Autoantibodies against bactericidal/permeability–increasing protein (BPI–ANCA) in cystic fibrosis patients treated with azithromycin

Abstract

Autoantibodies against bactericidal/permeability-increasing protein (BPI-ANCA) were found in patients with cystic fibrosis (CF). It is speculated that they represent a marker of the chronic endobronchial infection and sustained inflammatory response in CF. Our aim was to evaluate whether azithromycin (AZM), through its antiinflammatory effect, could affect the level of BPI-ANCA in CF patients. Eighteen patients with CF aged 5.5-36.3 years (median 15.1) were enrolled in a randomised, double-blind, placebo-controlled trial of AZM (250 mg twice a week to 10 patients) or placebo (8 patients) for 12 weeks. BPI-ANCA levels were recorded pre- and post-treatment and compared to a group of 18 matched healthy controls. Chi-square analysis, Kruskal-Wallis and Mann-Whitney tests were used to compare between the groups. Pre- and post-treatment values were compared using the Wilcoxon Signed-Ranked test. BPI-ANCA was found in 12 CF patients (67%) and four (22%) healthy subjects (P<0.001). The mean BPI-ANCA level was 3.94+/-6.15 U/ml (mean+/-SD) in healthy subjects and 38.11+/-42.34 U/ml in CF patients (P=0.023). The mean BPI-ANCA level was higher in patients with Pseudomonas aeruginosa compared to those without (64+/-35 U/ml and 25+/-41 U/ml respectively, P=0.032). No change in BPI-ANCA levels occurred in the AZM-treated patients [35 (0-127) U/ml (median (range) and 30 (0-120) U/ml, respectively] or in the placebo group [10 (0-66) U/ml and 13 (0-83) U/ml, respectively]. BPI-ANCA levels are significantly higher in patients with CF compared to healthy controls. BPIANCA levels are higher among patients colonised with P. aeruginosa. Twelve weeks of AZM therapy did not lower the BPI-ANCA level in patients with CF.

Glomerular Disease in Patients with Infectious Processes Developing Antineutrophil Cytoplasmic Antibodies

“…Other antigens that are sources of autoantibodies recognized by immunofluorescence ANCA assay include azurocidin, which appears to be related to ANCA secondary to drugs [185], lactoferrin [185], and so forth. Anti-BPI ANCA is detected with a high frequency in patients with cystic fibrosis and infections with Pseudomonas species [53–56] and those with inflammatory bowel disease or primary sclerosing cholangiitis and presumed infections from enteric Gram-negative bacteria [186]. Anti-BPI ANCA increases the severity of both pulmonary and gastrointestinal infections through reductions of the clearance of bacteria and endotoxin by the leucocytes and, probably, through other nonspecific effects on immune complexes [187].…”

Bactericidal/permeability increasing protein: A multifaceted protein with functions beyond LPS neutralization

“…Zhao et al have shown BPI to be one of the major ANCA antigens in CF patients. 72 The presence of both IgA and IgG anti-BPI auto-Abs have been correlated to the severity of lung disease associated with CF. 71 Both the isotypes against BPI were directed toward its carboxy terminal domain, which is important for opsonization.…”

Assessment of panobacumab as adjunctive immunotherapy for the treatment of nosocomial Pseudomonas aeruginosa pneumonia

“…The membrane-bound virulence factor lipopolysaccharide (LPS), expressed by all Gram-negative bacteria like P. aeruginosa, elicits an immunoglobulin M (IgM)-mediated antibody response that takes several days to fully develop, and this delay may increase the risk of death in severe infections [18]. Human monoclonal antibodies directed against P. aeruginosa LPS have demonstrated protection in various settings [19][20][21].…”