Anti-parietal cell autoimmunity is associated with an accelerated decline of lung function in IPF patients

Abstract Background Autoantibodies against lung epithelial antigens are often detected in patients with Idiopathic Pulmonary Fibrosis (IPF). Anti-Parietal Cell Antibodies (APCA) target the H+/K+ATPase (proton pump). APCA prevalence and lung H+/K+ATPase expression was never studied in IPF patients. Methods We retrospectively collected clinical, lung function and imaging data from APCA positive patients (APCA+IPF) and compared them with APCA negative IPF patients matched on the date of diagnostic assessment. H+/K+ATPase expression was assessed with immunohistochemistry and PCR. Results Among 138 IPF patients diagnosed between 2007 and 2014 and tested for APCA, 19 (13.7%) APCA+ patients were identified. APCA+IPF patients were 16 men and 3 women, mean age 71 years. The median titer of APCA was 1:160. A pernicious anemia was present in 5 patients and preceded the fibrosis in 3 cases. With a mean follow up of 31 months, 2 patients had an exacerbation and 7 patients died. As compared with 19 APCA- IPF patients, APCA+IPF patients had a less severe disease with better DLCO (57% vs 43% predicted), preserved PaO 2 (85 ± 8 mmHg vs 74 ± 11 mmHg), a lower rate of honeycombing on HRCT (58% vs 89%), but they experienced an accelerated decline of FVC (difference 61.4 ml/year; p = .0002). The H+/K+ATPase was strongly expressed by hyperplastic alveolar epithelial cells in the fibrotic lung. Conclusion Anti-parietal cell autoimmunity is detected in some IPF patients and is associated with an accelerated decline of lung function. Anti-parietal cell autoimmunity may promote lung fibrosis progression.