Anti-protein arginine deiminase antibodies are distinctly associated with joint and lung involvement in rheumatoid arthritis.

OBJECTIVES: Rheumatoid arthritis (RA) is a chronic inflammatory disease in which possible interstitial lung disease (ILD) is an extra-articular manifestation that carries significant morbidity and mortality. Rheumatoid Factors (RF) and anti-citrullinated protein antibodies (ACPA) are included in the RA classification criteria but prognostic and diagnostic biomarkers for disease endotyping and RA-ILD are lacking. Anti-protein arginine deiminase antibodies (anti-PAD) are a novel class of autoantibodies identified in RA. This study aimed to assess clinical features, ACPA, and anti-PAD antibodies in RA patients with articular involvement and ILD.

METHODS: We retrospectively collected joint erosions, space narrowing, clinical features, and lung involvement of a cohort of seventy-one patients fulfilling the 2010 ACR/EULAR RA classification criteria. Serum samples from these patients were tested for ACPA IgG (QUANTA Flash CCP3), and anti-PAD3 and anti-PAD4 IgG, measured with novel assays based on a particle-based multi-analyte technology (PMAT).

RESULTS: Anti-PAD4 antibodies were significantly associated with radiographic injury (p= 0.027) and erosions (p= 0.02). Similarly, ACPA levels were associated with erosive disease (p= 0.014). Anti-PAD3/4 double positive patients displayed more joint erosions than patients with anti-PAD4 antibodies only or negative for both (p= 0.014 and p= 0.037, respectively). RA-ILD (15.5%, 11/71 patients) was associated with older age (p< 0.001), shorter disease duration (p= 0.045) and less erosive disease (p= 0.0063). ACPA were elevated in RA-ILD, while anti-PAD4 were negatively associated (p= 0.043).

CONCLUSION: Anti-PAD4 and anti-PAD3 antibodies identify RA-patient with higher radiographic injury and bone erosions. In our cohort, ILD is associated with lower radiographic and erosive damage, as well as low levels of anti-PAD4 antibodies.