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

Stauch, Chris; Reiber, Hansotto; Rauchenzauner, Markus; Strasak, Alexander; Pohl, Daniela; Hanefeld, F.; Gärtner, Jutta; Rostásy, K.

doi:10.1177/1352458510388543

Cited by 33 publications

(36 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Analysis of CSF IgM was also assessed by the German group, and showed the presence of intrathecal IgM synthesis in 44 (62%) of 70 children. 88 The absence of CSF IgM was associated with an increased relapse rate, particularly in the first 2 years of disease, and especially in girls. These findings have not yet been replicated in subsequent cohorts and seem to differ from findings regarding CSF IgM in adults.…”

Section: Pathobiological Insightsmentioning

confidence: 97%

Multiple sclerosis in children: an update on clinical diagnosis, therapeutic strategies, and research

Waldman¹,

Ghezzi²,

Bar‐Or³

et al. 2014

The Lancet Neurology

136

119

View full text Add to dashboard Cite

The clinical features, diagnostic challenges, neuroimaging appearance, therapeutic options, and pathobiological research progress in childhood—and adolescent—onset multiple sclerosis have been informed by many new insights in the past 7 years. National programmes in several countries, collaborative research efforts, and an established international paediatric multiple sclerosis study group have contributed to revised clinical diagnostic definitions, identified clinical features of multiple sclerosis that differ by age of onset, and made recommendations regarding the treatment of paediatric multiple sclerosis. The relative risks conveyed by genetic and environmental factors to paediatric multiple sclerosis have been the subject of several large cohort studies. MRI features have been characterised in terms of qualitative descriptions of lesion distribution and applicability of MRI aspects to multiple sclerosis diagnostic criteria, and quantitative studies have assessed total lesion burden and the effect of the disease on global and regional brain volume. Humoral-based and cell-based assays have identified antibodies against myelin, potassium-channel proteins, and T-cell profiles that support an adult-like T-cell repertoire and cellular reactivity against myelin in paediatric patients with multiple sclerosis. Finally, the safety and efficacy of standard first-line therapies in paediatric multiple sclerosis populations are now appreciated in more detail, and consensus views on the future conduct and feasibility of phase 3 trials for new drugs have been proposed.

show abstract

Section: Pathobiological Insightsmentioning

confidence: 97%

Multiple sclerosis in children: an update on clinical diagnosis, therapeutic strategies, and research

Waldman¹,

Ghezzi²,

Bar‐Or³

et al. 2014

The Lancet Neurology

136

119

View full text Add to dashboard Cite

show abstract

“…22 CSF IgM OCBs can also be found in a subset of patients with pediatric-and adult-onset MS. In adults their presence has been associated with more active/ aggressive disease, 23 but such an association has not been established in pediatric MS. 24 Of note, CSF exhibits age-related changes independent of MS disease mechanisms, particularly around puberty. Reiber et al 20 showed that the amount of intrathecal IgG doubles during puberty because of an increase in the albumin quotient, which represents normal physiologic growth.…”

