The role for neutrophil extracellular traps in cystic fibrosis autoimmunity

• DOI: 10.1172/jci.insight.88912
• Publication Date: 2016-10-19T15:00:59Z
• Authors: Sladjana Skopelja; B. JoNell Hamilton; Jonathan D. Jones; Mei-Ling Yang; Mark Mamula; Alix Ashare; Alex H. Gifford; William F.C. Rigby
• Keywords: Neutrophil Extracellular Traps; Extracellular Vesicles

While respiratory failure in cystic fibrosis (CF) frequently associates with chronic infection by Pseudomonas aeruginosa, no single factor predicts the extent of lung damage CF. To elucidate other causes, we studied autoantibody profile CF and rheumatoid arthritis (RA) patients, given similar association airway inflammation autoimmunity RA. Even though observed that bactericidal permeability-increasing protein (BPI), carbamylated proteins, citrullinated proteins all localized to neutrophil extracellular traps (NETs), which are implicated development autoimmunity, our study demonstrates striking specificity Particularly, patients developed anti-BPI autoantibodies but hardly any anti-citrullinated (ACPA). In contrast, ACPA-positive RA exhibited reactivity BPI. Interestingly, anti-carbamylated (ACarPA) were found both cohorts did not cross-react Contrary ACPA ACarPA, recognized BPI C-terminus absence posttranslational modifications. fact, discovered P. aeruginosa–mediated NET formation results cleavage aeruginosa elastase, suggests a novel mechanism accordance this model, associated presence on sputum culture. Finally, provide role for disease severity, as levels associate diminished function.