Intrathecal IgM synthesis in pediatric MS is not a negative prognostic marker of disease progression: quantitative versus qualitative IgM analysis

A Strasak,H Reiber,D Pohl,C Stauch,J Gärtner,F Hanefeld,KM Rostásy,M Rauchenzauner

doi:10.1177/1352458510388543

Abstract

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.

Highlights

In multiple sclerosis (MS) intrathecal if QIgM > Qmean (IgM) synthesis occurs in 41% of adult patients and in 55% of pediatric patients with an onset of disease before 16 years.[1]
As reported earlier for this group of children with MS,[1] the complete, neuroimmunological pattern in cerebrospinal fluid (CSF) of a chronic inflammatory CNS disease is already present in pediatric MS at first clinical manifestation, that is, inflammatory signs are not gradually evolving.[1,14]
This is confirmed by the individual time course of intrathecal IgM synthesis in 16 patients in this report where the IgM response remains constant in the individual patient over a long time

Summary

Introduction

In multiple sclerosis (MS) intrathecal IgM synthesis occurs in 41% of adult patients and in 55% of pediatric patients with an onset of disease before 16 years.[1] These data were evaluated with a new sensitive statistics concept, which corrects for age-related dynamics of blood-derived proteins in cerebrospinal fluid (CSF), and indicate that frequency and patterns of the humoral immune response is similar in adult and pediatric MS patients.[1,2,3] The only difference between both MS groups was the quantity of intrathecal IgG and IgM synthesis.[1]. 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. 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

Objectives

Methods

Results

Conclusion