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

Respir Med. 2018 Feb:135:15-21. doi: 10.1016/j.rmed.2017.12.011. Epub 2018 Jan 2.

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.

Keywords: Autoimmunity; Hydrogen / potassium ATPase; Idiopathic pulmonary fibrosis; Proton pump.

Publication types

  • Comparative Study

MeSH terms

  • Aged
  • Aged, 80 and over
  • Autoantibodies / immunology
  • Autoimmunity / immunology*
  • Blood Gas Analysis / trends
  • Disease Progression
  • Female
  • Follow-Up Studies
  • H(+)-K(+)-Exchanging ATPase / metabolism
  • Humans
  • Idiopathic Pulmonary Fibrosis / diagnostic imaging
  • Idiopathic Pulmonary Fibrosis / epidemiology
  • Idiopathic Pulmonary Fibrosis / immunology*
  • Idiopathic Pulmonary Fibrosis / physiopathology
  • Lung / diagnostic imaging
  • Lung / immunology*
  • Lung / physiopathology
  • Male
  • Middle Aged
  • Parietal Cells, Gastric / immunology*
  • Parietal Cells, Gastric / metabolism
  • Proton Pumps / metabolism
  • Respiratory Function Tests / methods
  • Retrospective Studies
  • Tomography, X-Ray Computed / methods
  • Vital Capacity / physiology

Substances

  • Autoantibodies
  • Proton Pumps
  • H(+)-K(+)-Exchanging ATPase