Immunoglobulin M Oligoclonal Bands: Biomarker of Targetable Inflammation in Primary Progressive Multiple Sclerosis

Luisa M. Villar; Bonaventura Casanova; Nadia Ouamara; Manuel Comabella; Farzaneh Jalili; David Leppert; Clara de Andres; Guillermo Izquierdo; Rafael Arroyo; Timucin Avsar; Sergey V. Lapin; Trina Johnson; Xavier Montalban; Oscar Fernandez; Roberto Alvarez-Lafuente; Donna Masterman; Maria I. Garcia-Sanchez; Francisco Coret; Aksel Siva; Evgeniy Evdoshenko; Jose C. Alvarez-Cermeno; Amit Bar-Or

doi:10.1002/ana.24190

Immunoglobulin M Oligoclonal Bands: Biomarker of Targetable Inflammation in Primary Progressive Multiple Sclerosis

Luisa M. Villar, Bonaventura Casanova, Nadia Ouamara, Manuel Comabella, Farzaneh Jalili, David Leppert, Clara de Andres, Guillermo Izquierdo, Rafael Arroyo, Timucin Avsar, Sergey V. Lapin, Trina Johnson, Xavier Montalban, Oscar Fernandez, Roberto Alvarez-Lafuente, Donna Masterman, Maria I. Garcia-Sanchez, Francisco Coret, Aksel Siva, Evgeniy EvdoshenkoJose C. Alvarez-Cermeno, Amit Bar-Or

Department of Medicine

Research output: Contribution to journal › Article › Research › peer-review

49 Citations (Scopus)

Abstract

Objective: To identify a biomarker distinguishing patients who, despite a primary progressive multiple sclerosis (PPMS) clinical course, may nonetheless benefit from immune therapy.Methods: The presence or absence of both immunoglobulin (Ig) G and IgM oligoclonal bands (OCB) was blindly examined in paired cerebrospinal fluid (CSF) and serum samples from a large PPMS patient cohort, and related to clinical and imaging evidence of focal inflammatory disease activity.Results: Using both cross-sectional samples and serial sampling in a subgroup of patients followed prospectively as part of the placebo-controlled OLYMPUS study of rituximab in PPMS, we found that the presence of CSF-restricted IgM OCB (but not of IgG OCB) is associated with an active inflammatory disease phenotype in PPMS patients. This finding was confirmed in an independent, multicenter validation cohort.Interpretation: The presence of CSF IgM OCB may be a biomarker for a subset of PPMS patients with more active inflammatory disease, who may benefit from immune-directed treatments.

Original language	English
Pages (from-to)	231-240
Number of pages	10
Journal	Annals of Neurology
Volume	76
Issue number	2
DOIs	https://doi.org/10.1002/ana.24190
Publication status	Published - Aug 2014

Keywords

Intrathecal igm synthesis
Cerebrospinal-fluid
Disease course
Diagnostic-criteria
Double-blind
Disability
Predicts
Csf
Multicenter
Natalizumab

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Villar, L. M., Casanova, B., Ouamara, N., Comabella, M., Jalili, F., Leppert, D., de Andres, C., Izquierdo, G., Arroyo, R., Avsar, T., Lapin, S. V., Johnson, T., Montalban, X., Fernandez, O., Alvarez-Lafuente, R., Masterman, D., Garcia-Sanchez, M. I., Coret, F., Siva, A., ... Bar-Or, A. (2014). Immunoglobulin M Oligoclonal Bands: Biomarker of Targetable Inflammation in Primary Progressive Multiple Sclerosis. Annals of Neurology, 76(2), 231-240. https://doi.org/10.1002/ana.24190

@article{5ef1d27ac841409ba04044cde09d752f,

title = "Immunoglobulin M Oligoclonal Bands: Biomarker of Targetable Inflammation in Primary Progressive Multiple Sclerosis",

abstract = "Objective: To identify a biomarker distinguishing patients who, despite a primary progressive multiple sclerosis (PPMS) clinical course, may nonetheless benefit from immune therapy.Methods: The presence or absence of both immunoglobulin (Ig) G and IgM oligoclonal bands (OCB) was blindly examined in paired cerebrospinal fluid (CSF) and serum samples from a large PPMS patient cohort, and related to clinical and imaging evidence of focal inflammatory disease activity.Results: Using both cross-sectional samples and serial sampling in a subgroup of patients followed prospectively as part of the placebo-controlled OLYMPUS study of rituximab in PPMS, we found that the presence of CSF-restricted IgM OCB (but not of IgG OCB) is associated with an active inflammatory disease phenotype in PPMS patients. This finding was confirmed in an independent, multicenter validation cohort.Interpretation: The presence of CSF IgM OCB may be a biomarker for a subset of PPMS patients with more active inflammatory disease, who may benefit from immune-directed treatments.",

keywords = "Intrathecal igm synthesis, Cerebrospinal-fluid, Disease course, Diagnostic-criteria, Double-blind, Disability, Predicts, Csf, Multicenter, Natalizumab",

