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Article Dans Une Revue Neurology Neuroimmunology & Neuroinflammation Année : 2022

Kappa Free Light Chain Biomarkers Are Efficient for the Diagnosis of Multiple Sclerosis: A Large Multicenter Cohort Study

1 UCA Faculté Médecine - Université Côte d'Azur - Faculté de Médecine
2 URRIS UR2CA - Unité de Recherche Clinique de la Côte d’Azur
3 CHU Nîmes - Centre Hospitalier Universitaire de Nîmes
4 Département de neurologie [Montpellier]
5 HUS - Les Hôpitaux Universitaires de Strasbourg
6 Laboratoire de Biochimie [CHRU Nîmes]
7 Département de neurologie [Lille]
8 CHRU Lille - Centre Hospitalier Régional Universitaire [CHU Lille]
9 Infinity - Institut Toulousain des Maladies Infectieuses et Inflammatoires
10 CHU Toulouse - Centre Hospitalier Universitaire de Toulouse
11 Pôle Neurosciences [CHU Toulouse]
12 Institut Fédératif de Biologie (IFB)
13 Service de Neurologie [CHU de Saint-Étienne]
14 INMG - Institut NeuroMyoGène
15 CHU ST-E - Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne]
16 CHUGA - Centre Hospitalier Universitaire [CHU Grenoble]
17 TIMC-TrEE - Translational microbial Evolution and Engineering
18 Pathologie cellulaire : aspects moléculaires et viraux / Pathologie et Virologie Moléculaire
19 CEP - Centre d'épidémiologie des populations
20 Service de Biochimie [CHU de Dijon]
21 CHU Pitié-Salpêtrière [AP-HP]
22 CHU Trousseau [Tours]
23 U1064 Inserm - CR2TI - Centre de Recherche en Transplantation et Immunologie - Center for Research in Transplantation and Translational Immunology
24 U1064 Inserm - CR2TI - Team 5 : Neuroinflammation, mechanisms, therapeutic options (NEMO)
25 Laboratoire de Biochimie [CHU Nantes]
26 Hôpital Guillaume-et-René-Laennec [Saint-Herblain]
27 Département de Biochimie [CHU Nantes]
28 TIMONE - Hôpital de la Timone [CHU - APHM]
29 AMU - Aix Marseille Université
30 LA CONCEPTION - Hôpital de la Conception [CHU - APHM]
31 INS - Institut de Neurosciences des Systèmes
32 Hôpital Gui de Chauliac [CHU Montpellier]
33 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]
34 Centre d’Investigation Clinique Plurithématique (CIC - P) - CIC Strasbourg
35 CHU Strasbourg - Centre Hospitalier Universitaire [Strasbourg]
36 Laboratoire Immunologie [Nice]
37 IGF - Institut de Génomique Fonctionnelle
38 Service de Neurologie [CHU Nice]
Manon Rival
  • Fonction : Auteur
Jérôme de Sèze
  • Fonction : Auteur

Résumé

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.
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Dates et versions

inserm-04003586 , version 1 (24-02-2023)

Identifiants

Citer

Michael Levraut, Sabine Laurent-Chabalier, Xavier Ayrignac, Kévin Bigaut, Manon Rival, et al.. Kappa Free Light Chain Biomarkers Are Efficient for the Diagnosis of Multiple Sclerosis: A Large Multicenter Cohort Study. Neurology Neuroimmunology & Neuroinflammation, 2022, 10 (1), pp.e200049. ⟨10.1212/NXI.0000000000200049⟩. ⟨inserm-04003586⟩
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