B cell-targeted therapy with rituximab and autoimmune neuromuscular disorders

Stübgen, Joerg‐Patrick

doi:10.1016/j.jneuroim.2008.07.019

Cited by 26 publications

(14 citation statements)

References 135 publications

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“…This finding is in contrast to immune therapy by rituximab where the responsiveness was associated with B cell IL-10 production [34]. Considering the substantial progress in B cell targeting therapy approaches regarding MG in recent years [41][42][43], the role of naïve or memory B cells and dysregulation of B cell cytokines on disease development or subgroup specific differences warrants further investigation.…”

Section: Discussionmentioning

confidence: 88%

B cells produce less IL-10, IL-6 and TNF-αin myasthenia gravis

et al. 2014

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B cells from myasthenia gravis (MG) patients with autoantibodies (Aab) against acetylcholine receptor (AChR), muscle-specific kinase (MuSK) or with no detectable Aab were investigated as cytokine producing cells in this study. B cells were evaluated for memory phenotypes and expressions of IL-10, IL-6 and IL-12A. Induced productions of IL-10, IL-6, IL-12p40, TNF-α and LT from isolated B cells in vitro were measured by immunoassays. MG patients receiving immunosuppressive treatment had higher proportions of memory B cells compared with healthy controls and untreated patients. With CD40 stimulation MG patients produced significantly lower levels of IL-10, IL-6. With CD40 and B cell receptor stimulation of B cells, TNF-α production also decreased in addition to these cytokines. The lower levels of these cytokine productions were not related to treatment. Our results confirm a disturbance of B cell subpopulations in MG subgroups on immunosuppressive treatment. B cell derived IL-10, IL-6 and TNF-α are down-regulated in MG, irrespective of different antibody productions. Ineffective cytokine production by B cells may be a susceptibility factor in dysregulation of autoimmune Aab production.

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Section: Discussionmentioning

confidence: 88%

B cells produce less IL-10, IL-6 and TNF-αin myasthenia gravis

et al. 2014

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“…In fact, rituximab, a B-cell-depleting mAb, has been successfully used to treat MG (26-28). Because AChR is a T-cell-dependent antigen, inhibiting T-cell responses should also be effective.…”

Section: Discussionmentioning

confidence: 99%

Myeloid-Derived Suppressor Cells as a Potential Therapy for Experimental Autoimmune Myasthenia Gravis

Shen

et al. 2014

The Journal of Immunology

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We recently demonstrated that hepatic stellate cells induce the differentiation of myeloid-derived suppressor cells (MDSCs) from myeloid progenitors. In this study, we found that adoptive transfer of these MDSCs effectively reversed disease progression in experimental autoimmune myasthenia gravis (EAMG), a T-cell-dependent and B-cell-mediated model for myasthenia gravis. In addition to ameliorated disease severity, MDSC-treated EAMG mice showed suppressed acetylcholine receptors (AChR)-specific T-cell responses, decreased levels of serum anti-AChR IgGs, and reduced complement activation at the neuromuscular junctions. Incubating MDSCs with B cells activated by anti-IgM or anti-CD40 antibodies inhibited the proliferation of these in vitro activated B cells. Administering MDSCs into mice immunized with a T-cell-independent antigen inhibited the antigen-specific antibody production in vivo. MDSCs directly inhibit B cells through multiple mechanisms including prostaglandin E2, inducible nitric oxide synthase and arginase. Interestingly, MDSC treatment in EMAG mice does not appear to significantly inhibit their immune response to a non-relevant antigen, ovalbumin. These results demonstrated that hepatic stellate cell-induced MDSCs concurrently suppress both T- and B- cell autoimmunity, leading to effective treatment of established EAMG; and that the MDSCs inhibit AChR-specific immune responses at least partially in an antigen-specific manner. These data suggest that MDSCs could be further developed as a novel approach to treating myasthenia gravis and, even more broadly, other diseases in which T and B cells are involved in pathogenesis.

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“…The proposed association was based on the temporal sequence of events, a lack of alternative explanations, biological plausibility, and analogy [10], as rituximab treatment has been reported to trigger or exacerbate various autoimmune neuromuscular disorders [11].…”

Section: Discussionmentioning

confidence: 99%

Central nervous system inflammatory demyelination after rituximab therapy for idiopathic thrombocytopenic purpura

Stübgen

2010

Journal of the Neurological Sciences

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B cell-targeted therapy with rituximab and autoimmune neuromuscular disorders

Cited by 26 publications

References 135 publications

B cells produce less IL-10, IL-6 and TNF-αin myasthenia gravis

B cells produce less IL-10, IL-6 and TNF-αin myasthenia gravis

Myeloid-Derived Suppressor Cells as a Potential Therapy for Experimental Autoimmune Myasthenia Gravis

Central nervous system inflammatory demyelination after rituximab therapy for idiopathic thrombocytopenic purpura

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