Section: General Aspects Of Cns Inflammatory Demyelinating Diseases Mmentioning

confidence: 99%

Immunopathophysiology of pediatric CNS inflammatory demyelinating diseases

et al. 2016

View full text Add to dashboard Cite

Elucidating pathophysiologic mechanisms underlying the spectrum of pediatric-onset CNS demyelinating diseases, particularly those that may distinguish multiple sclerosis (MS) from other entities, promises to both improve diagnostics and guide more-informed therapeutic decisions. Observations that pediatric-and adult-onset MS share the same genetic and environmental risk factors support the view that these conditions represent essentially the same illness manifesting at different ages. Nonetheless, special consideration must be given when CNS inflammation manifests in early life, at a time when multiple organs (including immune and nervous systems) are actively maturing. CSF analysis in pediatric-onset MS points to chronic CNS inflammation, supported by observations from limited pathologic material available for study. Emerging results implicate abnormalities in both effector and regulatory T cell subsets, and potentially immune senescence, in children with MS. Although CNS-directed antibodies (including antibodies recognizing myelin antigens; Kir4.1) can be documented in pediatric-onset MS, their pathophysiologic significance (as in adults) remains unclear. This is in contrast to the presence of serum and/or CSF antibodies recognizing aquaporin-4, which, when measured using validated cell-based assays, supports the diagnosis of a neuromyelitis optica spectrum disorder, distinct from MS. Presence of anti-myelin oligodendrocyte glycoprotein antibodies documented with similar cell-based assays may also be associated with pathophysiologically distinct disease phenotypes in children. The substantial impact of pediatriconset MS on normal brain development and function underscores the importance of elucidating both the immunobiology and neurobiology of disease. Ongoing efforts are aimed at developing and validating biological measures that define pathophysiologically distinct monophasic and chronic forms of pediatric CNS demyelination. Neurology ® 2016;87 (Suppl 2):S12-S19 GLOSSARY ADEM 5 acute disseminated encephalomyelitis; AQP4 5 aquaporin-4; BBB 5 blood-brain barrier; CBA 5 cell-based assay; EDSS 5 Expanded Disability Status Scale; MBP 5 myelin basic protein; MOG 5 myelin oligodendrocyte glycoprotein; MS 5 multiple sclerosis; NMO 5 neuromyelitis optica; NMOSD 5 NMO spectrum disorder; OCB 5 oligoclonal band; ON 5 optic neuritis; OPC 5 oligodendrocyte precursor cell; TM 5 transverse myelitis.There is presently limited insight into the pathophysiologic mechanisms underlying childhoodonset inflammatory demyelinating diseases. Because these disorders occur in the context of the developing immune and nervous systems, understanding the implications to both disease mechanisms and efficacy and safety profiles of potential therapeutics will help guide optimal management approaches for these children and adolescents. Elucidating the biology of pediatric-onset multiple sclerosis (MS) may provide key insights into earliest targets and processes involved in disease pathogenesis as well as into the broader spectrum of CNS...

show abstract

“…For the comparison of groups we introduced now a less specific but more sensitive reference range for Q mean AE 2 SD (still including 96% of the controls in the reference range) ( Figure 2). This allowed the integration of young children with a weaker intrathecal IgM response in the statistical comparison of age-related variations in MS. 3,4 As shown in Figure 2 of Stauch et al 4 for the method comparison between qualitative and quantitative IgM results, three of the IgM quotients measured by Villar et al are around or below the mean Q IgM of the controls, i.e. they have a very high probability to be normal or to be without an intrathecal IgM synthesis.…”

mentioning

confidence: 97%

“…Reference range of IgG quotients based on a Q mean AE 3 SD (diagnostic application) and with Q mean AE 2 SD (statistic application). [3][4][5] …”

mentioning

confidence: 98%

“…In the range of a weak intrathecal response, often in the range of the upper reference limit (Q lim in Figure 2), but we detected them not in the range of or below Q mean (IgG) in thousands of samples analysed. 4 ) is demonstrated in the quotient diagram with calculated 20% intrathecal IgM synthesis, clearly above the reference range and thus has a statistical probability of >99.5% to be not normal in contrast to the qualitative analysis. However, in this case an analytical imprecision in immunochemical nephelometry could be considered as an alternative to explain the discrepancy.…”

mentioning

confidence: 98%

See 1 more Smart Citation

Response to the letter of Villar et al. ‘Quantitative and qualitative IgM analysis in CSF’

Reiber

Rostásy²

2011

Mult Scler

View full text Add to dashboard Cite

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

Cited by 33 publications

References 21 publications

Multiple sclerosis in children: an update on clinical diagnosis, therapeutic strategies, and research

Multiple sclerosis in children: an update on clinical diagnosis, therapeutic strategies, and research

Immunopathophysiology of pediatric CNS inflammatory demyelinating diseases

Response to the letter of Villar et al. ‘Quantitative and qualitative IgM analysis in CSF’

Contact Info

Product

Resources

About