Background/Purpose: To investigate if lung changes are present in rheumatoid arthritis (RA) patients early in the disease process and to address the contribution of these changes to disease initiation.

Methods: 24 RA patients with patient-reported symptom duration less than 1 year and naive to DMARD treatment and 9 healthy individuals were subjected to bronchoscopy and mucosal large bronchial biopsies were retrieved. Histological analysis for identification of inducible bronchia associated lymphoid tissues (iBALT) and lymphocyte infiltration, as well as immunohistochemistry for PAD enzymes, CD3, HLA-DQ and HLA-DR were performed. Presence of citrullinated targets were detected by immunohistochemistry using biotinylated ACPA isolated from synovial fluid of RA patients. Mass spectrometry was used for identification of citrullinated epitopes in 6 of the lung biopsies and additional 8 synovial RA biopsies. An in house ELISA was set-up to measure reactivity against new identified citrullinated targets in the blood of RA patients in two distinct cohorts (in total 250 individuals).

Results:

Bronchial lymphocyte infiltration and iBALT formation was observed in half of the ACPA+ RA patients but only 1 out of 6 ACPA- patients (17%) and 1 out of 9 healthy volunteers (10%). Higher expression of CD3, HLA-DQ, HLA-DR and citrullinated targets was observed in bronchial biopsies of ACPA+ as compare to ACPA- RA. BAL fluids were enriched in both IgG and IgA ACPA as compared to paired serum samples. Mass spectometry identified 5 proteins in the synovium (in total 8 sites) and 4 in the lungs (in total 6 sites) containing citrullinated residues. Two vimentin derived citrullinated peptides were present in a majority of both synovial and lung biopsies with slightly higher citrullinated/unmodified peptides ratios in the smokers as compared to non-smokers. An average of 15% of the RA patients tested by ELISA showed antibody reactivity against one of the new identified citrullinated target. 

Conclusion: Signs of inflammation and local ACPA enrichment are present early in bronchial tissues of ACPA+ RA patients. Shared citrullinated targets in the lung and joints as well as systemic reactivity against these targets are present in RA patients. Our findings support the notion that early inflammatory events in the lungs may represent a critical initiating factor in the development of ACPA+ RA.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/characterization-of-lung-inflammation-and-identification-of-shared-citrullinated-targets-in-the-lungs-and-joints-of-early-ra/