Evidence map›Paper›PMID 32792006›Full record

ArticleActa neuropathologica communications2020

Lipid-specific IgMs induce antiviral responses in the CNS: implications for progressive multifocal leukoencephalopathy in multiple sclerosis.

Lorna Hayden, Tiia Semenoff, Verena Schultz, Simon F Merz, Katie J Chapple, Moses Rodriguez, Arthur E Warrington, Xiaohong Shi, Clive S McKimmie, Julia M Edgar and 3 more

Open access · goldAbstract read
In one paragraph

Article in Acta neuropathologica communications, 2020. 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
1.0field-weighted citation impact, top 21% 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, 14 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

13 authors at 4 institutions in 2 countries.

Lorna HaydenInstitute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, G12 8TA, UK.
Tiia SemenoffInstitute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, G12 8TA, UK.
Verena SchultzInstitute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, G12 8TA, UK.
Simon F MerzInstitute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, G12 8TA, UK.
Katie J ChappleInstitute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, G12 8TA, UK.
Moses RodriguezDepartments of Neurology and Neurosurgery, Mayo Clinic, Rochester, MN, USA.
Arthur E WarringtonDepartments of Neurology and Neurosurgery, Mayo Clinic, Rochester, MN, USA.
Xiaohong ShiInstitute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, G12 8TA, UK.
Clive S McKimmieVirus Host Interaction Team, Leeds Institute of Medical Research, School of Medicine, Faculty of Medicine and Health, University of Leeds, Leeds, LS9 7TF, UK.
Julia M EdgarInstitute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, G12 8TA, UK.
Katja ThümmlerInstitute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, G12 8TA, UK.
Chris LiningtonInstitute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, G12 8TA, UK.
Marieke PingenInstitute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, G12 8TA, UK. Marieke.Pingen@glasgow.ac.uk.ORCID 0000-0001-5689-9076
University of Glasgow · GBMayo Clinic in Arizona · USUniversity of Leeds · GBWellcome Centre for Molecular Parasitology · GB

Funding

Medical Research Council G1001724Medical Research Council NIRG (G1001724)Medical Research Scotland PhD-1031-2016
6 · The paper itself

Abstract

Progressive multi-focal leukoencephalopathy (PML) is a potentially fatal encephalitis caused by JC polyomavirus (JCV). PML principally affects people with a compromised immune system, such as patients with multiple sclerosis (MS) receiving treatment with natalizumab. However, intrathecal synthesis of lipid-reactive IgM in MS patients is associated with a markedly lower incidence of natalizumab-associated PML compared to those without this antibody repertoire. Here we demonstrate that a subset of lipid-reactive human and murine IgMs induce a functional anti-viral response that inhibits replication of encephalitic Alpha and Orthobunyaviruses in multi-cellular central nervous system cultures. These lipid-specific IgMs trigger microglia to produce IFN-β in a cGAS-STING-dependent manner, which induces an IFN-α/β-receptor 1-dependent antiviral response in glia and neurons. These data identify lipid-reactive IgM as a mediator of anti-viral activity in the nervous system and provide a rational explanation why intrathecal synthesis of lipid-reactive IgM correlates with a reduced incidence of iatrogenic PML in MS.

Indexed as

Multiple SclerosisAnimalsAutoantibodiesAutoantigensHumansImmunocompromised HostImmunoglobulin MImmunologic FactorsLeukoencephalopathy, Progressive MultifocalLipidsMiceMice, Inbred C57BLNatalizumabRatsRats, Sprague-DawleyAutoantibodiesAutoantigensImmunoglobulin MImmunologic FactorsLipidsNatalizumabIgMInterferon stimulated genesJohn Cunningham polyomavirus (JCV)MicrogliaType-I interferonViral encephalitis

Identifiers

PMID32792006
PMCPMC7427287
OpenAlexW3048481675

What OpenQuestion holds

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LicenceCC BY
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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.