Proteome Analysis of Rheumatoid Arthritis Gut Mucosa

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

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

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.

OriginalsprogEngelsk
TidsskriftJournal of Proteome Research
Vol/bind16
Udgave nummer1
Sider (fra-til)346-354
ISSN1535-3893
DOI
StatusUdgivet - 2017

Fingeraftryk

Proteome
Mucous Membrane
Tetrahydrofolate Dehydrogenase
Biopsy
leflunomide
Proteins
Methotrexate
Peptides
Colon
Antibodies
Confocal microscopy
Cartilage
Immunosuppressive Agents
Labels
Joint Diseases
Membrane Proteins
Confocal Microscopy
Cytosol
Joints
Epithelial Cells

Citer dette

Bjerg Bennike, T., Ellingsen, T., Glerup, H., Bonderup, O. K., Carlsen, T. G., Meyer, M. K., ... Stensballe, A. (2017). Proteome Analysis of Rheumatoid Arthritis Gut Mucosa. Journal of Proteome Research, 16(1), 346-354. https://doi.org/10.1021/acs.jproteome.6b00598
Bjerg Bennike, Tue ; Ellingsen, Torkell ; Glerup, Henning ; Bonderup, Ole Kristian ; Carlsen, Thomas Gelsing ; Meyer, Michael Kruse ; Bøgsted, Martin ; Christiansen, Gunna ; Birkelund, Svend ; Andersen, Vibeke ; Stensballe, Allan. / Proteome Analysis of Rheumatoid Arthritis Gut Mucosa. I: Journal of Proteome Research. 2017 ; Bind 16, Nr. 1. s. 346-354.
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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.",
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Bjerg Bennike, T, Ellingsen, T, Glerup, H, Bonderup, OK, Carlsen, TG, Meyer, MK, Bøgsted, M, Christiansen, G, Birkelund, S, Andersen, V & Stensballe, A 2017, 'Proteome Analysis of Rheumatoid Arthritis Gut Mucosa', Journal of Proteome Research, bind 16, nr. 1, s. 346-354. https://doi.org/10.1021/acs.jproteome.6b00598

Proteome Analysis of Rheumatoid Arthritis Gut Mucosa. / Bjerg Bennike, Tue; Ellingsen, Torkell; Glerup, Henning; Bonderup, Ole Kristian; Carlsen, Thomas Gelsing; Meyer, Michael Kruse; Bøgsted, Martin; Christiansen, Gunna; Birkelund, Svend; Andersen, Vibeke; Stensballe, Allan.

I: Journal of Proteome Research, Bind 16, Nr. 1, 2017, s. 346-354.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Proteome Analysis of Rheumatoid Arthritis Gut Mucosa

AU - Bjerg Bennike, Tue

AU - Ellingsen, Torkell

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

PY - 2017

Y1 - 2017

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.

U2 - 10.1021/acs.jproteome.6b00598

DO - 10.1021/acs.jproteome.6b00598

M3 - Journal article

VL - 16

SP - 346

EP - 354

JO - Journal of Proteome Research

JF - Journal of Proteome Research

SN - 1535-3893

IS - 1

ER -

Bjerg Bennike T, Ellingsen T, Glerup H, Bonderup OK, Carlsen TG, Meyer MK et al. Proteome Analysis of Rheumatoid Arthritis Gut Mucosa. Journal of Proteome Research. 2017;16(1):346-354. https://doi.org/10.1021/acs.jproteome.6b00598