Titre
Intrathecal Immunoglobulin M Synthesis is an Independent Biomarker for Higher Disease Activity and Severity in Multiple Sclerosis.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Oechtering, J.
Auteure/Auteur
Schaedelin, S.
Auteure/Auteur
Benkert, P.
Auteure/Auteur
Müller, S.
Auteure/Auteur
Achtnichts, L.
Auteure/Auteur
Vehoff, J.
Auteure/Auteur
Disanto, G.
Auteure/Auteur
Findling, O.
Auteure/Auteur
Fischer-Barnicol, B.
Auteure/Auteur
Orleth, A.
Auteure/Auteur
Chan, A.
Auteure/Auteur
Pot, C.
Auteure/Auteur
Barakovic, M.
Auteure/Auteur
Rahmanzadeh, R.
Auteure/Auteur
Galbusera, R.
Auteure/Auteur
Heijnen, I.
Auteure/Auteur
Lalive, P.H.
Auteure/Auteur
Wuerfel, J.
Auteure/Auteur
Subramaniam, S.
Auteure/Auteur
Aeschbacher, S.
Auteure/Auteur
Conen, D.
Auteure/Auteur
Naegelin, Y.
Auteure/Auteur
Maceski, A.
Auteure/Auteur
Meier, S.
Auteure/Auteur
Berger, K.
Auteure/Auteur
Wiendl, H.
Auteure/Auteur
Lincke, T.
Auteure/Auteur
Lieb, J.
Auteure/Auteur
Yaldizli, Ö.
Auteure/Auteur
Sinnecker, T.
Auteure/Auteur
Derfuss, T.
Auteure/Auteur
Regeniter, A.
Auteure/Auteur
Zecca, C.
Auteure/Auteur
Gobbi, C.
Auteure/Auteur
Kappos, L.
Auteure/Auteur
Granziera, C.
Auteure/Auteur
Leppert, D.
Auteure/Auteur
Kuhle, J.
Auteure/Auteur
Groupes de travail
and for the Swiss Multiple Sclerosis Cohort Study
Liens vers les personnes
Liens vers les unités
ISSN
1531-8249
Statut éditorial
Publié
Date de publication
2021-09
Volume
90
Numéro
3
Première page
477
Dernière page/numéro d’article
489
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Publication Status: ppublish
Résumé
We aimed to determine in relapsing multiple sclerosis (MS) whether intrathecal synthesis of immunoglobulin (Ig) M and IgG is associated with outcomes reflecting inflammatory activity and chronic worsening.
We compared cerebrospinal fluid analysis, clinical and magnetic resonance imaging data, and serum neurofilament light chain (sNfL) levels at baseline and follow-up in 530 patients with relapsing MS. Patients were categorized by the presence of oligoclonal IgG bands (OCGB) and intrathecal synthesis of IgG and IgM (intrathecal fraction [IF]: IgG <sub>IF</sub> and IgM <sub>IF</sub> ). Relationships with the time to first relapse, sNfL concentrations, T2-weighted (T2w) lesions, MS Severity Score (MSSS), and time to initiation of high-efficacy therapy were analyzed in covariate-adjusted statistical models.
By categorical analysis, in patients with IgM <sub>IF</sub> the median time to first relapse was 28 months shorter and MSSS on average higher by 1.11 steps compared with patients without intrathecal immunoglobulin synthesis. Moreover, patients with IgM <sub>IF</sub> had higher sNfL concentrations, more new/enlarging T2w lesions, and higher total T2w lesion counts (all p ≤ 0.01). These associations were absent or equally smaller in patients who were positive for only OCGB or OCGB/IgG <sub>IF</sub> . Furthermore, quantitative analyses revealed that in patients with IgM <sub>IF</sub> ≥ median, the time to first relapse and to initiation of high-efficacy therapy was shorter by 32 and by 203 months, respectively (both p < 0.01), in comparison to patients with IgM <sub>IF</sub> < median. Dose-dependent associations were also found for IgM <sub>IF</sub> but not for IgG <sub>IF</sub> with magnetic resonance imaging-defined disease activity and sNfL.
This large study supports the value of intrathecal IgM synthesis as an independent biomarker of disease activity and severity in relapsing MS. ANN NEUROL 2021;90:477-489.
We compared cerebrospinal fluid analysis, clinical and magnetic resonance imaging data, and serum neurofilament light chain (sNfL) levels at baseline and follow-up in 530 patients with relapsing MS. Patients were categorized by the presence of oligoclonal IgG bands (OCGB) and intrathecal synthesis of IgG and IgM (intrathecal fraction [IF]: IgG <sub>IF</sub> and IgM <sub>IF</sub> ). Relationships with the time to first relapse, sNfL concentrations, T2-weighted (T2w) lesions, MS Severity Score (MSSS), and time to initiation of high-efficacy therapy were analyzed in covariate-adjusted statistical models.
By categorical analysis, in patients with IgM <sub>IF</sub> the median time to first relapse was 28 months shorter and MSSS on average higher by 1.11 steps compared with patients without intrathecal immunoglobulin synthesis. Moreover, patients with IgM <sub>IF</sub> had higher sNfL concentrations, more new/enlarging T2w lesions, and higher total T2w lesion counts (all p ≤ 0.01). These associations were absent or equally smaller in patients who were positive for only OCGB or OCGB/IgG <sub>IF</sub> . Furthermore, quantitative analyses revealed that in patients with IgM <sub>IF</sub> ≥ median, the time to first relapse and to initiation of high-efficacy therapy was shorter by 32 and by 203 months, respectively (both p < 0.01), in comparison to patients with IgM <sub>IF</sub> < median. Dose-dependent associations were also found for IgM <sub>IF</sub> but not for IgG <sub>IF</sub> with magnetic resonance imaging-defined disease activity and sNfL.
This large study supports the value of intrathecal IgM synthesis as an independent biomarker of disease activity and severity in relapsing MS. ANN NEUROL 2021;90:477-489.
PID Serval
serval:BIB_D94F4A25CF2E
PMID
Open Access
Oui
Date de création
2021-06-14T12:51:36.106Z
Date de création dans IRIS
2025-05-21T04:05:47Z
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34057235_BIB_D94F4A25CF2E.pdf
Version du manuscrit
published
Licence
https://creativecommons.org/licenses/by-nc/4.0
Taille
1.09 MB
Format
Adobe PDF
PID Serval
serval:BIB_D94F4A25CF2E.P001
URN
urn:nbn:ch:serval-BIB_D94F4A25CF2E6
Somme de contrôle
(MD5):a0efae71b6769ea41c41d0ab1d99769a