Biomarkers and Bioinformatics Poster Presentation

P0097 - Intrathecal immunoglobulin M synthesis is associated with higher serum neurofilament light chain levels and increased MRI disease activity in MS (ID 1089)

Speakers
  • J. Oechtering
Authors
  • J. Oechtering
  • S. Schaedelin
  • P. Benkert
  • M. Barakovic
  • A. Maceski
  • A. Orleth
  • D. Rey
  • T. Sinnecker
  • R. Rahmanzadeh
  • S. Zadic
  • R. Galbusera
  • R. Todea
  • A. Cagol
  • L. Achtnichts
  • S. Aeschbacher
  • K. Berger
  • A. Chan
  • D. Conen
  • T. Derfuss
  • G. Disanto
  • O. Findling
  • B. Fischer-Barnicol
  • I. Heijnen
  • K. Hrusovsky
  • H. Kropshofer
  • P. Lalive
  • J. Lieb
  • T. Lincke
  • J. Lorscheider
  • P. Maggi
  • C. Müller
  • S. Müller
  • Y. Naegelin
  • J. Oksenberg
  • C. Pot
  • R. Du Pasquier
  • E. Radue
  • A. Regeniter
  • A. Salmen
  • J. Vehoff
  • E. Waubant
  • S. Wellmann
  • H. Wiendl
  • J. Würfel
  • Ö. Yaldizli
  • C. Zecca
  • D. Leppert
  • C. Gobbi
  • L. Kappos
  • C. Granziera
  • J. Kuhle
Presentation Number
P0097
Presentation Topic
Biomarkers and Bioinformatics

Abstract

Background

Intrathecal IgM synthesis was reported to be associated with higher clinical disease activity and severity. We found an association also with earlier use of high efficacy treatments in relapsing MS (RMS).

Objectives

To explore whether patients with intrathecal IgM synthesis show a) higher serum neurofilament light chain levels (sNfL) as a reflection of neuronal damage, or b) signs of increased disease severity in cerebral MRI, in patients with RMS followed in the Swiss MS Cohort Study.

Methods

487 patients were categorized by presence of oligoclonal IgG bands (OCGB) and intrathecally produced IgG/M:

1) OCGB-/IgG-/IgM- (reference [ref]);

2) OCGB+/IgG-/IgM-;

3) OCGB+/IgG+/IgM- and

4) OCGB+/IgG+/IgM+.

sNfL was measured (at baseline and every 6- or 12 months) with the NF-light® assay. Age-dependent sNfL z-scores (sNfLz) were modelled in 8865 healthy control samples to reflect the deviation of a patient sNfL value compared to mean values observed in same age healthy controls. Yearly T2 lesion number and occurrence of new/enlarging T2 lesions were automatically assessed in cerebral MRIs and checked manually. Contrast enhancing lesions (CEL) were manually quantified. Linear or negative binomial mixed models were used to investigate the associations between the four CSF Ig patterns and longitudinal sNfLz and MRI measures, adjusted for DMT and other covariates.

Results

IgM+ patients had higher sNfLz vs reference (estimate 0.50 [CI 0.12, 0.89], p=0.011), whereas those with only OCGB+ (0.11 [-0.28, 0.50], p=0.582) or with OCGB+/IgG+ (0.20 [-0.16, 0.56], p=0.270) did not (n=2970 observations). This was confirmed when analyzing only untreated patients adjusting for T2 and CEL numbers (1.16 [0.47, 1.86], p<0.01 vs 0.58 [-0.11, 1.27], p=0.1022 vs 0.51 [-0.11, 1.13], p=0.108 vs ref, respectively) (n=234).

IgM+ patients had 2.28-fold more T2 lesions ([1.51, 3.44], p<0.01) vs ref; for patients with only OCGB+ (1.61 [1.07, 2.43], p=0.0237) or OCGB+/IgG+ (1.58 [CI 1.08, 2.32], p=0.0179) (n=1580) this association was weaker.

IgM+ was associated with a 2.47-fold risk for new/enlarging T2 lesions on yearly follow-up MRIs vs ref (2.47 [1.28, 4.78], p<0.01) but not the two other patient groups (1.84 [CI 0.93; 3.65], p=0.0799 and 1.61 [CI 0.87; 2.95], p=0.1280) (n=861).

Conclusions

Intrathecal IgM synthesis was consistently associated with quantitative measures of neuro-axonal injury and disease severity in RMS. Our findings strongly support the clinical utiliy of this biomarker.

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