC<sub>CSF</sub>/Prot<sub>CSF</sub> initially could reduce OCB testing by 68% and quantitative tests by 48.4%. For diagnosing MS/CIS, KFLC<sub>CSF</sub>/Prot<sub>CSF</sub> performed similar to or slightly worse than the KFLC index but always outperformed IgG, OCB, and KFLC<sub>CSF</sub>. For this indication, the optimal threshold for KFLC<sub>CSF</sub>/Prot<sub>CSF</sub> was >0.24%. It is important to note that KFLC<sub>CSF</sub>/Prot<sub>CSF</sub> was the most predictive parameter for CIS progression to MS.</p><p><strong>Discussion: </strong>To conclude, KFLC<sub>CSF</sub>/Prot<sub>CSF</sub> is as an easier and cost-effective alternative for predicting OCB status and CIS progression to MS and assisting in the diagnosis of MS.</p><p><strong>Classification of evidence: </strong>This study provides Class II evidence that the KFLC<sub>CSF</sub>/Protein<sub>CSF</sub> ratio accurately distinguishes patients with CSF OCBs from those without CSF OCBs and patients with MS from those with other neurologic disorders.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 5","pages":"e200451"},"PeriodicalIF":7.5000,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12285672/pdf/","citationCount":"0","resultStr":"{\"title\":\"KFLC to Total CSF Protein Ratio Is an Alternative to KFLC Index to Diagnose Multiple Sclerosis: A Retrospective Study of 814 Cases.\",\"authors\":\"Estelle Moschetti, Mélany Venet, Lise Thibaudin, Amelie Moreau, Philippe Gonzalo, Jean-Philippe Camdessanche, Yannick Tholance\",\"doi\":\"10.1212/NXI.0000000000200451\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background and objectives: </strong>Biological analyses are crucial for diagnosing multiple sclerosis (MS), notably detection of oligoclonal bands (OCBs) of immunoglobulin G in CSF. Kappa free light chain (KFLC) quantification in serum and CSF has recently been proposed as an additional test. In a rational medicoeconomic approach, identifying algorithms or biomarkers is important. The objective of this study was, therefore, to evaluate the correlation between CSF kappa free light chain (KFLC<sub>CSF</sub>)/total CSF protein ratio (KFLC<sub>CSF</sub>/Prot<sub>CSF</sub>) and OCB status and its performance in diagnosing MS.</p><p><strong>Methods: </strong>KFLC measurements were performed prospectively with each OCB analysis, and the data were interpreted retrospectively. A total of 814 clinical cases were included: 153 with MS or clinically isolated syndrome (CIS), 181 with other inflammatory neurologic diseases, and 480 with noninflammatory neurologic diseases. Performances of KFLC<sub>CSF</sub>/Prot<sub>CSF</sub> in predicting OCB status, diagnosing MS, and estimating evolution of CIS to MS were evaluated and compared with those of other KFLC parameters, i.e., KFLC index, and with OCB and IgG parameters.</p><p><strong>Results: </strong>KFLC<sub>CSF</sub>/Prot<sub>CSF</sub> and KFLC index performed similarly in predicting OCB status, with a sensitivity of 80.2% and a specificity of 93.4% at a threshold >0.21% for KFLC<sub>CSF</sub>/Prot<sub>CSF</sub> (area under the curve: 0.93). The percentage of agreement between OCB status and KFLC<sub>CSF</sub>/Prot<sub>CSF</sub> was 91.2%. Using KFLC<sub>CSF</sub> and KFLC<sub>CSF</sub>/Prot<sub>CSF</sub> initially could reduce OCB testing by 68% and quantitative tests by 48.4%. For diagnosing MS/CIS, KFLC<sub>CSF</sub>/Prot<sub>CSF</sub> performed similar to or slightly worse than the KFLC index but always outperformed IgG, OCB, and KFLC<sub>CSF</sub>. For this indication, the optimal threshold for KFLC<sub>CSF</sub>/Prot<sub>CSF</sub> was >0.24%. It is important to note that KFLC<sub>CSF</sub>/Prot<sub>CSF</sub> was the most predictive parameter for CIS progression to MS.</p><p><strong>Discussion: </strong>To conclude, KFLC<sub>CSF</sub>/Prot<sub>CSF</sub> is as an easier and cost-effective alternative for predicting OCB status and CIS progression to MS and assisting in the diagnosis of MS.</p><p><strong>Classification of evidence: </strong>This study provides Class II evidence that the KFLC<sub>CSF</sub>/Protein<sub>CSF</sub> ratio accurately distinguishes patients with CSF OCBs from those without CSF OCBs and patients with MS from those with other neurologic disorders.</p>\",\"PeriodicalId\":19472,\"journal\":{\"name\":\"Neurology® Neuroimmunology & Neuroinflammation\",\"volume\":\"12 5\",\"pages\":\"e200451\"},\"PeriodicalIF\":7.5000,\"publicationDate\":\"2025-09-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12285672/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Neurology® Neuroimmunology & Neuroinflammation\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1212/NXI.0000000000200451\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/7/22 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neurology® Neuroimmunology & Neuroinflammation","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1212/NXI.0000000000200451","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/7/22 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
KFLC to Total CSF Protein Ratio Is an Alternative to KFLC Index to Diagnose Multiple Sclerosis: A Retrospective Study of 814 Cases.
