RT Journal Article SR Electronic T1 Kappa Free Light Chain Biomarkers Are Efficient for the Diagnosis of Multiple Sclerosis JF Neurology - Neuroimmunology Neuroinflammation JO Neurol Neuroimmunol Neuroinflamm FD Lippincott Williams & Wilkins SP e200049 DO 10.1212/NXI.0000000000200049 VO 10 IS 1 A1 Levraut, Michael A1 Laurent-Chabalier, Sabine A1 Ayrignac, Xavier A1 Bigaut, Kévin A1 Rival, Manon A1 Squalli, Sanae A1 Zéphir, Hélène A1 Alberto, Tifanie A1 Pekar, Jean-David A1 Ciron, Jonathan A1 Biotti, Damien A1 Puissant-Lubrano, Bénédicte A1 Camdessanché, Jean-Philippe A1 Tholance, Yannick A1 Casez, Olivier A1 Toussaint, Bertrand A1 Marion, Jeanne A1 Moreau, Thibault A1 Lakomy, Daniela A1 Thomasset, Audrey A1 Maillart, Elisabeth A1 Sterlin, Delphine A1 Maurousset, Aude A1 Rocher, Auriane A1 Laplaud, David Axel A1 Bigot-Corbel, Edith A1 Bertho, Pierre-Olivier A1 Pelletier, Jean A1 Boucraut, Joseph A1 Labauge, Pierre A1 Vincent, Thierry A1 De Sèze, Jérôme A1 Jahn, Isabelle A1 Seitz-Polski, Barbara A1 Thouvenot, Eric A1 Lebrun-Frenay, Christine YR 2023 UL http://nn.neurology.org/content/10/1/e200049.abstract AB Background and Objectives Kappa free light chains (KFLC) seem to efficiently diagnose MS. However, extensive cohort studies are lacking to establish consensus cut-offs, notably to rule out non-MS autoimmune CNS disorders. Our objectives were to (1) determine diagnostic performances of CSF KFLC, KFLC index, and KFLC intrathecal fraction (IF) threshold values that allow us to separate MS from different CNS disorder control populations and compare them with oligoclonal bands' (OCB) performances and (2) to identify independent factors associated with KFLC quantification in MS.Methods We conducted a retrospective multicenter study involving 13 French MS centers. Patients were included if they had a noninfectious and nontumoral CNS disorder, eligible data concerning CSF and serum KFLC, albumin, and OCB. Patients were classified into 4 groups according to their diagnosis: MS, clinically isolated syndrome (CIS), other inflammatory CNS disorders (OIND), and noninflammatory CNS disorder controls (NINDC).Results One thousand six hundred twenty-one patients were analyzed (675 MS, 90 CIS, 297 OIND, and 559 NINDC). KFLC index and KFLC IF had similar performances in diagnosing MS from nonselected controls and OIND (p = 0.123 and p = 0.991 for area under the curve [AUC] comparisons) and performed better than CSF KFLC (p < 0.001 for all AUC comparisons). A KFLC index of 8.92 best separated MS/CIS from the entire nonselected control population, with better performances than OCB (p < 0.001 for AUC comparison). A KFLC index of 11.56 best separated MS from OIND, with similar performances than OCB (p = 0.065). In the multivariate analysis model, female gender (p = 0.003), young age (p = 0.013), and evidence of disease activity (p < 0.001) were independent factors associated with high KFLC index values in patients with MS, whereas MS phenotype, immune-modifying treatment use at sampling, and the FLC analyzer type did not influence KFLC index.Discussion KFLC biomarkers are efficient tools to separate patients with MS from controls, even when compared with other patients with CNS autoimmune disorder. Given these results, we suggest using KFLC index or KFLC IF as a criterion to diagnose MS.Classification of Evidence This study provides Class III evidence that KFLC index or IF can be used to differentiate patients with MS from nonselected controls and from patients with other autoimmune CNS disorders.AUC=area under the curve; CIS=clinically isolated syndrome; FLC=free light chain; IF=intrathecal fraction; KFLC=Kappa free light chain; LDL=lower detectable limit; LFLC=lambda FLC; NINDC=noninflammatory CNS disorder control; OCB=oligoclonal band; OIND=other inflammatory CNS disorder; SC=symptomatic control