Guillaume Beltramo1, Gabriel Thabut2, Nicolas Peron1, Pascale Nicaise3, Aurélie Cazes4, Marie-Pierre Debray5, Audrey Joannes6, Yves Castier7, Arnaud A Mailleux6, Justine Frija8, Pauline Pradère1, Aurélien Justet9, Raphaël Borie9, Marie-Christine Dombret9, Camille Taille9, Michel Aubier9, Bruno Crestani10. 1. Assistance Publique-Hôpitaux de Paris, DHU FIRE (Fibrosis, Inflammation and Remodeling), Hôpital Bichat, Service de Pneumologie A, 75018 Paris, France. 2. Assistance Publique-Hôpitaux de Paris, Hôpital Bichat, Service de Pneumologie et Transplantation, 75018 Paris, France; INSERM UMR 1152, Labex Inflamex, Paris, France; Université Paris Diderot, Paris, France. 3. Assistance Publique-Hôpitaux de Paris, Hôpital Bichat, Département d'Hématologie et Immunologie UF Autoimmunité et Hypersensibilités, 75018 Paris, France. 4. INSERM UMR 1152, Labex Inflamex, Paris, France; Université Paris Diderot, Paris, France; Assistance Publique-Hôpitaux de Paris, Hôpital Bichat, Département d'Anatomie Pathologique, 75018 Paris, France. 5. Assistance Publique-Hôpitaux de Paris, Hôpital Bichat, Service de Radiologie, Paris, France. 6. INSERM UMR 1152, Labex Inflamex, Paris, France; Université Paris Diderot, Paris, France. 7. INSERM UMR 1152, Labex Inflamex, Paris, France; Université Paris Diderot, Paris, France; Assistance Publique-Hôpitaux de Paris, Hôpital Bichat, Service de Chirurgie Vasculaire et Thoracique 75018 Paris, France. 8. Université Paris Diderot, Paris, France; Assistance Publique-Hôpitaux de Paris, Hôpital Bichat, Service d'Explorations Fonctionnelles Multidisciplinaires, 75018 Paris, France. 9. Assistance Publique-Hôpitaux de Paris, DHU FIRE (Fibrosis, Inflammation and Remodeling), Hôpital Bichat, Service de Pneumologie A, 75018 Paris, France; INSERM UMR 1152, Labex Inflamex, Paris, France; Université Paris Diderot, Paris, France. 10. Assistance Publique-Hôpitaux de Paris, DHU FIRE (Fibrosis, Inflammation and Remodeling), Hôpital Bichat, Service de Pneumologie A, 75018 Paris, France; INSERM UMR 1152, Labex Inflamex, Paris, France; Université Paris Diderot, Paris, France. Electronic address: bruno.crestani@aphp.fr.
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 PaO2 (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.
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 PaO2 (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.