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

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

doi:10.1016/j.jneuroim.2019.577113

Cited by 4 publications

(7 citation statements)

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“…[41][42][43] The increased number of Tfh17 and Thf17.1 cells together with the higher Tfh/Tfr cell ratio may reflect a compensatory mechanism in response to the cladribine-induced loss of memory B cells, maintaining a functioning B cell system, consistent with the previously reported unchanged levels of immunoglobulins during cladribine treatment. 29 The effects of several disease-modifying therapies (fingolimod, 44 interferon-beta, 45 abatacept, 46 and dimethyl fumarate 47 ) on circulating Tfh and Tfr cells were previously investigated. These studies showed effects on frequencies and total numbers of Tfh and Tfr cells, but responses varied between treatments, and not all studies discriminated between Tfh and Tfr cells.…”

Section: Discussionmentioning

confidence: 99%

Cladribine Effects on T and B Cells and T Cell Reactivity in Multiple Sclerosis

Hansen

Essen

Mahler

et al. 2023

Annals of Neurology

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ObjectiveCladribine tablet therapy is an efficacious treatment for multiple sclerosis (MS), however, its mechanism of action on T and B cell subsets remains unclear. The purpose of this study was to investigate the treatment effects of cladribine on the peripheral pool of T and B cells subsets and reactivity toward central nervous system (CNS) antigens.MethodsIn this cross‐sectional exploratory study, frequencies and absolute counts of peripheral T and B cell subsets and B cell cytokine production from untreated patients with relapsing–remitting MS (RRMS) and patients treated with cladribine for 1 year were measured using flow cytometry. Autoreactivity was assessed using a FluoroSpot assay.ResultsWe found that 1 year after initiation of cladribine treatment, a lower number of CD4+ T cells was persisting whereas CD19+ B cell counts were normalized compared to untreated patients with RRMS. Follicular helper T cells and their effecter subsets producing cytokines exerting distinct B cell helper activity were lower and, additionally, the peripheral B cell pool was skewed toward a naïve and anti‐inflammatory phenotype. Finally, reactivity to the recently identified CNS‐enriched autoantigen RAS guanyl‐releasing protein 2 (RASGRP2), but not to myelin basic protein and myelin oligodendrocyte glycoprotein, was lower in cladribine‐treated patients.InterpretationTogether, these investigations on T and B cell subsets suggest that cladribine treatment impairs the B–T cell crosstalk and reduces their ability to mediate pathogenic effector functions. This may result in specific reduction of autoreactivity to RASGRP2 which is expressed in B cells and brain tissue. ANN NEUROL 2023

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Section: Discussionmentioning

confidence: 99%

Cladribine Effects on T and B Cells and T Cell Reactivity in Multiple Sclerosis

Hansen

Essen

Mahler

et al. 2023

Annals of Neurology

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“…The enhanced potential of Th17.1 cells to infiltrate the CNS was supported by their predominance in CSF of early MS patients and their preferential transmigration across human brain endothelial layers [42,43]. In remission RRMS patients, it was observed that Th17 and Tc17 cells exhibited a higher degree of Th1 plasticity since there were higher frequencies of those cells simultaneously producing intracellular IL-17 and IL-2 or IFNγ or TNFα [41].…”

Section: Cd4 + and Cd8 + T Cellsmentioning

confidence: 94%

“…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%

“…A recent in vivo study observed an increased frequency of circulating Th17 and Tc17 cells, accompanied by increased serum levels of IL-17 in remission RRMS patients treated with IFN-β [41]. This contradiction underlines the need to clarify the role of the IL-17-producing T cells in RRMS patients.…”

Section: Cd4 + and Cd8 + T Cellsmentioning

confidence: 97%

“…A similar frequency of Tfh cells between RRMS patients and healthy subjects was reported. However, this subset tend to exhibit a more proinflammatory activity, since higher frequencies of TNF-α + Tfh cells have been observed [41]. It is well known that Tfh cells play an important role in T/B interactions in germinal centres (GC) and one potential mechanism through which Tfh cells can contribute to MS is in promoting inflammatory B-cell activities [49].…”

Section: Cd4 + and Cd8 + T 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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