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 IgG1, 79% had IgG4, 56% IgG2, and only 16% of the patients had IgG3 a beta ab. The IgG1 and IgG4 a beta ab appeared first, and more than 50% of the patients were IgG1 and IgG4 a beta ab positive within 2-3 years of the onset of infection, but IgG2 positivity only appeared after seven years and IgG3 remained absent from most of the patients. The median a beta ab levels increased during chronic infection: 100-fold for IgG1, 22-fold for IgG2, and 45-fold for IgG4. A 16-fold increase in the IgG3 a beta ab levels was detected in the six patients who developed IgG3 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 IgG3 and a strong IgG4 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.
Petersen
T D
TD
Institute of Medical Microbiology and Immunology, Rigshospitalet Copenhagen, Denmark.
Ciofu
O
O
Pressler
T
T
Giwercman
B
B
Pedersen
S S
SS
Høiby
N
N
D000293:Adolescent; D000328:Adult; D000900:Anti-Bacterial Agents; D015153:Blotting, Western; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D003550:Cystic Fibrosis / Q000150:complications / Q000276:immunology / Q000382:microbiology*; D003720:Densitometry; D004352:Drug Resistance, Microbial; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D007223:Infant; D008137:Longitudinal Studies; D008875:Middle Aged; D011552:Pseudomonas Infections / Q000150:complications / Q000201:enzymology* / Q000276:immunology; D011550:Pseudomonas aeruginosa; D012129:Respiratory Function Tests; D001618:beta-Lactamases / Q000276:immunology*; D047090:beta-Lactams
D000900:Anti-Bacterial Agents; D007074:Immunoglobulin G; D047090:beta-Lactams; D001618:beta-Lactamases