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
SN - 2573-0355
JO - Biomedical Advances
JF - Biomedical Advances
ER -