Rituximab reduces B cells and T cells in cerebrospinal fluid of multiple sclerosis patients

Cross, Anne H.; Stark, Jennifer; Lauber, J.; Ramsbottom, Michael J.; Lyons, Joseph

doi:10.1016/j.jneuroim.2006.06.029

Cited by 408 publications

(339 citation statements)

References 31 publications

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“…However, little is currently known about the immunopathological relevance of focused B cell responses within the CNS compartment in MS, and the target antigens or tissues of antibodies produced by cePC remain to be determined. Such knowledge could provide fundamental insights into the immunological mechanisms underlying one of the most frequent neurological disorders and may provide additional understanding of the beneficial mechanisms mediated by novel therapeutic strategies leading to decreased B lymphocyte counts in the CSF of MS patients [20][21][22].…”

Section: Introductionmentioning

confidence: 99%

Clonally expanded plasma cells in the cerebrospinal fluid of MS patients produce myelin‐specific antibodies

et al. 2008

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Clonally expanded plasma cells (cePC) and their presumed products, oligoclonal immunoglobulin G bands (OCB), are characteristic findings in the cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS). While cePC and OCB strongly suggest an involvement of B cell-dependent immune mechanisms in the pathogenesis of MS, their actual pathological relevance and target antigens remain unknown. To further understand the potential role played by cePC, we generated a panel of monoclonal antibodies (MS-mAb) from CSF-derived cePC from four patients with early or definite MS. Single-cell RT-PCR of correctly paired heavy and light chain immunoglobulin genes from individual cePC ensured the subsequent resurrection of their original antigen specificity. Immunofluorescence stainings of MS lesion tissue with MS-mAb revealed myelin reactivity in the cePC repertoire of all four patients and intracellular filament reactivity in one patient. While myelin staining by MS-mAb was only rarely detectable in non-MS CNS white matter tissue, it was greatly enhanced at the edge of demyelinating lesions in MS brain tissue. Our findings provide conclusive evidence for the presence of an antigen-driven B cell response in the CSF of MS patients directed against epitopes present in areas of myelin degradation.

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Section: Introductionmentioning

confidence: 99%

Clonally expanded plasma cells in the cerebrospinal fluid of MS patients produce myelin‐specific antibodies

et al. 2008

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“…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]. Together with the rapid onset of action, these findings suggest that the benefit of B-cell depletion targets antibody-independent functions of B cells.…”

Section: B-cell Depletion In Msmentioning

confidence: 88%

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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“…The majority of these cells were plasma cells, which are not targeted by Rituximab. In a larger study using Rituximab as an add-on therapy for RRMS patients with suboptimal responses to current treatment, B and T cell numbers were reduced in CSF following treatment, but no significant changes were observed in the number of oligoclonal bands, CSF IgG concentration or disability scores (Cross et al, 2006). No serious complications or infections were observed in any of these trials.…”

Section: Therapeutic Depletion Of B Cells In Ms With Rituximabmentioning

confidence: 95%

Chapter 4 B Cells and Autoantibodies in the Pathogenesis of Multiple Sclerosis and Related Inflammatory Demyelinating Diseases

McLaughlin

Wucherpfennig

2008

Advances in Immunology

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Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS). The mainstream view is that MS is caused by an autoimmune attack of the CNS myelin by myelin-specific CD4 T cells, and this perspective is supported by extensive work in the experimental autoimmune encephalomyelitis (EAE) model of MS as well as immunological and genetic studies in humans. However, it is important to keep in mind that other cell populations of the immune system are also essential in the complex series of events leading to MS, as exemplified by the profound clinical efficacy of B cell depletion with Rituximab. This review discusses the mechanisms by which B cells contribute to the pathogenesis of MS and dissects their role as antigen-presenting cells (APCs) to T cells with matching antigen specificity, the production of proinflammatory cytokines and chemokines, as well as the secretion of autoantibodies that target structures on the myelin sheath and the axon. Mechanistic dissection of the interplay between T cells and B cells in MS may permit the development of B cell based therapies that do not require depletion of this important cell population.

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Rituximab reduces B cells and T cells in cerebrospinal fluid of multiple sclerosis patients

Cited by 408 publications

References 31 publications

Clonally expanded plasma cells in the cerebrospinal fluid of MS patients produce myelin‐specific antibodies

Clonally expanded plasma cells in the cerebrospinal fluid of MS patients produce myelin‐specific antibodies

Neuroinflammation: Ways in Which the Immune System Affects the Brain

Chapter 4 B Cells and Autoantibodies in the Pathogenesis of Multiple Sclerosis and Related Inflammatory Demyelinating Diseases

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