Background/Purpose

We have previously demonstrated that lung abnormalities are present already at disease onset in ACPA positive RA patients. We aimed to further investigate lung changes in patients with rheumatoid arthritis (RA) in dynamic in a follow-up clinical study.

Methods

105 RA patients (with patient-reported symptom duration less than 1 year and naive to DMARD treatment) were investigated by lung HRCT and functional pulmonary testing at disease onset and 6 months after. All patients were started on methotrexate. A smaller subgroup of these patients (n=24) were subjected to bronchoscopy and mucosal large bronchial biopsies and bronchoalveolar lavage (BAL) samples were retrieved at disease onset (n=24) and after 6 months (n=21). Additional 16 large bronchial biopsies and 79 BAL samples from healthy volunteers were available.  Histological analysis for identification of inducible bronchia associated lymphoid tissues (iBALT) and lymphocyte infiltration were performed. Further immunohistochemical analysis was performed in RA biopsies to detect PAD enzymes, CD3, HLA-DQ and HLA-DR and to identify citrullinated targets. 

Results

Both parenchymal and airway HRCT abnormalities were more frequent among RA patients than controls (54% as compared to 30%, OR 2.7, p<0.05 for parenchymal changes and 66% as compared 42%, OR 2.7, p<0.05 for airway changes). Fibrosis (12/105, 11%) was solely detected in RA patients. At follow up 4 out of these 12 patients show some progress signs while the remaining 8 were stable.

Bronchial lymphocyte infiltration and iBALT formation was observed at baseline in half of the ACPA+ RA patients but only 1 out of 6 ACPA- patients (17%) and 1 out of 9 healthy volunteers (10%). Signs of such infiltration were still present at 6 months. Higher expression of HLA-DR, HLA-DQ and citrullinated targets was observed in bronchial biopsies of ACPA+ as compare to ACPA- RA (p<0.05). CD3 expression also showed a tendency to higher expression in the ACPA+ as compared to ACPA- RA patients. HLA-DR expression showed a tendency to decrease at 6 months but no significant changes were observed.

ACPA+ RA patients had significantly higher proportions of BAL lymphocytes and neutrophils as compared to healthy controls (p<0.05). The increased relative numbers of BAL lymohcoytes at disease onset was found reduced after 6 months of treatment (p<0.05). Markers of T cell activation (CD69 and CD103) were expressed by significantly more CD4+ BAL T cells in ACPA+ RA patients as compared to healthy controls, but no significant changes were observed at follow-up.

Conclusion

HRCT changes, signs of inflammation and accumulation of highly activated and differentiated BAL CD4+ T cells are present early in the lungs of ACPA+ RA patients and show relatively minimal changes during 6 months follow-up.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/characterization-of-lung-inflammation-in-the-lungs-of-early-rheumatoid-arthritis/