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

C. E. Leurs; H. A. M. 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; P. E. H. Jensen; M. Khalil; M. M. Voortman; F. Fazekas; A. Saiz; D. La Puma; M. Vercammen; L. Vanopdenbosch; B. M. J. 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, H. A. M. 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, P. E. H. Jensen, M. Khalil, M. M. Voortman, F. Fazekas, A. Saiz, D. La Puma, M. Vercammen, L. Vanopdenbosch, B. M. J. Uitdehaag, J. Killestein, C. Bridel, C. Teunissen

Research output: Contribution to journal › Journal article › peer-review

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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.

Original language	English
Journal	Multiple Sclerosis Journal
Volume	26
Issue number	8
Pages (from-to)	912-923
Number of pages	12
ISSN	1352-4585
DOIs	https://doi.org/10.1177/1352458519845844
Publication status	Published - 2020

Keywords

biomarkers
CSF
KFLC
Multiple sclerosis
OCB

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Leurs, C. E., Twaalfhoven, H. A. M., 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

Kappa free light chains is a valid tool in the diagnostics of MS : A large multicenter study. / Leurs, C. E.; Twaalfhoven, H. A. M.; 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.; Vécsei, L.; Rajda, C.; Galimberti, D.; Scarpini, E.; Altintas, A.; Rejdak, K.; Frederiksen, J. L.; Pihl-Jensen, G.; Jensen, P. E. H.; Khalil, M.; Voortman, M. M.; Fazekas, F.; Saiz, A.; La Puma, D.; Vercammen, M.; Vanopdenbosch, L.; Uitdehaag, B. M. J.; Killestein, J.; Bridel, C.; Teunissen, C.

In: Multiple Sclerosis Journal, Vol. 26, No. 8, 2020, p. 912-923.

Research output: Contribution to journal › Journal article › peer-review

Leurs, CE, Twaalfhoven, HAM, 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, PEH, Khalil, M, Voortman, MM, Fazekas, F, Saiz, A, La Puma, D, Vercammen, M, Vanopdenbosch, L, Uitdehaag, BMJ, 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, vol. 26, no. 8, pp. 912-923. https://doi.org/10.1177/1352458519845844

Leurs, C. E. ; Twaalfhoven, H. A. M. ; 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. ; Vécsei, L. ; Rajda, C. ; Galimberti, D. ; Scarpini, E. ; Altintas, A. ; Rejdak, K. ; Frederiksen, J. L. ; Pihl-Jensen, G. ; Jensen, P. E. H. ; Khalil, M. ; Voortman, M. M. ; Fazekas, F. ; Saiz, A. ; La Puma, D. ; Vercammen, M. ; Vanopdenbosch, L. ; Uitdehaag, B. M. J. ; Killestein, J. ; Bridel, C. ; Teunissen, C. / Kappa free light chains is a valid tool in the diagnostics of MS : A large multicenter study. In: Multiple Sclerosis Journal. 2020 ; Vol. 26, No. 8. pp. 912-923.

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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 = "biomarkers, CSF, KFLC, Multiple sclerosis, OCB",

author = "Leurs, {C. E.} and Twaalfhoven, {H. A. M.} 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 Jensen, {P. E. H.} and M. Khalil and Voortman, {M. M.} and F. Fazekas and A. Saiz and {La Puma}, D. and M. Vercammen and L. Vanopdenbosch and Uitdehaag, {B. M. J.} and J. Killestein and C. Bridel and C. Teunissen",

year = "2020",

doi = "10.1177/1352458519845844",

language = "English",

volume = "26",

pages = "912--923",

journal = "Multiple Sclerosis Journal",

issn = "1352-4585",

publisher = "SAGE Publications",

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, H. A. M.

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, P. E. H.

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, B. M. J.

AU - Killestein, J.

AU - Bridel, C.

AU - Teunissen, C.

PY - 2020

Y1 - 2020

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 - biomarkers

KW - CSF

KW - KFLC

KW - Multiple sclerosis

KW - OCB

U2 - 10.1177/1352458519845844

DO - 10.1177/1352458519845844

M3 - Journal article

C2 - 31066634

AN - SCOPUS:85065731162

VL - 26

SP - 912

EP - 923

JO - Multiple Sclerosis Journal

JF - Multiple Sclerosis Journal

SN - 1352-4585

IS - 8

ER -