Perinuclear-Antineutrophil Cytoplasmic Antibodies in Pulmonary Fibrosis

Abstract

PURPOSE: Idiopathic pulmonary fibrosis, characterized by usual interstitial pneumonia (UIP) is a progressive disorder with no proven therapy. Recurrent episodes of acute lung injury likely occur, with cumulative scarring and progression to end-stage fibrosis . Small case series have suggested that a subset of patients with UIP, have circulating perinuclear-antineutrophil cytoplasmic antibodies (P-ANCA) specific for myeloperoxidase (MPO) in peripheral blood. MPO/P-ANCA is frequently associated with vasculitis. The purpose of this study was to characterize the subset of patients diagnosed with pulmonary fibrosis (including UIP) who were P-ANCA positive. METHODS: A computerized search identified patients evaluated at our institution with ICD9 diagnosis code 516.3 (idiopathic fibrosing alveolitis) between 2000 and 2010 that also underwent P-ANCA testing. Patients were determined to have UIP based on surgical lung biopsy or characteristic CT scan findings. RESULTS: Of 658 patients with pulmonary fibrosis, 84 (13%) were P-ANCA positive. Of these 21 had confirmed, and 5 probable microscopic polyangiitis or Wegener's granulomatosis. 32 had connective tissue disease, most frequently nondifferentiated connective tissue disease, rheumatoid arthritis or scleroderma. Twenty P-ANCA positive patients had no clinical evidence of vasculitis or other systemic inflammatory disease. 41% of the P-ANCA positive patients were MPO positive. 23/26 with vasculitis were MPO positive compared to 11/58 of those without vasculitis, p<0.001. UIP tended to be more frequently seen in patients with vasculitis (18/26, 69%) than with connective tissue disease (15/32, 47%; p=0.08). MPO positivity was associated with a higher frequency of UIP (24/34, 71% versus 25/48, 52%; p=0.09). CONCLUSIONS: P-ANCA is present in a significant minority of patients with pulmonary fibrosis and tends to be associated with concomitant vasculitis or connective tissue disease. The presence of anti-MPO antibodies was associated with a higher frequency of vasculitis and/or a UIP pattern. CLINICAL IMPLICATIONS: In patients with pulmonary fibrosis the presence of PANCA as a marker of vasculitis and or connective tissue disease has potential therapeutic implications. Further studies are required to determine the clinical and prognostic significance of P-ANCA in pulmonary fibrosis.