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Updated: Jun 6, 2026

Quantitative Measurement of Intrathecally Synthesized Proteins in Mice
Published on: November 29, 2019
Intrathecal IgM synthesis in pediatric MS is not a negative prognostic marker of disease progression: quantitative
C Stauch1, H Reiber, M Rauchenzauner
1Department of Pediatrics and Pediatric Neurology, Georg-August University Göttingen, Germany.
Background:
Intrathecal IgM synthesis is reported to be associated with a worse prognosis in adults with multiple sclerosis (MS).
Objective:
To study the predictive value of intrathecal IgM synthesis for the clinical course of pediatric MS.
Methods:
Seventy children with onset of MS before the age of 16 years and followed for a median period of 10.4 years (range: 0.4-22.8 years) were studied. The two subgroups with (n=44) or without (n=26) intrathecal IgM synthesis were distinguished by a new, very sensitive, evaluation of quantitative analysis in cerebrospinal fluid (CSF)/serum quotient diagrams (Reibergrams). The clinical course and EDSS (Expanded Disability Status Scale) scores at five and ten years were compared with IgM frequencies between both groups with a new statistics program for CSF data.
Results:
The cohort of children without intrathecal IgM production had higher numbers of attacks in the first two years and shorter time intervals between first and second attack, although this was not statistically significant (p=0.04, p=0.15 respectively). In addition there was also a trend for girls without intrathecal IgM synthesis to have a higher EDSS score after 10 years compared with the group with IgM synthesis.
Conclusion:
Intrathecal IgM synthesis is not associated with a more rapid progression of disability in pediatric MS. Reevaluation of data from previous reports about the negative predictive value of intrathecal IgM synthesis in adult MS with a CSF statistics tool show that the apparent contradiction is due to a methodological bias in the qualitative detection of 'oligoclonal' IgM or linear IgM index.
Insights
Intrathecal IgM synthesis does not predict worse outcomes in pediatric multiple sclerosis (MS). New analysis suggests previous adult MS studies had methodological bias in detecting IgM.
Area of Science:
- Pediatric Neurology
- Immunology
- Clinical Research
Background:
- Intrathecal IgM synthesis is linked to poorer prognosis in adult multiple sclerosis (MS).
- The predictive value of intrathecal IgM synthesis in pediatric MS remains unclear.
Purpose of the Study:
- To investigate the prognostic significance of intrathecal IgM synthesis in pediatric MS.
- To compare clinical outcomes in children with and without intrathecal IgM synthesis.
Main Methods:
- Studied 70 children with MS onset before age 16, followed for a median of 10.4 years.
- Utilized sensitive quantitative analysis of cerebrospinal fluid (CSF)/serum quotient diagrams (Reibergrams) to identify intrathecal IgM synthesis.
- Employed a new statistical program for CSF data to compare clinical courses and Expanded Disability Status Scale (EDSS) scores.
Main Results:
- Children without intrathecal IgM synthesis showed a trend towards more attacks in the first two years (p=0.04).
- There was a trend for girls without intrathecal IgM synthesis to have higher EDSS scores after 10 years.
- No statistically significant association was found between intrathecal IgM synthesis and faster disability progression.
Conclusions:
- Intrathecal IgM synthesis is not associated with more rapid disability progression in pediatric MS.
- Methodological bias in qualitative detection of IgM in prior adult MS studies may explain discrepancies.
- Re-evaluation using advanced CSF statistics tools is crucial for accurate interpretation of IgM's role in MS.

