Predicting aggressive multiple sclerosis with intrathecal IgM synthesis among patients with a clinically isolated syndrome

Enric  Monreal; Susana  Sainz de la Maza; Lucienne  Costa-Frossard; Paulette  Walo-Delgado; Javier Zamora; Jose Ignacio  Fernandez-Velasco; Noelia  Villarrubia; Mercedes  Espiño; Daniel  Lourido; Paloma  Lapuente; Inmaculada  Toboso; Jose Carlos  Alvarez-Cermeño; Jaime Masjuan; Luisa Marıa  Villar

doi:10.1212/NXI.0000000000001047

Predicting aggressive multiple sclerosis with intrathecal IgM synthesis among patients with a clinically isolated syndrome

Enric Monreal, Susana Sainz de la Maza, Lucienne Costa-Frossard, Paulette Walo-Delgado, Javier Zamora, Jose Ignacio Fernandez-Velasco, Noelia Villarrubia, Mercedes Espiño, Daniel Lourido, Paloma Lapuente, Inmaculada Toboso, Jose Carlos Alvarez-Cermeño, Jaime Masjuan, Luisa Marıa Villar

Applied Health Research

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Abstract

Objective: To determine the best method to measure intrathecal immunoglobulin (Ig) M synthesis(ITMS), a biomarker of worse prognosis in multiple sclerosis (MS). We compared the ability for predicting a poor evolution of 4 methods assessing ITMS (IgM oligoclonal bands[OCMBs], lipid-specific OCMBs [LS-OCMBs], Reibergram, and IgM index) in patients with aclinically isolated syndrome (CIS).

Methods: Prospective study with consecutive patients performed at a referral MS center. We used unadjusted and multivariate Cox regressions for predicting a second relapse, Expanded Disability Status Scale (EDSS) scores of 4 and 6, and development of secondary progressive MS(SPMS).

Results: A total of 193 patients were included, with a median (interquartile range) age of 31 (25–38) years and a median follow-up of 12.9 years. Among all methods, only OCMB, LS-OCMB, and Reibergram significantly identified patients at risk of some of the pre-established outcomes,being LS-OCMB the technique with the strongest associations. Adjusted hazard ratio (aHR) ofLS-OCMB for predicting a second relapse was 2.50 (95% CI 1.72–3.64, p < 0.001). The risk of reaching EDSS scores of 4 and 6 and SPMS was significantly higher among patients with LSOCMB (aHR 2.96, 95% CI 1.54–5.71, p = 0.001; aHR 4.96, 95% CI 2.22–11.07, p < 0.001; and aHR 2.31, 95% CI 1.08–4.93, p = 0.03, respectively).

Conclusions: ITMS predicts an aggressive MS at disease onset, especially when detected as LS-OCMB.

Classification of Evidence: This study provides Class II evidence that lipid-specific IgM oligoclonal bands can predict progression from CIS to MS and a worse disease course over a follow-up of at least 2 years

Original language	English
Article number	e1047
Number of pages	12
Journal	Neurology: Neuroimmunology and NeuroInflammation
Volume	8
Issue number	5
DOIs	https://doi.org/10.1212/NXI.0000000000001047
Publication status	Published - 22 Jul 2021

ASJC Scopus subject areas

Neurology
Clinical Neurology

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Monreal, E., Sainz de la Maza, S., Costa-Frossard, L., Walo-Delgado, P., Zamora, J., Fernandez-Velasco, J. I., Villarrubia, N., Espiño, M., Lourido, D., Lapuente, P., Toboso, I., Alvarez-Cermeño, J. C., Masjuan, J., & Villar, L. M. (2021). Predicting aggressive multiple sclerosis with intrathecal IgM synthesis among patients with a clinically isolated syndrome. Neurology: Neuroimmunology and NeuroInflammation, 8(5), Article e1047. https://doi.org/10.1212/NXI.0000000000001047

