B-Cell Depletion with Rituximab in Relapsing–Remitting Multiple Sclerosis

Hauser, Stephen L.; Waubant, Emmanuelle; Arnold, Douglas L.; Vollmer, Timothy; Antel, Jack P.; Fox, Robert J.; Bar‐Or, Amit; Panzara, Michael A.; Sarkar, Neena; Agarwal, Sunil; Langer‐Gould, Annette; Smith, Craig H.

doi:10.1056/nejmoa0706383

Cited by 2,169 publications

(1,917 citation statements)

References 32 publications

Supporting

Mentioning

1,821

Contrasting

Unclassified

Order By: Relevance

“…Several drugs target CD20 and have been shown through phase II clinical trials to decrease new MS disease activity: rituximab [84][85][86], ocrelizumab [87], and ofatumumab (A. Bar-Or et al, in preparation). The effect of these drugs on Bcell depletion does not appear to affect significantly the abnormal antibodies (IgG), OCB number and pattern, or antibody synthesis rates in the CSF of treated patients [88][89][90].…”

Section: B-cell Depletion In Msmentioning

confidence: 99%

Neuroinflammation: Ways in Which the Immune System Affects the Brain

et al. 2015

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: B-cell Depletion In Msmentioning

confidence: 99%

Neuroinflammation: Ways in Which the Immune System Affects the Brain

et al. 2015

Self Cite

View full text Add to dashboard Cite

show abstract

“…While clinical disease is highly variable between patients with relapsing MS, the clinical course of the disease is surprisingly uniform in patients who have entered the progressive phase. Furthermore, onset of steady disease progression, both in patients with primary or secondary progressive disease, occurs around the same age (age [40][41][42][43][44][45][46][47][48][49][50], irrespective of previous disease severity or course [21,22].…”

Section: Oxidative Damage In Ms Lesionsmentioning

confidence: 99%

The molecular basis of neurodegeneration in multiple sclerosis

2011

View full text Add to dashboard Cite

a b s t r a c tStudies aimed to elucidate the pathogenesis of the disease and to find new therapeutic options for multiple sclerosis (MS) patients heavily rely on experimental autoimmune encephalomyelitis (EAE) as a suitable experimental model. This strategy has been highly successful for the inflammatory component of the disease, but had so far little success in the development of neuroprotective therapies, which are also effective in the progressive stage of the disease. Here we discuss opportunities and limitations of EAE models for MS research and provide an overview on the complex mechanisms leading to demyelination and neurodegeneration in this disease. We suggest that the underlying mechanisms involve adaptive and innate immunity. However, mitochondrial injury, resulting in energy failure, is a key element of neurodegeneration in MS and is apparently driven by radical production in activated microglia.

show abstract

“…The strong therapeutic effect of B‐cell depletion shows that these cells play an essential role in multiple sclerosis (MS) 1. B cells may contribute to disease in several ways, including antigen presentation, cytokine secretion, and antibody production 2.…”

Section: Introductionmentioning

confidence: 99%

Selective intrathecal enrichment of G1m1‐positive B cells in multiple sclerosis

Lossius

Tomescu-Baciu

Holmøy

et al. 2017

Ann Clin Transl Neurol

View full text Add to dashboard Cite

Immunoglobulin gamma (IgG) heavy chain genes are associated with susceptibility to multiple sclerosis (MS) and IgG levels in the cerebrospinal fluid (CSF). However, how these variants are implicated in disease mechanisms remains unknown. Here, we show that proliferating plasmablasts expressing the G1m1 allotype of IgG1 are selectively enriched in CSF of G1m1/G1m3 heterozygous MS patients, whereas plasmablasts expressing either G1m1 or G1m3 are evenly distributed in blood. Moreover, there was a preferential intrathecal synthesis of oligoclonal IgG1 of the G1m1 allotype in heterozygous patients, whereas controls with Lyme neuroborreliosis displayed oligoclonal IgG1 of both allotypes. This points to a disease‐specific mechanism involved in B‐cell establishment within the central nervous system in MS.

show abstract

B-Cell Depletion with Rituximab in Relapsing–Remitting Multiple Sclerosis

Cited by 2,169 publications

References 32 publications

Neuroinflammation: Ways in Which the Immune System Affects the Brain

Neuroinflammation: Ways in Which the Immune System Affects the Brain

The molecular basis of neurodegeneration in multiple sclerosis

Selective intrathecal enrichment of G1m1‐positive B cells in multiple sclerosis

Contact Info

Product

Resources

About