Low-Avidity Autoantibodies against Bactericidal/Permeability-Increasing Protein Occur in Gram-Negative and Gram-Positive Bacteremia.

Publisher: American Society For Microbiology Country of Publication: United States NLM ID: 0246127 Publication Model: Electronic-Print Cited Medium: Internet ISSN: 1098-5522 (Electronic) Linking ISSN: 00199567 NLM ISO Abbreviation: Infect Immun Subsets: MEDLINE

Publication: Washington, DC : American Society For Microbiology
Original Publication: [Bethesda, Md.] American Society for Microbiology.

Antimicrobial Cationic Peptides/*immunology ; Autoantibodies/*immunology ; Bacteremia/*immunology ; Blood Proteins/*immunology ; Gram-Negative Bacterial Infections/*immunology ; Gram-Positive Bacterial Infections/*immunology ; Immunoglobulin G/*immunology; Acute Disease ; Antibody Affinity ; Antigens, Bacterial/immunology ; Autoantibodies/blood ; Bacteremia/microbiology ; Chronic Disease ; Escherichia coli/immunology ; Escherichia coli/isolation & purification ; Gram-Negative Bacterial Infections/microbiology ; Gram-Positive Bacterial Infections/microbiology ; Humans ; Immunoglobulin G/blood ; Kinetics ; Prospective Studies ; Pseudomonas aeruginosa/immunology ; Pseudomonas aeruginosa/isolation & purification ; Staphylococcus aureus/immunology ; Staphylococcus aureus/isolation & purification

Antibody autoreactivity against bactericidal/permeability-increasing protein (BPI) is strongly associated with Pseudomonas aeruginosa infection in cystic fibrosis (CF), non-CF bronchiectasis (BE), and chronic obstructive pulmonary disease (COPD). We examined the pathogen-specific nature of this autoreactivity by examining antibodies to BPI in bacteremia patients. Antibodies to BPI and bacterial antigens were measured in sera by ELISA from five patient cohorts ( n  = 214). Antibody avidity was investigated. Bacteremic patient sera ( n  = 32) exhibited IgG antibody autoreactivity against BPI in 64.7% and 46.7% of patients with positive blood cultures for P. aeruginosa and Escherichia coli , respectively. Autoantibody titers correlated with IgG responses to bacterial extracts and lipopolysaccharide (LPS). A prospective cohort of bacteremic patient sera exhibited anti-BPI IgG responses in 23/154 (14.9%) patients with autoreactivity present at the time of positive blood cultures in patients with Gram-negative and Gram-positive bacteria, including 8/60 (13.3%) patients with Staphylococcus aureus Chronic tissue infection with S. aureus was associated with BPI antibody autoreactivity in 2/15 patients (13.3%). Previously, we demonstrated that BPI autoreactivity in CF patient sera exhibits high avidity. Here, a similar pattern was seen in BE patient sera. In contrast, sera from patients with bacteremia exhibited low avidity. These data indicate that low-avidity IgG responses to BPI can arise acutely in response to bacteremia and that this association is not limited to P. aeruginosa This is to be contrasted with chronic respiratory infection with P. aeruginosa , suggesting that either the chronicity or the site of infection selects for the generation of high-avidity responses, with biologic consequences for airway immunity.
(Copyright © 2020 Theprungsirikul et al.)

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Keywords: BPI; Pseudomonas; Pseudomonas aeruginosa; autoimmunity; autoreactivity; bacteremia; bactericidal/permeability-increasing protein; bronchiectasis

0 (Antigens, Bacterial)
0 (Antimicrobial Cationic Peptides)
0 (Autoantibodies)
0 (Blood Proteins)
0 (Immunoglobulin G)
0 (bactericidal permeability increasing protein)

Date Created: 20200805 Date Completed: 20210402 Latest Revision: 20210402

20221213

PMC7504969

10.1128/IAI.00444-20

32747603