Anti-myelin antibodies modulate clinical expression of childhood multiple sclerosis

O’Connor, Kevin; Lopez-Amaya, C.; Gagné, Donald; Lovato, Laura; Moore-Odom, N.H.; Kennedy, J. S.; Krupp, Lauren; Tenembaum, Sílvia; Ness, J.; Belman, Anita; Boyko, A. N.; Ov, Bykova; Mah, Jean K.; Stoian, Cristina; Waubant, Emmanuelle; Kremenchutzky, Marcelo; Ruggieri, Martino; Bardini, Maria Rita; Rensel, Mary; Hahn, Jin S.; Weinstock‐Guttman, Bianca; Yeh, E. Ann; Farrell, Kevin; Freedman, Mark S.; Iivanainen, Matti; Bhan, Virender; Dilenge, Marie-Emmanuelle; Hancock, Mark A.; Gano, Dawn; Fattahie, R.; Kopel, L.; Fournier, Alyson E.; Moscarello, Mario A.; Banwell, Brenda; Bar‐Or, Amit

doi:10.1016/j.jneuroim.2010.02.019

Cited by 62 publications

(52 citation statements)

References 35 publications

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“…anti-myelin basic protein (mBP) antibodies seem to be present at higher frequencies and to exhibit higher affinities in children (both those with pediatric ms and controls) than in adults. 48,49 overall, children with ms and pediatric controls were indistinguishable with respect to prevalence and binding charac teristics of their circulating anti-mBP antibodies, but those with ms who had higher levels of circulating anti-mBP anti bodies were likely to manifest with more-diffuse multifocal inflammatory Cns presenta tions. 49 this finding suggests that while Cns-directed auto antibodies may be present in children as part of the normal humoral repertoire, their presence in a child who develops Cns inflammation may modulate the clinical expression of disease.…”

Section: Key Pointsmentioning

confidence: 93%

“…48,49 overall, children with ms and pediatric controls were indistinguishable with respect to prevalence and binding charac teristics of their circulating anti-mBP antibodies, but those with ms who had higher levels of circulating anti-mBP anti bodies were likely to manifest with more-diffuse multifocal inflammatory Cns presenta tions. 49 this finding suggests that while Cns-directed auto antibodies may be present in children as part of the normal humoral repertoire, their presence in a child who develops Cns inflammation may modulate the clinical expression of disease. antimyelin oligo dendrocyte glyco protein (moG) antibodies to conformational epitopes, which have been implicated in ms and experimental auto immune encephalo myelitis pathogenesis, have also been described at higher frequencies in pediatric-onset ms and acute disseminated encephalomyelit is cases than in adults with ms. 31,50 especially germane to the immunological considera tions of pediatric ms in the context of emerging therapeutics is the potential impact of these agents on normal thymic maturation and function.…”

Section: Key Pointsmentioning

confidence: 93%

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Therapies for multiple sclerosis: considerations in the pediatric patient

et al. 2011

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Current and emerging therapies for multiple sclerosis (MS) offer promise for improved disease control and long-term clinical outcome. To date, these therapies have been evaluated solely in the context of adult MS. However, onset of MS in children is being increasingly recognized, and recent studies have identified a significant impact of MS onset during childhood on cognitive and physical functioning. Optimization of pediatric MS care requires that promising new therapies be made available to children and adolescents, but also that safety and tolerability and potential influence of therapies on the developing immune and neural networks of pediatric patients be closely considered. We propose care algorithms illustrating models for therapy that detail careful monitoring of pediatric patients with MS, provide definitions for inadequate treatment response and treatment escalation, and foster multinational collaboration in future therapeutic trials.

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Section: Key Pointsmentioning

confidence: 93%

Section: Key Pointsmentioning

confidence: 93%

Therapies for multiple sclerosis: considerations in the pediatric patient

et al. 2011

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“…Circulating anti-CNS antibodies have also been described, and investigations are ongoing to determine the roles of anti-myelin oligodendrocyte glycoprotein and anti-inward rectifier-type potassium channel (KIR4.1) serum antibodies. Overall, contributions of intrathecal antibodies in MS likely vary and may include 1) causing injury or modulating disease expression [83]; 2) occurring as epiphenomenon of B-cell activation (while such antibodies may not be pathogenic, they may still be worthwhile investigating for their potential as biomarkers of disease activity and injury); and 3) having a potential to act beneficially, such as may be the case for anti-Nogo and anti-Lingo antibodies.…”

Section: B Cells In Msmentioning

confidence: 99%

Neuroinflammation: Ways in Which the Immune System Affects the Brain

et al. 2015

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Neuroinflammation is the response of the central nervous system (CNS) to disturbed homeostasis and typifies all neurological diseases. The main reactive components of the CNS include microglial cells and infiltrating myeloid cells, astrocytes, oligodendrocytes, and the blood-brain b a r r i e r , c y t o k i n e s , a n d c y t o k i n e s i g n a l i n g . Neuroinflammatory responses may be helpful or harmful, as mechanisms associated with neuroinflammation are involved in normal brain development, as well as in neuropathological processes. This review examines the roles of various cell types that contribute to the immune dysregulation associated with neuroinflammation. Microglia enter the CNS very early in embryonic development and, as such, play an essential role in both the healthy and diseased brain. B-cell diversity contributes to CNS disease through both antibody-dependent and antibody-independent mechanisms. The influences of these B-cell mechanisms on other cell types, including myeloid cells and T cells, are reviewed in relationship to antibody-mediated CNS disorders, paraneoplastic neurological diseases, and multiple sclerosis. New insights into neuroinflammation offer exciting opportunities to investigate potential therapeutic targets for debilitating CNS diseases.

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“…94–99 In a study of children with multiple sclerosis (25 of whom had paired serum and CSF samples) and 106 age-matched controls, 99 immunoblot analysis identified antibodies directed against both mature and immature myelin basic protein (MBP) in 22 (24%) of 91 patients with paediatric multiple sclerosis with a similar frequency (20%) in the controls. In the same study, some of the children with serum MBP antibodies also had anti-MBP antibodies in their CSF.…”

Section: Pathobiological Insightsmentioning

confidence: 99%

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

Waldman¹,

Ghezzi²,

Bar‐Or³

et al. 2014

The Lancet Neurology

132

119

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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.

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Anti-myelin antibodies modulate clinical expression of childhood multiple sclerosis

Cited by 62 publications

References 35 publications

Therapies for multiple sclerosis: considerations in the pediatric patient

Therapies for multiple sclerosis: considerations in the pediatric patient

Neuroinflammation: Ways in Which the Immune System Affects the Brain

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

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