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

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Immune Tolerance
Joint Diseases
Post Translational Protein Processing
Rheumatoid Arthritis
Colon
Mucous Membrane
Tetrahydrofolate Dehydrogenase
Proteins
leflunomide
Methotrexate
Biopsy
Peptides
Antibodies
Proteome
Colonoscopy
Immunosuppressive Agents
Confocal Microscopy
Cytosol
Proteomics
Cartilage

Bibliographical note

ISSN 2573-0355

Keywords

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

Cite this

@article{6468eedd17c54f769207833c4172e0a8,
title = "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",
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.",
keywords = "acpa, dhfr, rheumatoid arthritis, anti-citrullinted protein antibody, citrullination, colon, mucosa, dihydrofolate reductase, leflunomide, Methotrexate, proteomics",
author = "Bennike, {Tue Bjerg} and Ellingsen, {Torkell Juulsgaad} and Henning Glerup and Bonderup, {Ole Kristian} and Carlsen, {Thomas Gelsing} and Meyer, {Michael Kruse} and Martin B{\o}gsted and Gunna Christiansen and Svend Birkelund and Vibeke Andersen and Allan Stensballe",
note = "ISSN 2573-0355",
year = "2017",
month = "6",
language = "English",
journal = "Biomedical Advances",
issn = "2573-0355",

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TY - JOUR

T1 - The colon mucosa is a potential site for the initial triggering of Rheumatoid Arthritis

T2 - 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

AU - Bennike, Tue Bjerg

AU - Ellingsen, Torkell Juulsgaad

AU - Glerup, Henning

AU - Bonderup, Ole Kristian

AU - Carlsen, Thomas Gelsing

AU - Meyer, Michael Kruse

AU - Bøgsted, Martin

AU - Christiansen, Gunna

AU - Birkelund, Svend

AU - Andersen, Vibeke

AU - Stensballe, Allan

N1 - ISSN 2573-0355

PY - 2017/6

Y1 - 2017/6

N2 - 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.

AB - 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.

KW - acpa

KW - dhfr

KW - rheumatoid arthritis

KW - anti-citrullinted protein antibody

KW - citrullination

KW - colon

KW - mucosa

KW - dihydrofolate reductase

KW - leflunomide

KW - Methotrexate

KW - proteomics

UR - http://pubs.acs.org/doi/abs/10.1021/acs.jproteome.6b00598?src=recsys

M3 - Journal article

JO - Biomedical Advances

JF - Biomedical Advances

SN - 2573-0355

ER -