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

C E Leurs; Ham Twaalfhoven; B I Lissenberg-Witte; V van Pesch; I Dujmovic; J Drulovic; M Castellazzi; T Bellini; M Pugliatti; J Kuhle; L M Villar; J C Alvarez-Cermeño; R Alvarez-Lafuente; H Hegen; F Deisenhammer; L M Walchhofer; E Thouvenot; M Comabella; X Montalban; L Vécsei; C Rajda; D Galimberti; E Scarpini; A Altintas; K Rejdak; J L Frederiksen; G Pihl-Jensen; Peh Jensen; M Khalil; M M Voortman; F Fazekas; A Saiz; D La Puma; M Vercammen; L Vanopdenbosch; Bmj Uitdehaag; J Killestein; C Bridel; C Teunissen

doi:10.1177/1352458519845844

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

C E Leurs, Ham Twaalfhoven, B I Lissenberg-Witte, V van Pesch, I Dujmovic, J Drulovic, M Castellazzi, T Bellini, M Pugliatti, J Kuhle, L M Villar, J C Alvarez-Cermeño, R Alvarez-Lafuente, H Hegen, F Deisenhammer, L M Walchhofer, E Thouvenot, M Comabella, X Montalban, L VécseiC Rajda, D Galimberti, E Scarpini, A Altintas, K Rejdak, J L Frederiksen, G Pihl-Jensen, Peh Jensen, M Khalil, M M Voortman, F Fazekas, A Saiz, D La Puma, M Vercammen, L Vanopdenbosch, Bmj Uitdehaag, J Killestein, C Bridel, C Teunissen

Afdeling for Hjerne- og Nervesygdomme NEU

84 Citationer (Scopus)

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.

Originalsprog	Engelsk
Tidsskrift	Multiple Sclerosis Journal
Vol/bind	26
Udgave nummer	8
Sider (fra-til)	912-923
Antal sider	12
ISSN	1352-4585
DOI	https://doi.org/10.1177/1352458519845844
Status	Udgivet - jul. 2020

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10.1177/1352458519845844

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Leurs, C. E., Twaalfhoven, H., Lissenberg-Witte, B. I., van Pesch, V., Dujmovic, I., Drulovic, J., Castellazzi, M., Bellini, T., Pugliatti, M., Kuhle, J., Villar, L. M., Alvarez-Cermeño, J. C., Alvarez-Lafuente, R., Hegen, H., Deisenhammer, F., Walchhofer, L. M., Thouvenot, E., Comabella, M., Montalban, X., ... Teunissen, C. (2020). Kappa free light chains is a valid tool in the diagnostics of MS: A large multicenter study. Multiple Sclerosis Journal, 26(8), 912-923. https://doi.org/10.1177/1352458519845844

Leurs, CE, Twaalfhoven, H, Lissenberg-Witte, BI, van Pesch, V, Dujmovic, I, Drulovic, J, Castellazzi, M, Bellini, T, Pugliatti, M, Kuhle, J, Villar, LM, Alvarez-Cermeño, JC, Alvarez-Lafuente, R, Hegen, H, Deisenhammer, F, Walchhofer, LM, Thouvenot, E, Comabella, M, Montalban, X, Vécsei, L, Rajda, C, Galimberti, D, Scarpini, E, Altintas, A, Rejdak, K, Frederiksen, JL , Pihl-Jensen, G, Jensen, P, Khalil, M, Voortman, MM, Fazekas, F, Saiz, A, La Puma, D, Vercammen, M, Vanopdenbosch, L, Uitdehaag, B, Killestein, J, Bridel, C & Teunissen, C 2020, 'Kappa free light chains is a valid tool in the diagnostics of MS: A large multicenter study', Multiple Sclerosis Journal, bind 26, nr. 8, s. 912-923. https://doi.org/10.1177/1352458519845844

@article{5b720b1348eb48b68d22cd5776d96233,

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

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.",

keywords = "Adult, Biomarkers/blood, Female, Humans, Immunoglobulin kappa-Chains/blood, Immunoglobulin lambda-Chains/blood, Male, Middle Aged, Multiple Sclerosis/diagnosis, Oligoclonal Bands/blood, Reproducibility of Results, Sensitivity and Specificity",

author = "Leurs, {C E} and Ham Twaalfhoven and Lissenberg-Witte, {B I} and {van Pesch}, V and I Dujmovic and J Drulovic and M Castellazzi and T Bellini and M Pugliatti and J Kuhle and Villar, {L M} and Alvarez-Cerme{\~n}o, {J C} and R Alvarez-Lafuente and H Hegen and F Deisenhammer and Walchhofer, {L M} and E Thouvenot and M Comabella and X Montalban and L V{\'e}csei and C Rajda and D Galimberti and E Scarpini and A Altintas and K Rejdak and Frederiksen, {J L} and G Pihl-Jensen and Peh Jensen and M Khalil and Voortman, {M M} and F Fazekas and A Saiz and {La Puma}, D and M Vercammen and L Vanopdenbosch and Bmj Uitdehaag and J Killestein and C Bridel and C Teunissen",

year = "2020",

month = jul,

doi = "10.1177/1352458519845844",

language = "English",

volume = "26",

pages = "912--923",

journal = "Multiple Sclerosis Journal",

issn = "1352-4585",

publisher = "SAGE Publications Ltd",

number = "8",

}

TY - JOUR

T1 - Kappa free light chains is a valid tool in the diagnostics of MS

T2 - A large multicenter study

AU - Leurs, C E

AU - Twaalfhoven, Ham

AU - Lissenberg-Witte, B I

AU - van Pesch, V

AU - Dujmovic, I

AU - Drulovic, J

AU - Castellazzi, M

AU - Bellini, T

AU - Pugliatti, M

AU - Kuhle, J

AU - Villar, L M

AU - Alvarez-Cermeño, J C

AU - Alvarez-Lafuente, R

AU - Hegen, H

AU - Deisenhammer, F

AU - Walchhofer, L M

AU - Thouvenot, E

AU - Comabella, M

AU - Montalban, X

AU - Vécsei, L

AU - Rajda, C

AU - Galimberti, D

AU - Scarpini, E

AU - Altintas, A

AU - Rejdak, K

AU - Frederiksen, J L

AU - Pihl-Jensen, G

AU - Jensen, Peh

AU - Khalil, M

AU - Voortman, M M

AU - Fazekas, F

AU - Saiz, A

AU - La Puma, D

AU - Vercammen, M

AU - Vanopdenbosch, L

AU - Uitdehaag, Bmj

AU - Killestein, J

AU - Bridel, C

AU - Teunissen, C

PY - 2020/7

Y1 - 2020/7

N2 - 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.

AB - 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.

KW - Adult

KW - Biomarkers/blood

KW - Female

KW - Humans

KW - Immunoglobulin kappa-Chains/blood

KW - Immunoglobulin lambda-Chains/blood

KW - Male

KW - Middle Aged

KW - Multiple Sclerosis/diagnosis

KW - Oligoclonal Bands/blood

KW - Reproducibility of Results

KW - Sensitivity and Specificity

U2 - 10.1177/1352458519845844

DO - 10.1177/1352458519845844

M3 - Journal article

C2 - 31066634

SN - 1352-4585

VL - 26

SP - 912

EP - 923

JO - Multiple Sclerosis Journal

JF - Multiple Sclerosis Journal

IS - 8

ER -

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

Abstract

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