Background Interstitial lung disease (ILD) is detected until 60% of patients with rheumatoid arthritis (RA), but is clinically significant in around 10% of cases. It is one of the leading causes of disease and death in RA patients. High levels of anti-cyclic citrullinated peptide (CCP) autoantibodies are associated with co-occurrence of pulmonary disease and RA [1]. Moreover, the pulmonary fibrosis marker mucine (MUC-1) was described to be a predictive indicator for ILD [2]. The adjuvant-induced arthritis (AIA) model is commonly used to investigate arthritic diseases due to some pathophysiological similarities to human arthritis [3].

Objectives The first objective of this study was to investigate the pulmonary involvement occurring in the rat AIA model. The second objective was to investigate the presence of potential biomarkers such as CCP and MUC-1.

Methods This study was performed from lungs from 64 AIA rats and 6 control rats without arthritis. Lungs were collected to perform histological and immunological analyses. Pulmonary disease was measured with a score based on the percentage of lung damage and the thickness of the alveolar walls (0: absent, 1: mild, 2: moderate, or 3: severe). CCP and MUC-1 immunostaining was also performed.

Results A nonspecific interstitial lung disease was detected in the lungs of 80% of AIA rats, whereas only half control rats developed it. A heterogeneous percentage of lung damage was observed, which correlated with the thickness of the alveolar walls but not with arthritis severity. Granulomas were observed in the most affected lung tissues, with a slight fibrosis at their periphery. The number of CCP markings correlated positively with the percentage of lung damage in AIA rats. MUC-1 was found homogeneously in the lung tissue of control and AIA rats, but more prominently in the periphery of granulomas in AIA rats.

Conclusion We have described the pulmonary involvement in the AIA rat model, which developed the extra-articular complication similar to RA-ILD. We identified CCP and MUC-1 as potential biomarkers of this pulmonary involvement. Thus, the lung may be a site of initiation of CCP immunity. The AIA model will then allow a better understanding of RA-ILD, which may lead to earlier diagnosis and the potential development of new targeted therapies.

References [1]Aubart F, Crestani B, Nicaise-Roland P, Tubach F, Bollet C, Dawidowicz K, et al. High levels of anti-cyclic citrullinated peptide autoantibodies are associated with co-occurrence of pulmonary diseases with rheumatoid arthritis. J Rheumatol 2011;38:979–982.

[2]Elhai M, Avouac J, Allanore Y. Circulating lung biomarkers in idiopathic lung fibrosis and interstitial lung diseases associated with connective tissue diseases: Where do we stand? Semin Arthritis Rheum 2020;50:480–491.

[3]Courbon G, Cleret D, Linossier M-T, Vico L, Marotte H. Early Subchondral Bone Loss at Arthritis Onset Predicted Late Arthritis Severity in a Rat Arthritis Model: EARLY BONE LOSS AT ARTHRITIS. J Cell Physiol 2017;232:1318–1325. Available at: http://doi.wiley.com/10.1002/jcp.25601. Accessed October 20, 2020.

Acknowledgements: NIL.

Disclosure of Interests None Declared.