author = "Villar, {Luisa M.} and Bonaventura Casanova and Nadia Ouamara and Manuel Comabella and Farzaneh Jalili and David Leppert and {de Andres}, Clara and Guillermo Izquierdo and Rafael Arroyo and Timucin Avsar and Lapin, {Sergey V.} and Trina Johnson and Xavier Montalban and Oscar Fernandez and Roberto Alvarez-Lafuente and Donna Masterman and Garcia-Sanchez, {Maria I.} and Francisco Coret and Aksel Siva and Evgeniy Evdoshenko and Alvarez-Cermeno, {Jose C.} and Amit Bar-Or",

year = "2014",

month = aug,

doi = "10.1002/ana.24190",

language = "English",

volume = "76",

pages = "231--240",

journal = "Annals of Neurology",

issn = "0364-5134",

publisher = "John Wiley and Sons Inc.",

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Villar, LM, Casanova, B, Ouamara, N, Comabella, M, Jalili, F, Leppert, D, de Andres, C, Izquierdo, G, Arroyo, R, Avsar, T, Lapin, SV, Johnson, T, Montalban, X, Fernandez, O, Alvarez-Lafuente, R, Masterman, D, Garcia-Sanchez, MI, Coret, F, Siva, A, Evdoshenko, E, Alvarez-Cermeno, JC & Bar-Or, A 2014, 'Immunoglobulin M Oligoclonal Bands: Biomarker of Targetable Inflammation in Primary Progressive Multiple Sclerosis', Annals of Neurology, vol. 76, no. 2, pp. 231-240. https://doi.org/10.1002/ana.24190

TY - JOUR

T1 - Immunoglobulin M Oligoclonal Bands

T2 - Biomarker of Targetable Inflammation in Primary Progressive Multiple Sclerosis

AU - Villar, Luisa M.

AU - Casanova, Bonaventura

AU - Ouamara, Nadia

AU - Comabella, Manuel

AU - Jalili, Farzaneh

AU - Leppert, David

AU - de Andres, Clara

AU - Izquierdo, Guillermo

AU - Arroyo, Rafael

AU - Avsar, Timucin

AU - Lapin, Sergey V.

AU - Johnson, Trina

AU - Montalban, Xavier

AU - Fernandez, Oscar

AU - Alvarez-Lafuente, Roberto

AU - Masterman, Donna

AU - Garcia-Sanchez, Maria I.

AU - Coret, Francisco

AU - Siva, Aksel

AU - Evdoshenko, Evgeniy

AU - Alvarez-Cermeno, Jose C.

AU - Bar-Or, Amit

PY - 2014/8

Y1 - 2014/8

N2 - Objective: To identify a biomarker distinguishing patients who, despite a primary progressive multiple sclerosis (PPMS) clinical course, may nonetheless benefit from immune therapy.Methods: The presence or absence of both immunoglobulin (Ig) G and IgM oligoclonal bands (OCB) was blindly examined in paired cerebrospinal fluid (CSF) and serum samples from a large PPMS patient cohort, and related to clinical and imaging evidence of focal inflammatory disease activity.Results: Using both cross-sectional samples and serial sampling in a subgroup of patients followed prospectively as part of the placebo-controlled OLYMPUS study of rituximab in PPMS, we found that the presence of CSF-restricted IgM OCB (but not of IgG OCB) is associated with an active inflammatory disease phenotype in PPMS patients. This finding was confirmed in an independent, multicenter validation cohort.Interpretation: The presence of CSF IgM OCB may be a biomarker for a subset of PPMS patients with more active inflammatory disease, who may benefit from immune-directed treatments.

AB - Objective: To identify a biomarker distinguishing patients who, despite a primary progressive multiple sclerosis (PPMS) clinical course, may nonetheless benefit from immune therapy.Methods: The presence or absence of both immunoglobulin (Ig) G and IgM oligoclonal bands (OCB) was blindly examined in paired cerebrospinal fluid (CSF) and serum samples from a large PPMS patient cohort, and related to clinical and imaging evidence of focal inflammatory disease activity.Results: Using both cross-sectional samples and serial sampling in a subgroup of patients followed prospectively as part of the placebo-controlled OLYMPUS study of rituximab in PPMS, we found that the presence of CSF-restricted IgM OCB (but not of IgG OCB) is associated with an active inflammatory disease phenotype in PPMS patients. This finding was confirmed in an independent, multicenter validation cohort.Interpretation: The presence of CSF IgM OCB may be a biomarker for a subset of PPMS patients with more active inflammatory disease, who may benefit from immune-directed treatments.

KW - Intrathecal igm synthesis

KW - Cerebrospinal-fluid

KW - Disease course

KW - Diagnostic-criteria

KW - Double-blind

KW - Disability

KW - Predicts

KW - Csf

KW - Multicenter

KW - Natalizumab

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U2 - 10.1002/ana.24190

DO - 10.1002/ana.24190

M3 - Article

C2 - 24909126

SN - 0364-5134

VL - 76

SP - 231

EP - 240

JO - Annals of Neurology

JF - Annals of Neurology

IS - 2

ER -

Immunoglobulin M Oligoclonal Bands: Biomarker of Targetable Inflammation in Primary Progressive Multiple Sclerosis

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Keywords

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