Autoantibodies against the Immunoglobulin-Binding Region of Ro52 Link its Autoantigenicity with Pathogen Neutralization View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-12

AUTHORS

Peter D. Burbelo, Leyla Y. Teos, Jesse L. Herche, Michael J. Iadarola, Ilias Alevizos

ABSTRACT

Ro52/TRIM21 plays a key role in antibody-dependent pathogen neutralization and is a major autoantigen in systemic lupus erythematosus, Sjögren's syndrome (SS), and other autoimmune diseases. Here we evaluated immunoreactivity against Ro52-related molecules in SS and healthy volunteers. Although most proteins examined were not antigenic, several TRIM paralogs, including TRIM22, and TRIM38, showed sporadic immunoreactivity in SS. In contrast, the murine Ro52 ortholog with limited linear homology demonstrated high levels of autoantibodies implicating the importance of shared conformational epitopes. To further explore the autoantigencity of Ro52, deletion and point mutant analyses were employed revealing previously hidden, robust autoantibodies directed against its C-terminal immunoglobulin-binding domain. Another autoantibody, rheumatoid factor, targeting the Fc region of IgG, strongly overlapped with Ro52 seropositivity (odds ratio 14; P < 0.0001). These convergent mechanistic findings support a model whereby intracellular Ro52-bound antibody-coated pathogen complexes, released or misprocessed from infected cells, drive autoantigenicity against Ro52 and the Fc region of IgG. More... »

PAGES

3345

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41598-018-21522-7

DOI

http://dx.doi.org/10.1038/s41598-018-21522-7

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1101045841

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/29463848


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Download the RDF metadata as:  json-ld nt turtle xml License info

HOW TO GET THIS DATA PROGRAMMATICALLY:

JSON-LD is a popular format for linked data which is fully compatible with JSON.

curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1038/s41598-018-21522-7'

N-Triples is a line-based linked data format ideal for batch operations.

curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/s41598-018-21522-7'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/s41598-018-21522-7'

RDF/XML is a standard XML format for linked data.

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/s41598-018-21522-7'


 

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