Background/Purpose:  The aims of the current study was to investigate if inflammatory lung changes are present in RA patients early in the disease process and to address the contribution of these changes to disease initiation.

Methods: 105 RA patients with symptom duration less than 1 year at the time of diagnosis and naive to DMARD treatment and 43 non-RA individuals, matched for age, smoking and gender were subject to high-resolution computer tomography (HRCT) of the lungs. In a subgroup of patients (n=21) bronchoscopy was performed and BAL samples as well as mucosal large bronchial biopsies were retrieved. Histological analysis for identification of inducible bronchia associated lymphoid tissues (iBALT), PAD enzymes, CD3, and HLA-DR expression were performed. Presence of ACPA was tested by ELISA in the serum and BAL. Mass spectrometry was used for identification of citrullinated epitopes in 6 of the lung biopsies and additional 8 synovial RA biopsies. Contingency tables and chi-square test as well as a generalized linear model were used for analysis of the clinical data. Man-Whitney test was used to analyze differences in immunohistochemistry double blind semi-quantitative scores between independent groups. 

Results: A large majority of ACPA+ RA patients (59%, 41/70) presented with HRCT lung abnormalities, as compared to only 34% (12/35) of ACPA- patients and 28% (12/43) of the controls (p<0.05). ACPA positive smokers had increased levels of expression of PAD enzymes in BAL. iBALT formation and higher expression of HLA-DR was observed in bronchial biopsies of ACPA positive RA. A majority of serum ACPA positive RA patients subjected to lung bronchoscopy had detectable levels of ACPA in the BAL fluids both IgA and IgG. IgG from BAL fluids of ACPA-positive patients showed a higher ACPA reactivity as compared to serum IgG from the same patients. 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.

Conclusion: Lung HRCT abnormalities and subclinical inflammation are present already at the earliest visit to a rheumatology specialist early after disease onset in ACPA+ RA patients. These findings suggest that the lungs might be the primary local initiation sites of the anti-citrulline response in RA.

---

« Back to 2012 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/early-signs-of-subclinical-inflammation-and-local-antibody-production-in-early-rheumatoid-lungs/