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

Persistent infection with Pseudomonas aeruginosa and inflammatory mechanism s play an important role in cystic fibrosis (CF) lung disease. ANCA against BPI, a potent host defence protein with antibacterial and anti-endotoxin p roperties, have been described in CF. Pie 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, respect ively). 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 bacter ial phagocytosis in vitro. Both isotypes of anti-BPI antibodies were specif ic for the C-terminus of BPI shown recently to be important for BPI-mediate d opsonization, and in vitro affinity-purified anti-BPI antibodies signific antly reduced BPI-induced phagocytosis of Escherichia coli compared with co ntrols. These data indicate that anti-BPI autoantibodies are associated wit h colonization with P. aeruginosa and worse lung disease in CF. The inhibit ion of bacterial phagocytosis suggests that these autoantibodies may contri bute to the persistence of P. aeruginosa in the CF lung and so play a role in perpetuating CF lung damage.