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BPI‐ANCA of pediatric cystic fibrosis patients can impair BPI‐mediated killing of E. coli DH5α in vitro
Author(s) -
Schultz Hendrik,
Schinke Susanne,
Mosler Katharina,
Herlyn Karen,
Schuster Antje,
Gross Wolfgang L.
Publication year - 2004
Publication title -
pediatric pulmonology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.866
H-Index - 106
eISSN - 1099-0496
pISSN - 8755-6863
DOI - 10.1002/ppul.10416
Subject(s) - cystic fibrosis , medicine , antibiotics , immunology , microbiology and biotechnology , biology
Gram‐negative bacterial lung infections and chronic bacterial colonization are major threats for pediatric cystic fibrosis (CF) patients. Besides impeded mucociliary clearance, other mechanisms that contribute to increased susceptibility to infections are presumed. The bactericidal/permeability‐increasing protein (BPI), which is delivered by neutrophil granulocytes and mucosal epithelial cells, is one of the most potent innate antibiotics against Gram‐negative bacteria and endotoxin. Antineutrophil cytoplasmic autoantibodies against BPI (BPI‐ANCA) have been found in up to 90% of CF patients, and titers correlated inversely with lung function parameters. As major pulmonary damage is mediated by Gram‐negative bacteria and their products, the question was raised as to whether BPI‐ANCA can inhibit the antibiotic function of BPI in these patients. Sera of 23 pediatric CF patients were analyzed for the presence of BPI‐ANCA by indirect immunofluorescence, ELISA, epitope mapping, and Western blotting. Patients' IgG were tested in a bacterial growth inhibition assay with recombinant BPI (rBPI) and an amino‐terminal fragment of BPI (rBPI 21 ) that retains antibiotic activity for inhibition of the antibiotic function of BPI against E. coli DH5α in vitro. BPI was recognized by 21 of 23 patients' sera in our detection assays. Thirteen of 23 patients' BPI‐ANCA (56%) could inhibit the antibiotic function in vitro. Moreover, epitope mapping over the whole BPI sequence revealed that more patients' BPI‐ANCA recognize the amino‐terminal part of BPI than can be detected by ELISA. Thus, in pediatric CF patients, BPI‐ANCA may contribute to diminished bacterial clearance by inhibiting the antibiotic function of BPI. Pediatr Pulmonol. 2004; 37:158–164. © 2004 Wiley‐Liss, Inc.