Format

Send to

Choose Destination

See 1 citation found by title matching your search:

J Cyst Fibros. 2019 Jan 10. pii: S1569-1993(18)30971-8. doi: 10.1016/j.jcf.2018.12.010. [Epub ahead of print]

Systemic levels of anti-PAD4 autoantibodies correlate with airway obstruction in cystic fibrosis.

Author information

1
Department of Infectious Diseases, College of Veterinary Medicine, The University of Georgia, Athens, GA, USA.
2
Division of Rheumatology, University of Michigan, School of Medicine, Ann Arbor, MI, USA.
3
Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, School of Medicine, Birmingham, AL, USA.
4
Department of Epidemiology & Biostatistics, College of Public Health, The University of Georgia, Athens, GA, USA.
5
Division of Pulmonology, Allergy/Immunology, Cystic Fibrosis and Sleep, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA.
6
Department of Infectious Diseases, College of Veterinary Medicine, The University of Georgia, Athens, GA, USA. Electronic address: radab@uga.edu.

Abstract

Cystic fibrosis (CF) airway disease is characterized by the long-term presence of neutrophil granulocytes. Formation of neutrophil extracellular traps (NETs) and/or autoantibodies directed against extracellular components of NETs are possible contributors to neutrophil-mediated lung damage in CF. The goal of this study was to measure their levels in CF adults compared to healthy controls and subjects with rheumatologic diseases known to develop NET-related autoantibodies and pathologies, rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Sera were analyzed from the following number of subjects: 37 CF, 23 healthy controls (HC), 20 RA, and 21 SLE. CF had elevated serum myeloperoxidase (MPO) concentrations (347.5±56.1 ng/ml, mean+/-S.E.M., p = .0132) compared to HC (144.5±14.6 ng/ml) but not of neutrophil elastase (NE) complexed with alpha-1-antitrypsin, cell-free DNA or NE-DNA complexes. The peptidylarginine deiminase 4 (PAD4) enzyme is required for NET formation and associated DNA release in neutrophils. Serum levels of anti-PAD4 antibodies (Ab) were elevated in CF (p = .0147) compared to HC and showed an inverse correlation with a measure of lung function, FEV1% predicted (r = -0.5020, p = .015), as did MPO levels (r = -0.4801, p = .0026). Anti-PAD4 Ab levels in CF sera associated with lung infection by P. aeruginosa, but not that by S. aureus, age, sex, CF-related diabetes or the presence of musculoskeletal pain. Serum levels of anti-citrullinated protein Abs (ACPAs) and anti-nucleosome Abs were not elevated in CF compared to HC (p = .7498, p = .0678). In summary, adult CF subjects develop an autoimmune response against NET components that correlates with worsening lung disease.

KEYWORDS:

Autoantibody; Cystic fibrosis; Lung disease, autoimmunity; Neutrophil extracellular traps; Neutrophils; PAD4

PMID:
30638826
DOI:
10.1016/j.jcf.2018.12.010

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center