@article{f3fac638e27a4fbbb1441cc3aa4ba62d,

title = "Predicting aggressive multiple sclerosis with intrathecal IgM synthesis among patients with a clinically isolated syndrome",

abstract = "Objective: To determine the best method to measure intrathecal immunoglobulin (Ig) M synthesis(ITMS), a biomarker of worse prognosis in multiple sclerosis (MS). We compared the ability for predicting a poor evolution of 4 methods assessing ITMS (IgM oligoclonal bands[OCMBs], lipid-specific OCMBs [LS-OCMBs], Reibergram, and IgM index) in patients with aclinically isolated syndrome (CIS).Methods: Prospective study with consecutive patients performed at a referral MS center. We used unadjusted and multivariate Cox regressions for predicting a second relapse, Expanded Disability Status Scale (EDSS) scores of 4 and 6, and development of secondary progressive MS(SPMS).Results: A total of 193 patients were included, with a median (interquartile range) age of 31 (25–38) years and a median follow-up of 12.9 years. Among all methods, only OCMB, LS-OCMB, and Reibergram significantly identified patients at risk of some of the pre-established outcomes,being LS-OCMB the technique with the strongest associations. Adjusted hazard ratio (aHR) ofLS-OCMB for predicting a second relapse was 2.50 (95% CI 1.72–3.64, p < 0.001). The risk of reaching EDSS scores of 4 and 6 and SPMS was significantly higher among patients with LSOCMB (aHR 2.96, 95% CI 1.54–5.71, p = 0.001; aHR 4.96, 95% CI 2.22–11.07, p < 0.001; and aHR 2.31, 95% CI 1.08–4.93, p = 0.03, respectively).Conclusions: ITMS predicts an aggressive MS at disease onset, especially when detected as LS-OCMB.Classification of Evidence: This study provides Class II evidence that lipid-specific IgM oligoclonal bands can predict progression from CIS to MS and a worse disease course over a follow-up of at least 2 years",

author = "Enric Monreal and {Sainz de la Maza}, Susana and Lucienne Costa-Frossard and Paulette Walo-Delgado and Javier Zamora and Fernandez-Velasco, {Jose Ignacio} and Noelia Villarrubia and Mercedes Espi{\~n}o and Daniel Lourido and Paloma Lapuente and Inmaculada Toboso and Alvarez-Cerme{\~n}o, {Jose Carlos} and Jaime Masjuan and Villar, {Luisa Marıa}",

year = "2021",

month = jul,

day = "22",

doi = "10.1212/NXI.0000000000001047",

language = "English",

volume = "8",

journal = "Neurology: Neuroimmunology and NeuroInflammation",

issn = "2332-7812",

publisher = "Lippincott Williams and Wilkins",

number = "5",

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Monreal, E, Sainz de la Maza, S, Costa-Frossard, L, Walo-Delgado, P, Zamora, J, Fernandez-Velasco, JI, Villarrubia, N, Espiño, M, Lourido, D, Lapuente, P, Toboso, I, Alvarez-Cermeño, JC, Masjuan, J & Villar, LM 2021, 'Predicting aggressive multiple sclerosis with intrathecal IgM synthesis among patients with a clinically isolated syndrome', Neurology: Neuroimmunology and NeuroInflammation, vol. 8, no. 5, e1047. https://doi.org/10.1212/NXI.0000000000001047

TY - JOUR

T1 - Predicting aggressive multiple sclerosis with intrathecal IgM synthesis among patients with a clinically isolated syndrome

