Ectopic Lymphoid Structures Support Ongoing Production of Class-Switched Autoantibodies in Rheumatoid Synovium
Frances Humby,Michele Bombardieri,Antonio Manzo,Stephen Kelly,Mark Blades,Bruce Kirkham,Jo Spencer,Costantino Pitzalis +7 more
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TLDR
It is demonstrated that FDC+ follicular units invariably express AID and are surrounded by ACPA-producing plasma cells, providing strong evidence that ectopic lymphoid structures in the RA synovium are functional and support autoantibody production.Abstract:
Background
Follicular structures resembling germinal centres (GCs) that are characterized by follicular dendritic cell (FDC) networks have long been recognized in chronically inflamed tissues in autoimmune diseases, including the synovium of rheumatoid arthritis (RA). However, it is debated whether these ectopic structures promote autoimmunity and chronic inflammation driving the production of pathogenic autoantibodies. Anti-citrullinated protein/peptide antibodies (ACPA) are highly specific markers of RA, predict a poor prognosis, and have been suggested to be pathogenic. Therefore, the main study objectives were to determine whether ectopic lymphoid structures in RA synovium: (i) express activation-induced cytidine deaminase (AID), the enzyme required for somatic hypermutation and class-switch recombination (CSR) of Ig genes; (ii) support ongoing CSR and ACPA production; and (iii) remain functional in a RA/severe combined immunodeficiency (SCID) chimera model devoid of new immune cell influx into the synovium.read more
Citations
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References
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Journal ArticleDOI
The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis.
Frank C. Arnett,Steven M. Edworthy,Daniel A. Bloch,Dennis J. McShane,James F. Fries,Norman S. Cooper,L. A. Healey,Stephen R. Kaplan,Matthew H. Liang,Harvinder S. Luthra,Thomas A. Medsger,Donald M. Mitchell,David H. Neustadt,Robert S. Pinals,Jane G. Schaller,John T. Sharp,Ronald L. Wilder,Gene G. Hunder +17 more
TL;DR: The revised criteria for the classification of rheumatoid arthritis (RA) were formulated from a computerized analysis of 262 contemporary, consecutively studied patients with RA and 262 control subjects with rheumatic diseases other than RA (non-RA).
Journal Article
Revised criteria for the classification of rheumatoid arthritis.
TL;DR: The Bulletin on the Rheumatic Diseases has published all of the classification criteria for the rheumatic diseases to date, and these new revised classified criteria for rheumatoid arthritis are very important as they should provide understanding of the possibly changing face of rheumatism.
Journal ArticleDOI
Revised criteria for the classification of rheumatoid arthritis.
TL;DR: The Bulletin on the Rheumatic Diseases has published all of the classification criteria for rheumatic diseases to date as mentioned in this paper, and these new revised classification criteria are very important as they should provide understanding of the possibly changing face of rheumatoid arthritis.
Journal ArticleDOI
Class Switch Recombination and Hypermutation Require Activation-Induced Cytidine Deaminase (AID), a Potential RNA Editing Enzyme
Masamichi Muramatsu,Kazuo Kinoshita,Sidonia Fagarasan,Shuichi Yamada,Yoichi Shinkai,Tasuku Honjo +5 more
TL;DR: Results suggest that AID may be involved in regulation or catalysis of the DNA modification step of both class switching and somatic hypermutation in CH12F3-2 B lymphoma.
Journal ArticleDOI
Citrulline is an essential constituent of antigenic determinants recognized by rheumatoid arthritis-specific autoantibodies.
G.A. Schellekens,B.A. de Jong,F.H.J. van den Hoogen,L. B. A. Van De Putte,W. J. Van Venrooij +4 more
TL;DR: It is shown that autoantibodies reactive with synthetic peptides containing the unusual amino acid citrulline, a posttranslationally modified arginine residue, are specifically present in the sera of RA patients, and the presence of these antibodies early in disease, even before other disease manifestations occur, are indicative for a possible role of citrulling epitopes in the pathogenesis of RA.