The colon mucosa is a potential site for the initial triggering of Rheumatoid Arthritis: A study of proteins reveals that the colon mucosa is a potential site of immune tolerance break towards proteins with the post-translational modification citrullination, which could contribute to the onset of the joint disease rheumatoid arthritis

Tue Bjerg Bennike, Torkell Juulsgaad Ellingsen, Henning Glerup, Ole Kristian Bonderup, Thomas Gelsing Carlsen, Michael Kruse Meyer, Martin Bøgsted, Gunna Christiansen, Svend Birkelund, Vibeke Andersen, Allan Stensballe

Research output: Contribution to journalJournal articleCommunication

Abstract

Rheumatoid arthritis (RA) is an inflammatory joint disease leading to cartilage damage and ultimately impaired joint function. To gain new insight into the systemic immune manifestations of RA, we characterized the colon mucosa proteome from 11 RA-patients and 10 healthy controls. The biopsies were extracted by colonoscopy and analyzed by label-free quantitative proteomics, enabling the quantitation of 5366 proteins. The abundance of dihydrofolate reductase (DHFR) was statistically significantly increased in RA-patient biopsies compared with controls and correlated with the administered dosage of methotrexate (MTX), the most frequently prescribed immunosuppressive drug for RA. Additionally, our data suggest that treatment with Leflunomide, a common alternative to MTX, increases DHFR. The findings were supported by immunohistochemistry with confocal microscopy, which furthermore demonstrated that DHFR was located in the cytosol of the intestinal epithelial and interstitial cells. Finally, we identified 223 citrullinated peptides from 121 proteins. Three of the peptides were unique to RA. The list of citrullinated proteins was enriched in extracellular and membrane proteins and included known targets of anticitrullinated protein antibodies (ACPAs). Our findings support that the colon mucosa could trigger the production of ACPAs, which could contribute to the onset of RA. The MS data have been deposited to ProteomeXchange with identifiers PXD001608 and PXD003082.
Original languageEnglish
JournalBiomedical Advances
ISSN2573-0355
Publication statusPublished - Jun 2017

Bibliographical note

ISSN 2573-0355

Keywords

  • acpa
  • dhfr
  • rheumatoid arthritis
  • anti-citrullinted protein antibody
  • citrullination
  • colon
  • mucosa
  • dihydrofolate reductase
  • leflunomide
  • Methotrexate
  • proteomics

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