AU - Monreal, Enric

AU - Sainz de la Maza, Susana

AU - Costa-Frossard, Lucienne

AU - Walo-Delgado, Paulette

AU - Zamora, Javier

AU - Fernandez-Velasco, Jose Ignacio

AU - Villarrubia, Noelia

AU - Espiño, Mercedes

AU - Lourido, Daniel

AU - Lapuente, Paloma

AU - Toboso, Inmaculada

AU - Alvarez-Cermeño, Jose Carlos

AU - Masjuan, Jaime

AU - Villar, Luisa Marıa

PY - 2021/7/22

Y1 - 2021/7/22

N2 - Objective: To determine the best method to measure intrathecal immunoglobulin (Ig) M synthesis(ITMS), a biomarker of worse prognosis in multiple sclerosis (MS). We compared the ability for predicting a poor evolution of 4 methods assessing ITMS (IgM oligoclonal bands[OCMBs], lipid-specific OCMBs [LS-OCMBs], Reibergram, and IgM index) in patients with aclinically isolated syndrome (CIS).Methods: Prospective study with consecutive patients performed at a referral MS center. We used unadjusted and multivariate Cox regressions for predicting a second relapse, Expanded Disability Status Scale (EDSS) scores of 4 and 6, and development of secondary progressive MS(SPMS).Results: A total of 193 patients were included, with a median (interquartile range) age of 31 (25–38) years and a median follow-up of 12.9 years. Among all methods, only OCMB, LS-OCMB, and Reibergram significantly identified patients at risk of some of the pre-established outcomes,being LS-OCMB the technique with the strongest associations. Adjusted hazard ratio (aHR) ofLS-OCMB for predicting a second relapse was 2.50 (95% CI 1.72–3.64, p < 0.001). The risk of reaching EDSS scores of 4 and 6 and SPMS was significantly higher among patients with LSOCMB (aHR 2.96, 95% CI 1.54–5.71, p = 0.001; aHR 4.96, 95% CI 2.22–11.07, p < 0.001; and aHR 2.31, 95% CI 1.08–4.93, p = 0.03, respectively).Conclusions: ITMS predicts an aggressive MS at disease onset, especially when detected as LS-OCMB.Classification of Evidence: This study provides Class II evidence that lipid-specific IgM oligoclonal bands can predict progression from CIS to MS and a worse disease course over a follow-up of at least 2 years

AB - Objective: To determine the best method to measure intrathecal immunoglobulin (Ig) M synthesis(ITMS), a biomarker of worse prognosis in multiple sclerosis (MS). We compared the ability for predicting a poor evolution of 4 methods assessing ITMS (IgM oligoclonal bands[OCMBs], lipid-specific OCMBs [LS-OCMBs], Reibergram, and IgM index) in patients with aclinically isolated syndrome (CIS).Methods: Prospective study with consecutive patients performed at a referral MS center. We used unadjusted and multivariate Cox regressions for predicting a second relapse, Expanded Disability Status Scale (EDSS) scores of 4 and 6, and development of secondary progressive MS(SPMS).Results: A total of 193 patients were included, with a median (interquartile range) age of 31 (25–38) years and a median follow-up of 12.9 years. Among all methods, only OCMB, LS-OCMB, and Reibergram significantly identified patients at risk of some of the pre-established outcomes,being LS-OCMB the technique with the strongest associations. Adjusted hazard ratio (aHR) ofLS-OCMB for predicting a second relapse was 2.50 (95% CI 1.72–3.64, p < 0.001). The risk of reaching EDSS scores of 4 and 6 and SPMS was significantly higher among patients with LSOCMB (aHR 2.96, 95% CI 1.54–5.71, p = 0.001; aHR 4.96, 95% CI 2.22–11.07, p < 0.001; and aHR 2.31, 95% CI 1.08–4.93, p = 0.03, respectively).Conclusions: ITMS predicts an aggressive MS at disease onset, especially when detected as LS-OCMB.Classification of Evidence: This study provides Class II evidence that lipid-specific IgM oligoclonal bands can predict progression from CIS to MS and a worse disease course over a follow-up of at least 2 years

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U2 - 10.1212/NXI.0000000000001047

DO - 10.1212/NXI.0000000000001047

M3 - Article

SN - 2332-7812

VL - 8

JO - Neurology: Neuroimmunology and NeuroInflammation

JF - Neurology: Neuroimmunology and NeuroInflammation

IS - 5

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Predicting aggressive multiple sclerosis with intrathecal IgM synthesis among patients with a clinically isolated syndrome

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