Presentation and progression of MPO-ANCA interstitial lung disease.

The association between MPO-ANCA-associated vasculitis (AAV) and interstitial lung disease (ILD) has been well established. Pulmonary fibrosis may coexist with, follow, or even precede the diagnosis of AAV, and its presence adversely affects the prognosis. The optimal approach to investigating ANCA in patients with ILD remains a subject of ongoing debate. Here we aim to describe presentation and progression of MPO-ANCA ILD. We conducted a retrospective evaluation of a cohort of individuals diagnosed with MPO-ANCA ILD, with or without accompanying renal impairment, at the Immunology and Cell Therapy Unit, Careggi University Hospital, Florence, Italy, between June 2016 and June 2022. Clinical records, imaging studies, pathologic examinations, and laboratory test results were collected. Among the 14 patients identified with MPO-ANCA ILD, we observed a significant association between MPO-ANCA titers assessed at the time of ILD diagnosis and renal involvement. Renal impairment in these cases often manifested as subclinical or slowly progressive kidney damage. Interestingly, complement C3 deposits were consistently found in all renal biopsy specimens, thereby suggesting the potential for novel therapeutic targets in managing renal complications associated with MPO-ANCA ILD. The presentation of MPO-ANCA vasculitis as ILD can be the first and only clinical manifestation. MPO-ANCA levels at ILD diagnosis could warn on the progression to renal involvement in patients with MPO-ANCA ILD, hence caution is needed because renal disease can be subclinical or smoldering.

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

OBJECTIVES: RA is a chronic inflammatory disease in which possible interstitial lung disease (ILD) is an extra-articular manifestation that carries significant morbidity and mortality. RF and 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 71 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 patients 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.