Background and objectives: Biological analyses are crucial for diagnosing multiple sclerosis (MS), notably detection of oligoclonal bands (OCBs) of immunoglobulin G in CSF. Kappa free light chain (KFLC) quantification in serum and CSF has recently been proposed as an additional test. In a rational medicoeconomic approach, identifying algorithms or biomarkers is important. The objective of this study was, therefore, to evaluate the correlation between CSF kappa free light chain (KFLCCSF)/total CSF protein ratio (KFLCCSF/ProtCSF) and OCB status and its performance in diagnosing MS.
Methods: KFLC measurements were performed prospectively with each OCB analysis, and the data were interpreted retrospectively. A total of 814 clinical cases were included: 153 with MS or clinically isolated syndrome (CIS), 181 with other inflammatory neurologic diseases, and 480 with noninflammatory neurologic diseases. Performances of KFLCCSF/ProtCSF in predicting OCB status, diagnosing MS, and estimating evolution of CIS to MS were evaluated and compared with those of other KFLC parameters, i.e., KFLC index, and with OCB and IgG parameters.
Results: KFLCCSF/ProtCSF and KFLC index performed similarly in predicting OCB status, with a sensitivity of 80.2% and a specificity of 93.4% at a threshold >0.21% for KFLCCSF/ProtCSF (area under the curve: 0.93). The percentage of agreement between OCB status and KFLCCSF/ProtCSF was 91.2%. Using KFLCCSF and KFLCCSF/ProtCSF initially could reduce OCB testing by 68% and quantitative tests by 48.4%. For diagnosing MS/CIS, KFLCCSF/ProtCSF performed similar to or slightly worse than the KFLC index but always outperformed IgG, OCB, and KFLCCSF. For this indication, the optimal threshold for KFLCCSF/ProtCSF was >0.24%. It is important to note that KFLCCSF/ProtCSF was the most predictive parameter for CIS progression to MS.
Discussion: To conclude, KFLCCSF/ProtCSF is as an easier and cost-effective alternative for predicting OCB status and CIS progression to MS and assisting in the diagnosis of MS.
Classification of evidence: This study provides Class II evidence that the KFLCCSF/ProteinCSF ratio accurately distinguishes patients with CSF OCBs from those without CSF OCBs and patients with MS from those with other neurologic disorders.
期刊介绍：
Neurology Neuroimmunology & Neuroinflammation is an official journal of the American Academy of Neurology. Neurology: Neuroimmunology & Neuroinflammation will be the premier peer-reviewed journal in neuroimmunology and neuroinflammation. This journal publishes rigorously peer-reviewed open-access reports of original research and in-depth reviews of topics in neuroimmunology & neuroinflammation, affecting the full range of neurologic diseases including (but not limited to) Alzheimer's disease, Parkinson's disease, ALS, tauopathy, and stroke; multiple sclerosis and NMO; inflammatory peripheral nerve and muscle disease, Guillain-Barré and myasthenia gravis; nervous system infection; paraneoplastic syndromes, noninfectious encephalitides and other antibody-mediated disorders; and psychiatric and neurodevelopmental disorders. Clinical trials, instructive case reports, and small case series will also be featured.
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