Clinical role of autoantibody against bactericidal/permeability-increasing protein in chronic airway infection

Chronic airway infections often have persistent colonization of mucoid-derivative and/or biofilm-formed bacteria on the small airway surface. Such long-term colonization by bacteria sometimes induces harmful immune reactions in the host. Bactericidal/permeability-increasing protein (BPI) is one of the important agents in the phagocyte activity of neutrophils. An antineutrophil cytoplasmic autoantibody against BPI (BPI-ANCA) was recently detected. The clinical role of BPI-ANCA in 66 patients with chronic airway infections was investigated. Corresponding antigens in neutrophils against the antibody in their sera were observed by the indirect immunofluorescence method. After confiriming the antigen to be BPI, the presence of BPI-ANCA in their serum samples was determined by the enzyme-linked immunosorbent assay method. The titers were analyzed in relation to clinical symptoms, prognosis, and bacteriologic aspects, including in vitro examinations. Thirty-five of 66 samples (53%) were positive for cytoplasmic ANCA, and 48 cases (73%) were positive for serum BPI-ANCA. There were no positive cases among the sera samples of 7 healthy individuals. High titers of BPI-ANCA and a high frequency of BPI-positive indications were seen in cases with persistent colonization of gram-negative bacteria (P<0.05), and they also correlated with clinical symptoms and prognosis. In in vitro examinations, BPI-ANCA dose-dependently suppressed BPI that was induced by the interaction of neutrophils and gram-negative bacteria. BPI-ANCA is characteristically found in cronic infections, and it suppesses the BPI activity of neutrophils. An autoimmune manifestation such as this might increase the intractability of chronic airway infections.