Intrathecal Immunoglobulin M Synthesis is an Independent Biomarker for Higher Disease Activity and Severity in Multiple Sclerosis.

Details

Serval ID
serval:BIB_D94F4A25CF2E
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Intrathecal Immunoglobulin M Synthesis is an Independent Biomarker for Higher Disease Activity and Severity in Multiple Sclerosis.
Journal
Annals of neurology
Author(s)
Oechtering J., Schaedelin S., Benkert P., Müller S., Achtnichts L., Vehoff J., Disanto G., Findling O., Fischer-Barnicol B., Orleth A., Chan A., Pot C., Barakovic M., Rahmanzadeh R., Galbusera R., Heijnen I., Lalive P.H., Wuerfel J., Subramaniam S., Aeschbacher S., Conen D., Naegelin Y., Maceski A., Meier S., Berger K., Wiendl H., Lincke T., Lieb J., Yaldizli Ö., Sinnecker T., Derfuss T., Regeniter A., Zecca C., Gobbi C., Kappos L., Granziera C., Leppert D., Kuhle J.
Working group(s)
and for the Swiss Multiple Sclerosis Cohort Study
ISSN
1531-8249 (Electronic)
ISSN-L
0364-5134
Publication state
Published
Issued date
09/2021
Peer-reviewed
Oui
Volume
90
Number
3
Pages
477-489
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
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.
Pubmed
Web of science
Open Access
Yes
Create date
14/06/2021 14:51
Last modification date
23/10/2021 6:38
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