Anti‐neutrophil cytoplasmic antibodies (ANCA) against bactericidal/permeability‐increasing protein (BPI) and cystic fibrosis lung disease

• Published in: Clinical and experimental immunology Vol. 117; no. 3; pp. 561 - 567
• Main Authors: MAHADEVA, R, DUNN, A. C, LOCKWOOD, C. M, WESTERBEEK, R. C, SHARPLES, L, WHITEHOUSE, D. B, CARROLL, N. R, ROSS-RUSSELL, R. I, WEBB, A. K, BILTON, D, LOMAS, D. A
• Format: Journal Article
• Language: English
• Published: Oxford BSL Blackwell Science Ltd 01.09.1999; Blackwell; Oxford University Press; Blackwell Science Inc
• Subjects: Adolescent; Adult; alpha 1-Antitrypsin - immunology; Antibodies, Antineutrophil Cytoplasmic - blood; Antibodies, Antineutrophil Cytoplasmic - immunology; Antimicrobial Cationic Peptides; anti‐neutrophil cytoplasmic antibodies; bactericidal/permeability‐increasing protein; Biological and medical sciences; Blood Proteins - immunology; Child; Child, Preschool; cystic fibrosis; Cystic Fibrosis - immunology; Cystic Fibrosis - microbiology; Cystic Fibrosis - physiopathology; Epitope Mapping; Errors of metabolism; Female; Humans; Immunoglobulin Isotypes - immunology; Male; Medical sciences; Membrane Proteins; Metabolic diseases; Middle Aged; Miscellaneous hereditary metabolic disorders; Original; Pseudomonas aeruginosa; Pseudomonas aeruginosa - immunology; Vasculitis - immunology; α1‐antitrypsin; Pseudomonadales; Human; Lung disease; Antineutrophil cytoplasmic antibody; Respiratory disease; Antibody; Pathogenesis; Lung; Autoantibody; Metabolic diseases; Permeability factor; Cystic fibrosis; α1-Antitrypsin; Genetic disease; Infection; Digestive diseases; Bacteria; Pseudomonadaceae; Complication; Pseudomonas aeruginosa; Pneumopathy; Pancreatic disease
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1046/j.1365-2249.1999.01006.x

Persistent infection with Pseudomonas aeruginosa and inflammatory mechanisms play an important role in cystic fibrosis (CF) lung disease. ANCA against BPI, a potent host defence protein with anti‐bacterial and anti‐endotoxin properties, have been described in CF. We have assessed the relationship of anti‐BPI antibodies to pulmonary disease severity in 148 CF subjects. IgA and IgG anti‐BPI antibodies were found in 55.4% and 70.3% of CF patients, respectively, and higher levels were strongly associated with colonization with P. aeruginosa (P = 0.001 and 0.039 for IgA and IgG antibodies, respectively). IgA and IgG anti‐BPI antibodies were independently associated with more severe lung disease as assessed by chest radiograph score (P = 0.023) and a significantly lower forced expiratory volume in 1 s (FEV1)% (P = 0.01). The pathophysiological relevance of the autoantibodies was investigated further by determining their epitope specificity and their effect on bacterial phagocytosis in vitro. Both isotypes of anti‐BPI antibodies were specific for the C‐terminus of BPI shown recently to be important for BPI‐mediated opsonization, and in vitro affinity‐purified anti‐BPI antibodies significantly reduced BPI‐induced phagocytosis of Escherichia coli compared with controls. These data indicate that anti‐BPI autoantibodies are associated with colonization with P. aeruginosa and worse lung disease in CF. The inhibition of bacterial phagocytosis suggests that these autoantibodies may contribute to the persistence of P. aeruginosa in the CF lung and so play a role in perpetuating CF lung damage.