Dataset Information

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

ABSTRACT:

Objective

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.

Methods

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_IF and IgM_IF ). 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.

Results

By categorical analysis, in patients with IgM_IF 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_IF 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_IF . Furthermore, quantitative analyses revealed that in patients with IgM_IF ≥ 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_IF < median. Dose-dependent associations were also found for IgM_IF but not for IgG_IF with magnetic resonance imaging-defined disease activity and sNfL.

Interpretation

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.

SUBMITTER: Oechtering J

PROVIDER: S-EPMC8518907 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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Publications

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

Oechtering Johanna J Schaedelin Sabine S Benkert Pascal P Müller Stefanie S Achtnichts Lutz L Vehoff Jochen J Disanto Giulio G Findling Oliver O Fischer-Barnicol Bettina B Orleth Annette A Chan Andrew A Pot Caroline C Barakovic Muhamed M Rahmanzadeh Reza R Galbusera Riccardo R Heijnen Ingmar I Lalive Patrice H PH Wuerfel Jens J Subramaniam Suvitha S Aeschbacher Stefanie S Conen David D Naegelin Yvonne Y Maceski Aleksandra A Meier Stephanie S Berger Klaus K Wiendl Heinz H Lincke Therese T Lieb Johanna J Yaldizli Özgür Ö Sinnecker Tim T Derfuss Tobias T Regeniter Axel A Zecca Chiara C Gobbi Claudio C Kappos Ludwig L Granziera Cristina C Leppert David D Kuhle Jens J

Annals of neurology 20210622 3

<h4>Objective</h4>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.<h4>Methods</h4>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 b ...[more]

PMID: 34057235

Similar Datasets

Project description:ImportanceReliable biomarkers associated with disability worsening in multiple sclerosis (MS) are still needed.ObjectiveTo determine a possible association of intrathecal IgG synthesis and early disability worsening as measured by Expanded Disability Status Scale (EDSS) scoring in patients with relapsing-remitting MS or clinically isolated syndrome.Design, setting, and participantsCerebrospinal fluid measurements and clinical data from the observational longitudinal German national multiple sclerosis cohort were analyzed. Patients were recruited between August 2010 and November 2015 from 18 centers. Data analysis was completed from August 2018 to December 2018.ExposurePatients were offered standard immunotherapies per national treatment guidelines.Main outcomes and measuresA possible association between intrathecal IgG synthesis and risk of EDSS worsening 4 years after study inclusion was tested as the primary end point by multivariable binomial regression analysis. Kaplan-Meier analysis with a log-rank test was used to assess the association of intrathecal IgG synthesis with the time to EDSS worsening. Associations between intrathecal IgM or IgA synthesis and other cerebrospinal fluid parameters and EDSS worsening were analyzed as exploratory end points. Data collection began before the hypotheses were formulated.ResultsOf all 1376 patients in the German Competence Network of Multiple Sclerosis cohort, 703 patients were excluded owing to missing cerebrospinal fluid or EDSS data. Of the 673 included patients, 459 (68.2%) were women. The mean (SD) age at baseline was 34 (10) years. Intrathecal IgG synthesis was associated with a higher risk of EDSS worsening after 4 years (odds ratio, 2.02 [95% CI, 1.15-3.58]; P = .01), independent of the occurrence of relapses and disease-modifying therapy. Additionally, intrathecal IgG synthesis was associated with earlier EDSS worsening; 4 years after study entry, worsening occurred in 28.4% (95% CI, 22.7%-34.1%) and 18.1% (95% CI, 12.4%-23.9%) of patients with and without intrathecal IgG synthesis, respectively. No association of other routine cerebrospinal fluid parameters with EDSS worsening was found.Conclusions and relevancePatients with new diagnoses of relapsing-remitting multiple sclerosis or clinically isolated syndrome with intrathecal IgG synthesis had a higher risk of and shorter time to EDSS worsening across a 4-year period of follow-up. Intrathecal IgG synthesis is a potentially useful marker for disability worsening in patients with multiple sclerosis and may be useful for early treatment decisions.

Dataset Information

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

Objective

Methods

Results

Interpretation

Publications

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

Similar Datasets

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