Searching across hundreds of databases

Our searching services are busy right now. Your search will reload in five seconds.

X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

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

Immunology | 2021

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.

Pubmed ID: 33880776 RIS Download

Associated grants

  • Agency: Biotechnology and Biological Sciences Research Council, United Kingdom
    Id: BB/F008309/1
  • Agency: Wellcome Trust, United Kingdom
    Id: 208938/Z/17/Z
  • Agency: Medical Research Council, United Kingdom
    Id: MC_UU_12014/12
  • Agency: Medical Research Council, United Kingdom
    Id: 2017-18 MM9MC_PC_17167
  • Agency: Medical Research Council, United Kingdom
    Id: MC_UU_12014/8
  • Agency: Wellcome Trust, United Kingdom
  • Agency: Medical Research Council, United Kingdom
    Id: MC_PC_17167

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

This is a list of tools and resources that we have found mentioned in this publication.


FastQC (tool)

RRID:SCR_014583

Quality control software that perform checks on raw sequence data coming from high throughput sequencing pipelines. This software also provides a modular set of analyses which can give a quick impression of the quality of the data prior to further analysis.

View all literature mentions

CellProfiler Image Analysis Software (tool)

RRID:SCR_007358

Software tool to enable biologists without training in computer vision or programming to quantitatively measure phenotypes from thousands of images automatically. It counts cells and also measures the size, shape, intensity and texture of every cell (and every labeled subcellular compartment) in every image. It was designed for high throughput screening but can perform automated image analysis for images from time-lapse movies and low-throughput experiments. CellProfiler has an increasing number of algorithms to identify and measure properties of neuronal cell types.

View all literature mentions

edgeR (tool)

RRID:SCR_012802

Bioconductor software package for Empirical analysis of Digital Gene Expression data in R. Used for differential expression analysis of RNA-seq and digital gene expression data with biological replication.

View all literature mentions

featureCounts (tool)

RRID:SCR_012919

A read summarization program, which counts mapped reads for the genomic features such as genes and exons.

View all literature mentions

Agilent Technologies (tool)

RRID:SCR_013575

Company provides laboratories worldwide with analytical instruments and supplies, clinical and diagnostic testing services, consumables, applications and expertise in life sciences and applied chemical markets.

View all literature mentions

Wako (tool)

RRID:SCR_013651

An Antibody supplier

View all literature mentions

HISAT2 (tool)

RRID:SCR_015530

Graph-based alignment of next generation sequencing reads to a population of genomes.

View all literature mentions

CHO-K1 (tool)

RRID:CVCL_0214

Cell line CHO-K1 is a Spontaneously immortalized cell line with a species of origin Cricetulus griseus (Chinese hamster)

View all literature mentions

C57BL/6J (tool)

RRID:IMSR_JAX:000664

Mus musculus with name C57BL/6J from IMSR.

View all literature mentions