Interferon-beta treated-multiple sclerosis patients exhibit a decreased ratio between immature/transitional B cell subset and plasmablasts

Monteiro, Aílton Rocha; Cruto, Catarina; Rosado, Pedro; Rosado, Luiza; Fonseca, Ana Mafalda; Paiva, Artur

doi:10.1016/j.jneuroim.2018.11.001

Cited by 4 publications

(6 citation statements)

References 27 publications

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“…In IFN-β-treated MS patients, the percentages of naïve and transitional B cells were significantly higher in RRMS than in PMS. These findings are also comparable with previous reports describing an increase in naïve and transitional B cells and a decrease in memory B cells by IFN-β treatment in MS consisting of exclusively or mostly RRMS patients [12–14, 22]. It was also reported that the percentage of naïve T cells tended to decrease and that of memory T cells tended to increase in SPMS compared with RRMS [23].…”

Section: Discussionsupporting

confidence: 91%

Long-term use of interferon-β in multiple sclerosis increases Vδ1−Vδ2−Vγ9− γδ T cells that are associated with a better outcome

Maimaitijiang

Watanabe

Sumii

et al. 2019

J Neuroinflammation

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Background We previously reported that Vδ2+Vγ9+ γδ T cells were significantly decreased in multiple sclerosis (MS) patients without disease-modifying therapies (untreated MS) and were negatively correlated with Expanded Disability Status Scale (EDSS) scores, suggesting protective roles of Vδ2+Vγ9+ γδ T cells. Interferon-β (IFN-β) is one of the first-line disease-modifying drugs for MS. However, no previous studies have reported changes in γδ T cell subsets under IFN-β treatment. Therefore, we aimed to clarify the effects of the long-term usage of IFN-β on γδ T cell subsets in MS patients. Methods Comprehensive flow cytometric immunophenotyping was performed in 35 untreated MS and 21 MS patients on IFN-β for more than 2 years (IFN-β-treated MS) including eight super-responders fulfilling no evidence of disease activity criteria, and 44 healthy controls (HCs). Results The percentages of Vδ2+Vγ9+ cells in γδ T cells were significantly lower in untreated and IFN-β-treated MS patients than in HCs. By contrast, the percentages of Vδ1−Vδ2−Vγ9− cells in γδ T cells were markedly higher in IFN-β-treated MS patients than in HCs and untreated MS patients (both p < 0.001). A significant negative correlation between the percentages of Vδ2+Vγ9+ cells in γδ T cells and EDSS scores was confirmed in untreated MS but not evident in IFN-β-treated MS. Moreover, class-switched memory B cells were decreased in IFN-β-treated MS compared with HCs (p < 0.001) and untreated MS patients (p = 0.006). Interestingly, the percentages of Vδ1−Vδ2−Vγ9− cells in γδ T cells were negatively correlated with class-switched memory B cell percentages in all MS patients (r = − 0.369, p = 0.005), and the percentages of Vδ1−Vδ2−Vγ9− cells in Vδ1−Vδ2− γδ T cells were negatively correlated with EDSS scores only in IFN-β super-responders (r = − 0.976, p < 0.001). Conclusions The present study suggests that long-term usage of IFN-β increases Vδ1−Vδ2−Vγ9− γδ T cells, which are associated with a better outcome, especially in IFN-β super-responders. Thus, increased Vδ1−Vδ2−Vγ9− cells together with decreased class-switched memory B cells may contribute to the suppression of disease activity in MS patients under IFN-β treatment.

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Section: Discussionsupporting

confidence: 91%

Long-term use of interferon-β in multiple sclerosis increases Vδ1−Vδ2−Vγ9− γδ T cells that are associated with a better outcome

Maimaitijiang

Watanabe

Sumii

et al. 2019

J Neuroinflammation

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“…The ratio between immature/transitional B cells and plasmablasts can thus be considered as a potential biomarker between phases of RRMS patients. The remission RRMS patients and the healthy subjects presented a similar ratio, and the relapse RRMS patients present a decreased ratio [66]. According to the new and recent data about the recirculation of B cells in RRMS, it seems that the increase of plasmablasts in circulation of relapsing episodes may be due to a migration of these cells from cervical lymph nodes and/or from B cell aggregates described in the meninges of MS patients to the blood marrow in an attempt to promote the immune response [67].…”

Section: B Lymphocytesmentioning

confidence: 84%

“…In our group publications, one can be find the flow strategy with the description of the antibodies used and the mRNA gene expression studies performed in APCs [25], in T cell subsets [41], in γδ T cells [56] and in B cell subsets [66].…”

Section: Methodsmentioning

confidence: 99%

“…• activated pDCs decreased TLR9 consequently decreases Th1 cell differentiation, reduced pro-inflammatory IL-6, TNF-α, IFNγ secretion, expression of CCR7 and increased IL-10 secretion [23][24][25][26]66] • activated status mDCs trough the expression of HLA-DR and mRNA gene expression of CX3CR1 reducing their migration pattern [25] • pDCs showed reduced expression of the maturation markers CD83 and CD86 molecules and lower secretion of proinflammatory cytokines, including IFN-α, and a decreased ability to stimulate allogeneic T cells in response to maturation stimuli [22,65];…”

Section: Antigen Presenting Cellsmentioning

confidence: 99%

“…the ratio between immature/transitional B cells and plasmablasts decreases in relapse when compared to remission RRMS [66] Table 1.…”

Section: Antigen Presenting Cellsmentioning

confidence: 99%

See 2 more Smart Citations

Peripheral Biomarkers in Multiple Sclerosis Patients Treated with Interferon-Beta

Monteiro¹,

Fonseca²,

Paiva³

2022

COVID-19, Neuroimmunology and Neural Function

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Multiple sclerosis is a relapsing and eventually progressive disorder of the central nervous system that continues to challenge researchers who try to understand the pathogenesis of the disease and prevent its progression. Interferon-beta is the most widely prescribed treatment for MS. Peripheral blood seems to mirror the immunological disturbances that underlie MS, which could represent the migration patterns between periphery and other tissues according to the clinical phase of the disease. Based on this assumption, several studies point to significant alterations in peripheral blood homeostasis of different subpopulations of T cells, like γδ T cells or Th1, Th2 and Th17 functional subsets; of B cells subpopulations; and of innate cells like monocytes and dendritic cells. The main goal of this chapter is to make an in-depth review of the major findings described in the literature that correlate specific alterations on different leukocytes subpopulations with disease status, and which therefore have the potential to constitute a peripheral biomarker of disease progression.

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Alterations in circulating T cell functional subpopulations in interferon-beta treated multiple sclerosis patients: A pilot study

Monteiro

Rosado

et al. 2020

Journal of Neuroimmunology

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Interferon-beta treated-multiple sclerosis patients exhibit a decreased ratio between immature/transitional B cell subset and plasmablasts

Cited by 4 publications

References 27 publications

Long-term use of interferon-β in multiple sclerosis increases Vδ1−Vδ2−Vγ9− γδ T cells that are associated with a better outcome

Long-term use of interferon-β in multiple sclerosis increases Vδ1−Vδ2−Vγ9− γδ T cells that are associated with a better outcome

Peripheral Biomarkers in Multiple Sclerosis Patients Treated with Interferon-Beta

Alterations in circulating T cell functional subpopulations in interferon-beta treated multiple sclerosis patients: A pilot study

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