Evidence map›Paper›PMID 33880776›Full record

ArticleImmunology2021

Modified recombinant human IgG1-Fc is superior to natural intravenous immunoglobulin at inhibiting immune-mediated demyelination.

Christine Baksmeier, Pat Blundell, Julia Steckel, Verena Schultz, Quan Gu, Ana Da Silva Filipe, Alain Kohl, Chris Linnington, Dongli Lu, Anne Dell and 5 more

Open access · hybridAbstract readComparative Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Immunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.4field-weighted citation impact, top 39% 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

4 citing papers in PubMed, 5 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Review
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

15 authors at 5 institutions in 3 countries.

Christine BaksmeierDepartment of Neurology, Medical Faculty, Heinrich-Heine-University Duesseldorf, Duesseldorf, Germany.
Pat BlundellDepartment of Tropical Disease Biology, Liverpool School of Tropical Medicine, Liverpool, UK.
Julia SteckelDepartment of Neurology, Medical Faculty, Heinrich-Heine-University Duesseldorf, Duesseldorf, Germany.
Verena SchultzInstitute of Infection, Immunity and Inflammation, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
Quan GuInstitute of Infection, Immunity and Inflammation, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
Ana Da Silva FilipeInstitute of Infection, Immunity and Inflammation, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
Alain KohlInstitute of Infection, Immunity and Inflammation, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
Chris LinningtonInstitute of Infection, Immunity and Inflammation, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
Dongli LuDepartment of Life Sciences, Imperial College London, London, UK.
Anne DellDepartment of Life Sciences, Imperial College London, London, UK.
Stuart HaslamDepartment of Life Sciences, Imperial College London, London, UK.
Jiabin WangShanghai Center for Systems Biomedicine, Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Jiao Tong University, Shanghai, China.
Dan CzajkowskyState Key Laboratory for Oncogenes and Related Genes and Bio-ID Center, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.
Norbert GoebelsDepartment of Neurology, Medical Faculty, Heinrich-Heine-University Duesseldorf, Duesseldorf, Germany.
Richard J PleassDepartment of Tropical Disease Biology, Liverpool School of Tropical Medicine, Liverpool, UK.ORCID 0000-0001-7438-8296
University of Glasgow · GBHeinrich Heine University Düsseldorf · DEImperial College London · GBLiverpool School of Tropical Medicine · GBShanghai Jiao Tong University · CN

Funding

Biotechnology and Biological Sciences Research Council BB/F008309/1Medical Research Council 2017-18 MM9MC_PC_17167Medical Research Council MC_PC_17167Medical Research Council MC_UU_12014/12Medical Research Council MC_UU_12014/8Wellcome TrustWellcome Trust 208938/Z/17/Z
6 · The paper itself

Abstract

Intravenous immunoglobulin (IVIG) is an established treatment for numerous autoimmune conditions. Although Fc fragments derived from IVIG have shown efficacy in controlling immune thrombocytopenia in children, the mechanisms of action are unclear and controversial. The aim of this study was to dissect IVIG effector mechanisms using further adapted Fc fragments on demyelination in an ex vivo model of the central nervous system-immune interface. Using organotypic cerebellar slice cultures (OSCs) from transgenic mice, we induced extensive immune-mediated demyelination and oligodendrocyte loss with an antibody specific for myelin oligodendrocyte glycoprotein (MOG) and complement. Protective effects of adapted Fc fragments were assessed by live imaging of green fluorescent protein expression, immunohistochemistry and confocal microscopy. Cysteine- and glycan-adapted Fc fragments protected OSC from demyelination in a dose-dependent manner where equimolar concentrations of either IVIG or control Fc were ineffective. The protective effects of the adapted Fc fragments are partly attributed to interference with complement-mediated oligodendroglia damage. Transcriptome analysis ruled out signatures associated with inflammatory or innate immune responses. Taken together, our findings show that recombinant biomimetics can be made that are at least two hundred-fold more effective than IVIG in controlling demyelination by anti-MOG antibodies.

Indexed as

AnimalsAutoantibodiesCerebellumDemyelinating DiseasesHEK293 CellsHumansImmunoglobulin Fc FragmentsImmunoglobulin GImmunoglobulins, IntravenousMiceMice, Inbred C57BLMyelin-Oligodendrocyte GlycoproteinOligodendrogliaOrgan Culture TechniquesRecombinant Fusion ProteinsAutoantibodiesImmunoglobulin Fc FragmentsImmunoglobulin GImmunoglobulins, IntravenousMyelin-Oligodendrocyte GlycoproteinRecombinant Fusion ProteinsdemyelinationFc monomersFc multimersIgGimmunoglobulinintravenous immunoglobulin

Identifiers

PMID33880776
PMCPMC8358725
OpenAlexW3154793572

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.