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

被引：80

作者：

Leurs, C. E. ^{[1
,2
]}

Twaalfhoven, H. A. m ^{[3
,4
]}

Lissenberg-Witte, B., I ^{[5
]}

van Pesch, V ^{[6
]}

Dujmovic, I ^{[7
]}

Drulovic, J. ^{[7
]}

Castellazzi, M. ^{[8
]}

Bellini, T. ^{[8
]}

Pugliatti, M. ^{[8
]}

Kuhle, J. ^{[9
,10
,11
]}

Villar, L. M. ^{[12
,13
]}

Alvarez-Cermeno, J. C. ^{[13
,14
]}

Alvarez-Lafuente, R. ^{[13
,15
]}

Hegen, H. ^{[16
]}

Deisenhammer, F. ^{[16
]}

Walchhofer, L. M. ^{[16
]}

Thouvenot, E. ^{[17
,18
]}

Comabella, M. ^{[19
]}

Montalban, X. ^{[19
]}

Vecsei, L. ^{[20
,21
]}

Rajda, C. ^{[20
]}

Galimberti, D. ^{[22
]}

Scarpini, E. ^{[22
]}

Altintas, A. ^{[23
]}

Rejdak, K. ^{[24
]}

Frederiksen, J. L. ^{[25
,26
]}

Pihl-Jensen, G. ^{[25
,26
]}

Jensen, P. E. H. ^{[27
]}

Khalil, M. ^{[28
]}

Voortman, M. M. ^{[28
]}

Fazekas, F. ^{[28
]}

Saiz, A. ^{[29
,30
]}

La Puma, D. ^{[29
,30
]}

Vercammen, M. ^{[31
]}

Vanopdenbosch, L. ^{[32
]}

Uitdehaag, B. M. J. ^{[2
]}

Killestein, J. ^{[2
]}

Bridel, C. ^{[3
,4
]}

Teunissen, C. ^{[3
,4
]}

机构：

[1] Vrije Univ Amsterdam Med Ctr, MS Ctr Amsterdam, Dept Neurol, De Boelelaan 1118, NL-1081 HZ Amsterdam, Netherlands

[2] Amsterdam UMC, MS Ctr Amsterdam, Dept Neurol, Amsterdam Neurosci,Locat VUmc, Amsterdam, Netherlands

[3] Amsterdam UMC, Dept Clin Chem, Neurochem Lab, MS Ctr Amsterdam,Amsterdam Neurosci,Locat VUmc, Amsterdam, Netherlands

[4] Amsterdam UMC, Dept Clin Chem, Biobank, MS Ctr Amsterdam,Amsterdam Neurosci,Locat VUmc, Amsterdam, Netherlands

[5] Amsterdam UMC, Locat VUmc, Dept Epidemiol & Biostat, Amsterdam, Netherlands

[6] Catholic Univ Louvain, Clin Unive St Luc, Dept Neurol, Sint Lambrechts Woluwe, Belgium

[7] Univ Belgrade, Clin Ctr Serbia, Sch Med, Clin Neurol, Belgrade, Serbia

[8] Univ Ferrara, Dept Biomed & Specialty Surg Sci, Ferrara, Italy

[9] Univ Basel, Univ Hosp Basel, Dept Med, Neurol Clin & Policlin, Basel, Switzerland

[10] Univ Basel, Univ Hosp Basel, Dept Clin Res, Neurol Clin & Policlin, Basel, Switzerland

[11] Univ Basel, Univ Hosp Basel, Dept Biomed, Neurol Clin & Policlin, Basel, Switzerland

[12] Hosp Ramon & Cajal, Dept Immunol, IRYCIS, Madrid, Spain

[13] Red Espanola Esclerosis Multiple REEM, Madrid, Spain

[14] Hosp Ramon & Cajal, Dept Neurol, IRYICIS, Madrid, Spain

[15] Hosp Clin San Carlos, Inst Invest Sanitaria San Carlos IdISSC, Grp Invest Esclerosis Multiple, Madrid, Spain

[16] Med Univ Innsbruck, Dept Neurol, Innsbruck, Austria

[17] CHU Nimes, Hop Caremeau, Dept Neurol, Nimes, France

[18] Univ Montpellier, Inst Genom Fonct, UMR5203, Montpellier, France

[19] Univ Autonoma Barcelona, Hosp Univ Vall dHebron, Ctr Esclerosi Multiple Catalunya Cemcat, Inst Recerca Vall dHebron VHIR,Serv Neurol Neuroi, Barcelona, Spain

[20] Univ Szeged, Dept Neurol, Szeged, Hungary

[21] MTA SZTE Neurosci Res Grp, Szeged, Hungary

[22] Univ Milan, Fdn Ca Granda, Multiple Sclerosis Ctr, Dino Ferrari Ctr,IRCCS Osped Policlin, Milan, Italy

[23] Koc Univ, Sch Med, Neurol Dept, Istanbul, Turkey

[24] Med Univ Lublin, Dept Neurol, Lublin, Poland

[25] Rigshosp Glostrup, Dept Neurol, Copenhagen, Denmark

[26] Univ Copenhagen, Copenhagen, Denmark

[27] Univ Copenhagen, Rigshosp, Danish Multiple Sclerosis Ctr, Dept Neurol, Copenhagen, Denmark

[28] Med Univ Graz, Dept Neurol, Graz, Austria

[29] Inst Invest Biomed August Pi i Sunyer IDIBAP, Hosp Clin, Ctr Neuroimmunol, Serv Neurol, Barcelona, Spain

[30] Univ Barcelona, Barcelona, Spain

[31] AZ Sint Jan Brugge Oostende, Dept Lab Med, Brugge, Belgium

[32] AZ Sint Jan Brugge Oostende, Dept Neurol, Brugge, Belgium

来源：

MULTIPLE SCLEROSIS JOURNAL | 2020年 / 26卷 / 08期

关键词：

Multiple sclerosis; KFLC; OCB; CSF; biomarkers; MULTIPLE-SCLEROSIS DIAGNOSIS; CLINICALLY ISOLATED SYNDROME; CEREBROSPINAL-FLUID; BIOMARKER; GUIDELINES; REVISIONS; UTILITY; INDEX; SERUM; KFLC;

D O I：

10.1177/1352458519845844

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

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.

