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Synovial detection and autoantibody reactivity of processed citrullinated isoforms of vimentin in inflammatory arthritides

Kelly Tilleman UGent, Katleen Van Steendam, Tineke Cantaert, Filip De Keyser UGent, Dirk Elewaut UGent and Dieter Deforce UGent (2008) RHEUMATOLOGY. 47(5). p.597-604
abstract
Objectives. To investigate the presence and characteristics of citrullinated vimentin in protein extracts of inflamed synovial tissue. Methods. Cytosolic protein extracts obtained from RA (n = 14) and SpA patients (n = 14) were analysed by gel electrophoresis and western blotting. Citrullinated vimentin isoforms were visualized by a combination of anti-modified citrulline (AMC) staining and anti-vimentin detections (V9, H-84). This was subsequently confirmed by immunoprecipitation. Autoantibody detection was verified using sera obtained form RA (n = 6) and SpA (n = 6) patients. Results. A specific cluster of spots displayed on the 2D gel images of cytosolic synovial tissue extracts, was identified by mass spectrometry as vimentin. Interestingly, our results suggested that these isoforms could be the result of caspase cleavage. In addition, these cleaved forms of vimentin were found to be citrullinated in synovial cytosolic protein extracts of inflammatory arthritides, mainly in RA patients. Caspase-3 is able to cleave vimentin at amino acid 85. Western blot analysis with a specific antibody against amino acids 1-84 of vimentin (H-84) confirmed that the citrullinated isoforms of vimentin were lacking this part of the protein. These results were also confirmed by immunoprecipitation of vimentin derived from cytosolic protein extracts of RA and SpA patients. Furthermore, the presence of autoantibodies against these citrullinated processed forms of vimentin was found to be predominantly associated with RA patients. Conclusions. These findings show the presence of processed citrullinated vimentin in inflammatory arthritides, mainly in RA and suggest a possible origin of the ACPA immune response in RA.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
autoantibodies, rheumatoid arthritis, inflammation, human, citrullinated vimentin, ANTI-SA ANTIBODIES, RHEUMATOID-ARTHRITIS, INTERMEDIATE-FILAMENTS, RECENT-ONSET, DIAGNOSTIC-VALUE, EXPRESSION, PEPTIDE, PROTEIN, CLASSIFICATION, DEIMINATION
journal title
RHEUMATOLOGY
Rheumatology
volume
47
issue
5
pages
597-604 pages
Web of Science type
Article
Web of Science id
000255315700008
JCR category
RHEUMATOLOGY
JCR impact factor
4.136 (2008)
JCR rank
7/22 (2008)
JCR quartile
2 (2008)
ISSN
1462-0324
DOI
10.1093/rheumatology/ken077
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
432621
handle
http://hdl.handle.net/1854/LU-432621
date created
2008-10-24 10:06:00
date last changed
2016-12-19 15:44:31
@article{432621,
  abstract     = {Objectives. To investigate the presence and characteristics of citrullinated vimentin in protein extracts of inflamed synovial tissue.
Methods. Cytosolic protein extracts obtained from RA (n = 14) and SpA patients (n = 14) were analysed by gel electrophoresis and western blotting. Citrullinated vimentin isoforms were visualized by a combination of anti-modified citrulline (AMC) staining and anti-vimentin detections (V9, H-84). This was subsequently confirmed by immunoprecipitation. Autoantibody detection was verified using sera obtained form RA (n = 6) and SpA (n = 6) patients.
Results. A specific cluster of spots displayed on the 2D gel images of cytosolic synovial tissue extracts, was identified by mass spectrometry as vimentin. Interestingly, our results suggested that these isoforms could be the result of caspase cleavage. In addition, these cleaved forms of vimentin were found to be citrullinated in synovial cytosolic protein extracts of inflammatory arthritides, mainly in RA patients. Caspase-3 is able to cleave vimentin at amino acid 85. Western blot analysis with a specific antibody against amino acids 1-84 of vimentin (H-84) confirmed that the citrullinated isoforms of vimentin were lacking this part of the protein. These results were also confirmed by immunoprecipitation of vimentin derived from cytosolic protein extracts of RA and SpA patients. Furthermore, the presence of autoantibodies against these citrullinated processed forms of vimentin was found to be predominantly associated with RA patients.
Conclusions. These findings show the presence of processed citrullinated vimentin in inflammatory arthritides, mainly in RA and suggest a possible origin of the ACPA immune response in RA.},
  author       = {Tilleman, Kelly and Van Steendam, Katleen and Cantaert, Tineke and De Keyser, Filip and Elewaut, Dirk and Deforce, Dieter},
  issn         = {1462-0324},
  journal      = {RHEUMATOLOGY},
  keyword      = {autoantibodies,rheumatoid arthritis,inflammation,human,citrullinated vimentin,ANTI-SA ANTIBODIES,RHEUMATOID-ARTHRITIS,INTERMEDIATE-FILAMENTS,RECENT-ONSET,DIAGNOSTIC-VALUE,EXPRESSION,PEPTIDE,PROTEIN,CLASSIFICATION,DEIMINATION},
  language     = {eng},
  number       = {5},
  pages        = {597--604},
  title        = {Synovial detection and autoantibody reactivity of processed citrullinated isoforms of vimentin in inflammatory arthritides},
  url          = {http://dx.doi.org/10.1093/rheumatology/ken077},
  volume       = {47},
  year         = {2008},
}

Chicago
Tilleman, Kelly, Katleen Van Steendam, Tineke Cantaert, Filip De Keyser, Dirk Elewaut, and Dieter Deforce. 2008. “Synovial Detection and Autoantibody Reactivity of Processed Citrullinated Isoforms of Vimentin in Inflammatory Arthritides.” Rheumatology 47 (5): 597–604.
APA
Tilleman, Kelly, Van Steendam, K., Cantaert, T., De Keyser, F., Elewaut, D., & Deforce, D. (2008). Synovial detection and autoantibody reactivity of processed citrullinated isoforms of vimentin in inflammatory arthritides. RHEUMATOLOGY, 47(5), 597–604.
Vancouver
1.
Tilleman K, Van Steendam K, Cantaert T, De Keyser F, Elewaut D, Deforce D. Synovial detection and autoantibody reactivity of processed citrullinated isoforms of vimentin in inflammatory arthritides. RHEUMATOLOGY. 2008;47(5):597–604.
MLA
Tilleman, Kelly, Katleen Van Steendam, Tineke Cantaert, et al. “Synovial Detection and Autoantibody Reactivity of Processed Citrullinated Isoforms of Vimentin in Inflammatory Arthritides.” RHEUMATOLOGY 47.5 (2008): 597–604. Print.