Diagnostic Value of the Kappa Free Light Chain Index to Distinguish MOGAD, NMOSD, and MS

BACKGROUND AND OBJECTIVES: The differential diagnosis between aquaporin-4-immunoglobulin G-positive neuromyelitis optica spectrum disorder (AQP4-NMOSD), myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD), and multiple sclerosis (MS) can be complex. Kappa free light chain index (KFLC-Index) emerged as an effective biomarker for distinguishing patients with MS from patients with other conditions. The main aim of this study was to assess the diagnostic performance of KFLC-Index in differentiating MOGAD, AQP4-NMOSD, and MS and to compare it with CSF-restricted oligoclonal bands (OCB) performance. METHODS: We conducted a retrospective case-control study involving 18 French centers through our national NOMADMUS database. Patients were eligible if they received MOGAD or AQP4-NMOSD diagnosis and if OCB status and KFLC-Index levels were available or could be measured retrospectively. As a comparator, we included a group of patients with MS from the Lyon center. RESULTS: We included 303 patients with 140 MOGAD, 37 AQP4-NMOSD, and 126 MS. The sex ratio F/M was 1/1 in the MOGAD group, 5/1 in the NMOSD group, and 4/1 in the MS group. The median age was 38 years in the MOGAD group, 52 in the NMOSD group, and 32 in the MS group. The median KFLC-Index (interquartile range) was the lowest in the MOGAD group (0.60 [0.33-2.09]) with 71% of undetectable CSF-KFLC, intermediate in the NMOSD group (8.85 [3.04-16.78]), and the highest in the MS group (49.90 [16.31-113.39]). KFLC-Index had very good diagnostic performance in differentiating MOGAD from MS (area under the curve [AUC] 0.93, 95% CI 0.9-0.96) with an optimal threshold of 5.7 (95% CI 4.74-6.85), a sensitivity of 0.89 (0.83-0.94), and a specificity of 0.89 (0.83-0.94). KFLC-Index had good performance in differentiating NMOSD from MS (AUC 0.82, 95% CI 0.74-0.88) and MOGAD from NMOSD (AUC 0.77, 95% CI 0.69-0.86). KFLC-Index did not significantly outperformed OCB in separating MOGAD from MS and NMOSD from MS; however, the combination of the 2 tests was more performant than used separately. DISCUSSION: KFLC-Index is a valuable tool in distinguishing MS from AQP4-NMOSD and MOGAD and provides additional information to that given by OCB. We suggest that KFLC-Index as an additional supporting criterion for the differential diagnosis between MOGAD and MS.

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Journal
Neurology
Published
2026-04-01
DOI
https://doi.org/10.1212/wnl.0000000000214806
Citations
1
Primary Topic
Multiple Sclerosis Research Studies
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article
Field-Weighted Citation Impact
20.70
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article

Diagnostic Value of the Kappa Free Light Chain Index to Distinguish MOGAD, NMOSD, and MS

Romain Deschamps, Xavier Ayrignac, Jonathan Ciron, Pierre Branger et al.
1 citations
Neurology
Multiple Sclerosis Research Studies
20.70
article

Diagnostic Value of the Kappa Free Light Chain Index to Distinguish MOGAD, NMOSD, and MS

Romain Deschamps, Xavier Ayrignac, Jonathan Ciron, Pierre Branger, Julie Pique, Élisabeth Maillart, Apolline Tournier, C. Giannesini, Sarah Demortière, Chloé Bost, Antoine Gavoille, Frédéric Klapczynski, M. Cohen, Sanae Squalli, Hélène Zéphir, Denis Maréchal, Michaël Levraut, Nicolas Collongues, Delphine Sterlin, Clémence Boutière, Eléonore Micoud, N. Mélé, B. Audoin, José Boucraut, Barbara Seitz-Polski, Sandra Vukusic, Romain Marignier, David Axel Laplaud, Eric Thouvenot, Thomas Drouet, Alexandre Jentzer, Guido Ahle
article en
1 citations

