Evidence map›Paper›PMID 37715885›Full record

ArticleNeurology and therapy2023

Natalizumab Treatment of Relapsing Remitting Multiple Sclerosis Has No Long-Term Effects on the Proportion of Circulating Regulatory T Cells.

Radu Tanasescu, Nanci Frakich, I-Jun Chou, Perla Filippini, Giulio Podda, Gao Xin, Ranjithmenon Muraleedharan, Oltita Jerca, David Onion, Cris S Constantinescu

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neurology and therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
2.3field-weighted citation impact, top 12% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed, 9 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 3 institutions in 4 countries.

Radu TanasescuAcademic Unit of Mental Health and Clinical Neuroscience, University of Nottingham, Nottingham, NG7 2UH, UK.
Nanci FrakichAcademic Unit of Mental Health and Clinical Neuroscience, University of Nottingham, Nottingham, NG7 2UH, UK.
I-Jun ChouAcademic Unit of Mental Health and Clinical Neuroscience, University of Nottingham, Nottingham, NG7 2UH, UK.
Perla FilippiniAcademic Unit of Mental Health and Clinical Neuroscience, University of Nottingham, Nottingham, NG7 2UH, UK.
Giulio PoddaAcademic Unit of Mental Health and Clinical Neuroscience, University of Nottingham, Nottingham, NG7 2UH, UK.
Gao XinAcademic Unit of Mental Health and Clinical Neuroscience, University of Nottingham, Nottingham, NG7 2UH, UK.
Ranjithmenon MuraleedharanAcademic Unit of Mental Health and Clinical Neuroscience, University of Nottingham, Nottingham, NG7 2UH, UK.
Oltita JercaAcademic Unit of Mental Health and Clinical Neuroscience, University of Nottingham, Nottingham, NG7 2UH, UK.
David OnionSchool of Life Sciences, University of Nottingham, Nottingham, NG7 2UH, UK.
Cris S ConstantinescuAcademic Unit of Mental Health and Clinical Neuroscience, University of Nottingham, Nottingham, NG7 2UH, UK. cris.constantinescu@nottingham.ac.uk.ORCID http://orcid.org/0000-0003-2066-7585
University of Nottingham · GBNottingham University Hospitals NHS Trust · GBBroad Institute · US

Funding

Medical Research Council MR/T024402/1
6 · The paper itself

Abstract

introductionNatalizumab (NTZ), a monoclonal antibody against the integrin α4β1 (VLA-4) found on activated T cells and B cells, blocks the interaction of this integrin with adhesion molecules of central nervous system (CNS) endothelial cells and lymphocyte migration through the blood-brain barrier, effectively preventing new lesion formation and relapses in multiple sclerosis (MS). Whether NTZ treatment has additional effects on the peripheral immune system cells, and how its actions compare with other MS disease-modifying treatments, have not been extensively investigated. In particular, its effect on the proportions of circulating regulatory T cells (Treg) is unclear.

methodsIn this study, we investigated the effect of NTZ treatment in 12 patients with relapsing MS, at 6 and 12 months after the start of treatment. We evaluated the proportions of regulatory T cells (Treg), defined by flow cytometry as CD4+ CD25++ FoxP3+ cells and CD4+ CD25++ CD127- cells at these intervals. As an exploratory study, we also investigated the NTZ effects on the proportions of bulk T and B lymphocyte populations, and of those expressing novel the markers CD195 (CCR5), CD196 (CCR6), or CD161 (KLRB1), which are involved in MS pathogenesis but have been studied less in the context of MS treatment. The effects of NTZ were compared to those obtained with 11 patients under interferon-beta-1a (IFN-β1a) treatment, and against 9 healthy volunteers.

resultsWe observed a transient increment in the proportion of Treg cells at 6 months, which was not sustained at 12 months. We observed a reduction in the proportion of T cells expressing CD195 (CCR5) and CD161 (KLRB1) subsets of T cells.

conclusionWe conclude that NTZ does not have an effect on the proportion of Treg cells over 1 year, but it may affect the expression of molecules important for some aspects MS pathogenesis, in a manner that is not shared with IFN-β1a.

Indexed as

CCR5Foxp3Multiple sclerosisNatalizumabRegulatory T cells

Identifiers

PMID37715885
PMCPMC10630259
OpenAlexW4386799040

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.