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Anti-LPS IgA and IgG Can Inhibit Serum Killing of Pseudomonas aeruginosa in Patients with Cystic Fibrosis

Anti-LPS IgA and IgG Can Inhibit Serum Killing of Pseudomonas aeruginosa in Patients with Cystic Fibrosis

Authors :
David W. Reid
Carrie F. Coggon
Emma L. Ledger
Ian R. Henderson
Amy Pham
Daniel J. Smith
Timothy J. Wells
Scott C. Bell
Source :
Infect Immun
Publication Year :
2021
Publisher :
American Society for Microbiology, 2021.

Abstract

Pseudomonas aeruginosa is one of the principal pathogens implicated in respiratory infections of patients with cystic fibrosis (CF) and non-CF bronchiectasis. Previously, we demonstrated that impaired serum-mediated killing of P. aeruginosa was associated with increased severity of respiratory infections in patients with non-CF bronchiectasis. This inhibition was mediated by high titres of O-antigen-specific IgG2 antibodies that cloak the surface of the bacteria, blocking access to the membrane. Infection related symptomatology was ameliorated in patients by using plasmapheresis to remove the offending antibodies. To determine if these inhibitory 'cloaking antibodies' were prevalent in patients with CF, we investigated 70 serum samples from patients with P. aeruginosa infection, and five without P. aeruginosa infection. Thirty-two percent of patients had serum that inhibited the ability of healthy control serum to kill P. aeruginosa. Here we demonstrate that this inhibition of killing requires O-antigen expression. Furthermore, we reveal that while IgG alone can inhibit the activity of healthy control serum, O-antigen specific IgA in patient sera can also inhibited serum-killing. We found that antibody affinity, not just titre, was also important in the inhibition of serum-mediated killing. These studies provide novel insight into cloaking antibodies in human infection and may provide further options in CF and other diseases for treatment of recalcitrant P. aeruginosa infections.

Details

ISSN :
10985522 and 00199567
Volume :
89
Database :
OpenAIRE
Journal :
Infection and Immunity
Accession number :
edsair.doi.dedup.....26e9666e9a70e85f7c9428753c1aaa7f
Full Text :
https://doi.org/10.1128/iai.00412-21