Abstract

BACKGROUND AND OBJECTIVES: The differential diagnosis between aquaporin-4-immunoglobulin G-positive neuromyelitis optica spectrum disorder (AQP4-NMOSD), myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD), and multiple sclerosis (MS) can be complex. Kappa free light chain index (KFLC-Index) emerged as an effective biomarker for distinguishing patients with MS from patients with other conditions. The main aim of this study was to assess the diagnostic performance of KFLC-Index in differentiating MOGAD, AQP4-NMOSD, and MS and to compare it with CSF-restricted oligoclonal bands (OCB) performance. METHODS: We conducted a retrospective case-control study involving 18 French centers through our national NOMADMUS database. Patients were eligible if they received MOGAD or AQP4-NMOSD diagnosis and if OCB status and KFLC-Index levels were available or could be measured retrospectively. As a comparator, we included a group of patients with MS from the Lyon center. RESULTS: We included 303 patients with 140 MOGAD, 37 AQP4-NMOSD, and 126 MS. The sex ratio F/M was 1/1 in the MOGAD group, 5/1 in the NMOSD group, and 4/1 in the MS group. The median age was 38 years in the MOGAD group, 52 in the NMOSD group, and 32 in the MS group. The median KFLC-Index (interquartile range) was the lowest in the MOGAD group (0.60 [0.33-2.09]) with 71% of undetectable CSF-KFLC, intermediate in the NMOSD group (8.85 [3.04-16.78]), and the highest in the MS group (49.90 [16.31-113.39]). KFLC-Index had very good diagnostic performance in differentiating MOGAD from MS (area under the curve [AUC] 0.93, 95% CI 0.9-0.96) with an optimal threshold of 5.7 (95% CI 4.74-6.85), a sensitivity of 0.89 (0.83-0.94), and a specificity of 0.89 (0.83-0.94). KFLC-Index had good performance in differentiating NMOSD from MS (AUC 0.82, 95% CI 0.74-0.88) and MOGAD from NMOSD (AUC 0.77, 95% CI 0.69-0.86). KFLC-Index did not significantly outperformed OCB in separating MOGAD from MS and NMOSD from MS; however, the combination of the 2 tests was more performant than used separately. DISCUSSION: KFLC-Index is a valuable tool in distinguishing MS from AQP4-NMOSD and MOGAD and provides additional information to that given by OCB. We suggest that KFLC-Index as an additional supporting criterion for the differential diagnosis between MOGAD and MS.

NeurologyVol. 106(8)
Université Claude Bernard Lyon 1 (FR), Centre National de la Recherche Scientifique (FR), Inserm (FR), Université de Lille (FR), Centre Hospitalier Universitaire de Lille (FR), Centre Hospitalier Universitaire de Nice (FR), Centre Hospitalier Universitaire de Nantes (FR), Centre Hospitalier Universitaire de Toulouse (FR), Sorbonne Université (FR), Hopitaux Civils de Colmar (FR), Centre Hospitalier Universitaire de Montpellier (FR), Assistance Publique – Hôpitaux de Paris (FR), Hospices Civils de Lyon (FR), Observatoire Français de la Sclérose en Plaques (FR), Centre Hospitalier Universitaire de Nîmes (FR), Hôpital Pierre Wertheimer (FR), Centre de Recherche en Neurobiologie - Neurophysiologie de Marseille (FR), Hôpital Gui de Chauliac (FR), Centre de Neurophysique Physiologie et Pathologie (FR), Pitié-Salpêtrière Hospital (FR), Centre Hospitalier Sainte-Anne (FR), Fondation de Rothschild (FR), Centre d'Investigation Clinique de Nantes (FR), Centre d'Immunologie et des Maladies Infectieuses (FR), Centre Hospitalier Régional Universitaire de Brest (FR), Laboratoire de Biométrie et Biologie Evolutive (FR), Hôpital Pasteur (FR), FHU Neurovasc (FR), Institut du Cerveau (FR), Hôpital Maison Blanche (FR), Hôpital Broussais (FR), Université de Strasbourg (FR), Nantes Université (FR), Université de Caen Normandie (FR)
Openalex Percentile: Top 1%
Multiple Sclerosis Research Studies
20.70
DOIOpen Access PDFOpenAlex
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