Quantitative analysis of the IgG and IgG subclass immune responses to chromosomal Pseudomonas aeruginosa beta-lactamase in serum from patients with cystic fibrosis by western blotting and laser scanning densitometry

Background - Antibodies against chromosomal beta-lactamase of Pseudomonas aeruginosa (a beta ab) are markers of the development of resistance of P aeruginosa to beta-lactam antibiotics in patients with cystic fibrosis and chronic lung infection. The role of these antibodies in patients with chronic lung infection with P aeruginosa was further investigated by correlating the a beta ab IgG subclasses with pulmonary function in patients with cystic fibrosis. Methods - Immunoglobulin G (IgG) and IgG subclass a beta ab were investigated by western blotting and quantified by laser scanning densitometry. A longitudinal study on 43 consecutive patients with cystic fibrosis who developed chronic lung infection with P aeruginosa was performed. Results - IgG subclass a beta ab appeared in all patients with chronic infection with P aeruginosa. Eleven years after the onset of infection all the patients had IgG(1), 79% had IgG(4), 56% IgG(2), and only 16% of the patients had IgG(3) a beta ab. The IgG(1) and IgG(4) a beta ab appeared first, and more than 50% of the patients were IgG(1) and IgG(4) a beta ab positive within 2-3 years of the onset of infection, but IgG(2) positivity only appeared after seven years and IgG(3) remained absent from most of the patients, The median a beta ab levels increased during chronic infection: 100-fold for IgG(1), 22-fold for IgG(2), and 45-fold for IgG(4). A 16-fold increase in the IgG(3) a beta ab levels was detected in the six patients who developed IgG(3) a beta ab. In the first four years of the chronic infection the a beta ab titres were higher in patients with good lung function than in those with poor lung function. Conclusions - The association of a weak IgG(3) and a strong IgG(4) a beta ab response suggests that the contribution of a beta ab antibodies to lung diseases mediated by immune complexes might be less important than other antipseudomonal antibodies. A beneficial neutralising effect of the a beta ab antibodies on the antibiotic destroying enzymes may be an additional factor.