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MS analysis of rheumatoid arthritic synovial tissue identifies specific citrullination sites on fibrinogen.
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
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2010 (English)In: Proteomics - Clinical Applications, ISSN 1862-8354, Vol. 4, no 5, 511-518 p.Article in journal (Refereed) Published
Abstract [en]

Purpose

Citrullination is a post-translational modification of arginine residues to citrulline catalyzed by peptidyl arginine deiminases. Induced expression of citrullinated proteins are frequently detected in various inflammatory states including arthritis; however, direct detection of citrullination in arthritic samples has not been successfully performed in the past.

Experimental design

Citrullination of human fibrinogen, a candidate autoantigen in arthritis, was studied. Accurate identification of citrullinated fibrinogen peptides from rheumatoid arthritis synovial tissue specimens was performed using accurate mass and retention time analysis.

Results

A peptide with the sequence ESSSHHPGIAEFPSRGK corresponding to amino acids 559-575 of fibrinogen a-chain was identified to be citrullinated with an occupancy rate between 1.4 and 2.5%. Citrullination of the peptide KREEAPSLRPAPPPISGGGYRARPAK corresponding to amino acids 52-77 of the fibrinogen beta-chain was identified with an occupancy rate of 1.2%.

Conclusions and clinical relevance

We report a proof of principle study for the identification of citrullinated proteins and within them, identification of citrullination sites and quantification of their occupancies in synovial tissue from rheumatoid arthritis patients using high-resolution MS. Detailed studies on which molecules are citrullinated in arthritis can provide information about their role in immune regulation and serve as novel biomarkers and potentially even as therapeutic targets.

Place, publisher, year, edition, pages
2010. Vol. 4, no 5, 511-518 p.
Keyword [en]
Citrullination, fibrinogen, MS, rheumatoid arthritis
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-136069DOI: 10.1002/prca.200900088ISI: 000278432700004PubMedID: 21137068OAI: oai:DiVA.org:uu-136069DiVA: diva2:376140
Available from: 2010-12-10 Created: 2010-12-09 Last updated: 2011-04-05Bibliographically approved

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Artemenko, Konstantin

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