Kappa free light chains is a valid tool in the diagnostics of MS: A large multicenter study

Author:

Leurs CE1,Twaalfhoven HAM2,Lissenberg-Witte BI3,van Pesch V4,Dujmovic I5,Drulovic J5,Castellazzi M6ORCID,Bellini T6,Pugliatti M6,Kuhle J7,Villar LM8,Alvarez-Cermeño JC9,Alvarez-Lafuente R10ORCID,Hegen H11,Deisenhammer F11ORCID,Walchhofer LM11,Thouvenot E12,Comabella M13,Montalban X13,Vécsei L14,Rajda C15,Galimberti D16,Scarpini E16,Altintas A17,Rejdak K18,Frederiksen JL19,Pihl-Jensen G19,Jensen PEH20,Khalil M21ORCID,Voortman MM21ORCID,Fazekas F21,Saiz A22ORCID,La Puma D22,Vercammen M23,Vanopdenbosch L24,Uitdehaag BMJ25,Killestein J25,Bridel C2,Teunissen C2

Affiliation:

1. Department of Neurology, MS Center Amsterdam, VU University Medical Center, De Boelelaan 1118, Amsterdam 1081 HZ, The Netherlands

2. Neurochemistry Laboratory and Biobank, Department of Clinical Chemistry, MS Center Amsterdam, Amsterdam Neuroscience, Amsterdam UMC, location VUmc, Amsterdam, The Netherlands

3. Department of Epidemiology and Biostatistics, Amsterdam UMC, location VUmc, Amsterdam, The Netherlands

4. Department of Neurology, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Sint-Lambrechts-Woluwe, Belgium

5. Clinic of Neurology, Clinical Centre of Serbia, School of Medicine, University of Belgrade, Belgrade, Serbia

6. Department of Biomedical and Specialty Surgical Sciences, University of Ferrara, Ferrara, Italy

7. Neurologic Clinic and Policlinic, Departments of Medicine, Clinical Research and Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland

8. Department of Immunology, Hospital Ramón y Cajal, IRYCIS, Madrid, Spain/ Red Española de Esclerosis Múltiple (REEM), Madrid, Spain

9. Red Española de Esclerosis Múltiple (REEM), Madrid, Spain/Department of Neurology, Hospital Ramón y Cajal, IRYICIS, Madrid, Spain

10. Red Española de Esclerosis Múltiple (REEM), Madrid, Spain/Grupo de Investigación de Esclerosis Múltiple, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria San Carlos (IdISSC), Madrid, Spain

11. Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria

12. Department of Neurology, CHU Nîmes, Hôpital Caremeau, Nîmes, France/Institut de Génomique Fonctionnelle, UMR5203, Université Montpellier, Montpellier, France

13. Servei de Neurologia-Neuroimmunologia, Centre d’Esclerosi Múltiple de Catalunya (Cemcat), Institut de Recerca Vall d’Hebron (VHIR), Hospital Universitari Vall d’Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain

14. Department of Neurology, University of Szeged, Szeged, Hungary/MTA-SZTE Neuroscience Research Group, Szeged, Hungary

15. Department of Neurology, University of Szeged, Szeged, Hungary

16. Multiple Sclerosis Centre, University of Milan, Dino Ferrari Centre, Fondazione Ca’ Granda, IRCCS Ospedale Policlinico, Milan, Italy

17. Koc University, School of Medicine, Neurology Department, Istanbul, Turkey

18. Department of Neurology, Medical University of Lublin, Lublin, Poland

19. Department of Neurology, Rigshospitalet Glostrup and University of Copenhagen, Copenhagen, Denmark

20. Danish Multiple Sclerosis Centre, Department of Neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

21. Department of Neurology, Medical University of Graz, Graz, Austria

22. Center of Neuroimmunology, Service of Neurology, Hospital Clinic, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) and Universitat de Barcelona, Barcelona, Spain

23. Department of Laboratory Medicine, AZ Sint-Jan Brugge-Oostende, Brugge, Belgium

24. Department of Neurology, AZ Sint-Jan Brugge-Oostende, Brugge, Belgium

25. Department of Neurology, MS Center Amsterdam, Amsterdam Neuroscience, Amsterdam UMC, location VUmc, Amsterdam, The Netherlands

Abstract

Objective: To validate kappa free light chain (KFLC) and lambda free light chain (LFLC) indices as a diagnostic biomarker in multiple sclerosis (MS). Methods: We performed a multicenter study including 745 patients from 18 centers (219 controls and 526 clinically isolated syndrome (CIS)/MS patients) with a known oligoclonal IgG band (OCB) status. KFLC and LFLC were measured in paired cerebrospinal fluid (CSF) and serum samples. Gaussian mixture modeling was used to define a cut-off for KFLC and LFLC indexes. Results: The cut-off for the KFLC index was 6.6 (95% confidence interval (CI) = 5.2–138.1). The cut-off for the LFLC index was 6.9 (95% CI = 4.5–22.2). For CIS/MS patients, sensitivity of the KFLC index (0.88; 95% CI = 0.85–0.90) was higher than OCB (0.82; 95%CI = 0.79–0.85; p < 0.001), but specificity (0.83; 95% CI = 0.78–0.88) was lower (OCB = 0.92; 95% CI = 0.89–0.96; p < 0.001). Both sensitivity and specificity for the LFLC index were lower than OCB. Conclusion: Compared with OCB, the KFLC index is more sensitive but less specific for diagnosing CIS/MS. Lacking an elevated KFLC index is more powerful for excluding MS compared with OCB but the latter is more important for ruling in a diagnosis of CIS/MS.

Publisher

SAGE Publications

Subject

Clinical Neurology,Neurology

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