Unaltered regulatory B-cell frequency and function in patients with multiple sclerosis

Michel, Laure; Chesneau, Mélanie; Manceau, Philippe; Genty, Athenais; García, Alexandra; Salou, Marion; Ngono, Annie Elong; Pallier, Annaïck; Jacq-Foucher, Marylène; Lefrère, Fabienne; Wiertlewski, Sandrine; Soulillou, Jean‐Paul; Degauque, Nicolas; Laplaud, David‐Axel; Brouard, Sophie

doi:10.1016/j.clim.2014.09.011

Cited by 44 publications

(39 citation statements)

References 52 publications

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“…The relevance of a higher frequency of transitional B cells in the CIS group is less clear. In contrast to results of the current study, transitional B cells have been reported at lower frequency in CIS and relapsing–remitting MS by one group 27 but at similar frequency to HC by another 28 . Shifts within the B‐cell compartment reportedly occur in a temporal relationship with MS disease activity 5 .…”

Section: Discussioncontrasting

confidence: 99%

“…However, we did not detect simultaneously lower frequencies of memory B cells in support of this explanation. Alternatively, increased transitional B cells may indicate a compensatory reaction to inflammation, transitional B cells having been described as regulatory B cells by some studies 28 , 29 . However, as regulatory function of B cells is highly context dependent, functional measures would be required to confirm such a claim here.…”

Section: Discussionmentioning

confidence: 84%

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Altered regulatory T‐cell fractions and Helios expression in clinically isolated syndrome: clues to the development of multiple sclerosis

et al. 2017

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Development of multiple sclerosis (MS) is frequently preceded by an acute or subacute neurological disturbance referred to as clinically isolated syndrome (CIS). The specific immunological disturbances present in CIS remain underexamined. This study analysed peripheral blood mononuclear cells from n=18 treatment-naive individuals with recently diagnosed CIS (<120 days) for disturbances in the phenotype of T regulatory (Treg), follicular T regulatory (Tfr), T helper (Th), follicular T helper (Tfh) and B cells. Relative to healthy controls (n=19), CIS was associated with lower proportions of suppressive CD45RA+FoxP3lo Treg and Tfr cells and greater proportions of non-suppressive CD45RA−FoxP3lo and Th17-like Treg and Tfr. Lower Helios expression (maen fluorescent intensity) was measured across all Treg and Tfr fractions in the CIS group, suggesting less potent regulatory function. Greater frequencies of activated, efficient B-cell helper Tfh subsets and a trend for a higher proportion of IgD−CD27− B cells was also detected in the CIS group, characteristics that were positively correlated with Treg and Tfr Helios expression. These results indicate that Treg and Tfr impairment is an early feature in MS.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 84%

Altered regulatory T‐cell fractions and Helios expression in clinically isolated syndrome: clues to the development of multiple sclerosis

et al. 2017

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“…However, analysis of these B reg in samples from MS patients has yielded conflicting results. Transitional B reg , reported to be numerically and functionally deficient in other autoimmune diseases , were reduced in number in CIS and RRMS patients in one study , whereas a second found no difference between patients and healthy controls . Similarly, the percentage of CD5 + B cells has been associated both inversely and positively with disease progression, while relapse has been associated with both a decrease in the percentage of CD25 + B cells and an increase in FoxP3 + B cells .…”

Section: B Cellsmentioning

confidence: 91%

Circulating immune cells in multiple sclerosis

Jones

Kermode

Lucas

et al. 2016

Clinical and Experimental Immunology

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Summary Circulating T and B lymphocytes contribute to the pathogenesis of the neuroinflammatory autoimmune disease, multiple sclerosis (MS). Further progress in the development of MS treatments is dependent upon a greater understanding of the immunological disturbances that underlie the disease. Analyses of circulating immune cells by flow cytometry have revealed MS‐associated alterations in the composition and function of T and B cell subsets, including temporal changes associated with disease activity. Disturbances in circulating immune populations reflect those observed in the central nervous system and include skewing towards proinflammatory CD4+ and CD8+ T cells and B cells, greater proportions of follicular T helper cells and functional defects in the corresponding T and B regulatory subsets. Utilizing the analytical power of modern flow cytometers, researchers are now well positioned to monitor immunological changes associated with disease activity or intervention, describe immunological signatures with predictive value and identify targets for therapeutic drug development. This review discusses the contribution of various T and B lymphocyte subsets to MS pathogenesis, provides current and relevant phenotypical descriptions to assist in experimental design and highlights areas of future research.

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“…In these reports, a reduction in Bregs generally correlated with more severe disease in patients. In contrast, other investigators have shown normal number and function of Bregs in MS patients [31]. These conflicting data indicate the complex role of Bregs in autoimmune neurological diseases.…”

Section: Role Of B Cells In Autoimmune Neurological Diseasesmentioning

confidence: 86%

Inebilizumab, a B Cell-Depleting Anti-CD19 Antibody for the Treatment of Autoimmune Neurological Diseases: Insights from Preclinical Studies

Chen

Gallagher²,

Monson

et al. 2016

JCM

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Exaggerated or inappropriate responses by B cells are an important feature in many types of autoimmune neurological diseases. The recent success of B-cell depletion in the treatment of multiple sclerosis (MS) has stimulated the development of novel B-cell-targeting therapies with the potential for improved efficacy. CD19 has emerged as a promising target for the depletion of B cells as well as CD19-positive plasmablasts and plasma cells. Inebilizumab (MEDI-551), an anti-CD19 antibody with enhanced antibody-dependent cell-mediated cytotoxicity against B cells, is currently being evaluated in MS and neuromyelitis optica. This review discusses the role of B cells in autoimmune neurological disorders, summarizes the development of inebilizumab, and analyzes the recent results for inebilizumab treatment in an autoimmune encephalitis mouse model. The novel insights obtained from these preclinical studies can potentially guide future investigation of inebilizumab in patients.

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Unaltered regulatory B-cell frequency and function in patients with multiple sclerosis

Cited by 44 publications

References 52 publications

Altered regulatory T‐cell fractions and Helios expression in clinically isolated syndrome: clues to the development of multiple sclerosis

Altered regulatory T‐cell fractions and Helios expression in clinically isolated syndrome: clues to the development of multiple sclerosis

Circulating immune cells in multiple sclerosis

Inebilizumab, a B Cell-Depleting Anti-CD19 Antibody for the Treatment of Autoimmune Neurological Diseases: Insights from Preclinical Studies

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