引用

页码：912 / 923

页数：12

共 34 条

[1] Utility of oligoclonal IgG band detection for MS diagnosis in daily clinical practice [J].

Abraira, V. ;

Alvarez-Cermeno, J. C. ;

Arroyo, R. ;

Camara, C. ;

Casanova, B. ;

Cubillo, S. ;

de Andres, C. ;

Espejo, C. ;

Fernandez, O. ;

Ferrer, J. ;

Figueredo, M. A. ;

Garcia-Merino, A. ;

Garcia-Sanchez, M. I. ;

Garcia-Trujillo, J. A. ;

Gomez, M. ;

Gonzalez-Oria, C. ;

Gosis, A. ;

Izquierdo, G. ;

Jimenez, J. ;

Lopez-Trascasa, M. ;

Montalban, X. ;

Moreno, M. J. ;

Munoz, D. ;

Nunez, V. ;

Muriel, A. ;

Navarro, J. ;

Olascoaga, J. ;

Oreja-Guevara, C. ;

Prada, A. ;

Ramil, E. ;

Ramo-Tello, C. ;

Rodriguez, C. ;

Rodriguez, E. ;

Rodriguez-Frias, F. ;

Rodriguez-Antigueedad, A. ;

Rodriguez-Molina, J. J. ;

Ruiz, E. ;

Saiz, A. ;

Sarasola, E. ;

Simo, M. ;

Yaguee, J. ;

Villar, L. M. .

JOURNAL OF IMMUNOLOGICAL METHODS, 2011, 371 (1-2) :170-173

[2]

Arrambide G, 2017, ECTRIMS, V2017, P202450

[3] FREE LIGHT-CHAINS IN THE CSF IN MULTIPLE-SCLEROSIS [J].

BRACCO, F ;

GALLO, P ;

MENNA, R ;

BATTISTIN, L ;

TAVOLATO, B .

JOURNAL OF NEUROLOGY, 1987, 234 (05) :303-307

[4]

Bradwell AR, 2001, CLIN CHEM, V47, P673

[5] FREE LIGHT-CHAINS IN MULTIPLE-SCLEROSIS AND INFECTIONS OF THE CNS [J].

DECARLI, C ;

MENEGUS, MA ;

RUDICK, RA .

NEUROLOGY, 1987, 37 (08) :1334-1338

[6] Quantification of immunoglobulin free light chains in cerebrospinal fluid by nephelometry [J].

Desplat-Jégo, S ;

Feuillet, L ;

Pelletier, J ;

Bernard, D ;

Chérif, AA ;

Boucraut, J .

JOURNAL OF CLINICAL IMMUNOLOGY, 2005, 25 (04) :338-345

[7] Determination of kFLC and K Index in cerebrospinal fluid: A valid alternative to assessintrathecal immunoglobulin synthesis [J].

Duranti, Fabio ;

Pieri, Massimo ;

Centonze, Diego ;

Buttari, Fabio ;

Bernardini, Sergio ;

Dessi, Mariarita .

JOURNAL OF NEUROIMMUNOLOGY, 2013, 263 (1-2) :116-120

[8] Guidelines for uniform reporting of body fluid biomarker studies in neurologic disorders [J].

Gnanapavan, Sharmilee ;

Hegen, Harald ;

Khalil, Michael ;

Hemmer, Bernhard ;

Franciotta, Diego ;

Hughes, Steve ;

Hintzen, Rogier ;

Jeromin, Andreas ;

Havrdova, Eva ;

Tumani, Hayrettin ;

Bertolotto, Antonio ;

Comabella, Manuel ;

Frederiksen, Jette ;

Alvarez-Cermeno, Jose C. ;

Villar, Luisa ;

Galimberti, Daniela ;

Myhr, Kjell-Morten ;

Dujmovic, Irena ;

Fazekas, Franz ;

Ionete, Carolina ;

Menge, Til ;

Kuhle, Jens ;

Keir, Geoffrey ;

Deisenhammer, Florian ;

Teunissen, Charlotte ;

Giovannoni, Gavin .

NEUROLOGY, 2014, 83 (13) :1210-1216

[9] Free light chain monomer-dimer patterns in the diagnosis of multiple sclerosis [J].

Kaplan, Batia ;

Golderman, Sizilia ;

Yahalom, Gilad ;

Yeskaraev, Regina ;

Ziv, Tamar ;

Aizenbud, Boris M. ;

Sela, Ben-Ami ;

Livneh, Avi .

JOURNAL OF IMMUNOLOGICAL METHODS, 2013, 390 (1-2) :74-80

[10] Free light chain monomers in the diagnosis of multiple sclerosis [J].

Kaplan, Batia ;

Aizenbud, Boris M. ;

Golderman, Sizilia ;

Yaskariev, Regina ;

Sela, Ben-Ami .

JOURNAL OF NEUROIMMUNOLOGY, 2010, 229 (1-2) :263-271

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