Proteome Analysis of Rheumatoid Arthritis Gut Mucosa

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.