Abstract
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.
Full text
PDF





Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Chen H. Y., Yuan M., Ibrahim-Elmagboul I. B., Livermore D. M. National survey of susceptibility to antimicrobials amongst clinical isolates of Pseudomonas aeruginosa. J Antimicrob Chemother. 1995 Apr;35(4):521–534. doi: 10.1093/jac/35.4.521. [DOI] [PubMed] [Google Scholar]
- Chen H. Y., Yuan M., Livermore D. M. Mechanisms of resistance to beta-lactam antibiotics amongst Pseudomonas aeruginosa isolates collected in the UK in 1993. J Med Microbiol. 1995 Oct;43(4):300–309. doi: 10.1099/00222615-43-4-300. [DOI] [PubMed] [Google Scholar]
- Ciofu O., Giwercman B., Pedersen S. S., Høiby N. Development of antibiotic resistance in Pseudomonas aeruginosa during two decades of antipseudomonal treatment at the Danish CF Center. APMIS. 1994 Sep;102(9):674–680. [PubMed] [Google Scholar]
- Ciofu O., Giwercman B., Walter-Rasmussen J., Pressler T., Pedersen S. S., Høiby N. Antibodies against Pseudomonas aeruginosa chromosomal beta-lactamase inpatients with cystic fibrosis are markers of the development of resistance of P. aeruginosa to beta-lactams. J Antimicrob Chemother. 1995 Feb;35(2):295–304. doi: 10.1093/jac/35.2.295. [DOI] [PubMed] [Google Scholar]
- Giwercman B., Lambert P. A., Rosdahl V. T., Shand G. H., Høiby N. Rapid emergence of resistance in Pseudomonas aeruginosa in cystic fibrosis patients due to in-vivo selection of stable partially derepressed beta-lactamase producing strains. J Antimicrob Chemother. 1990 Aug;26(2):247–259. doi: 10.1093/jac/26.2.247. [DOI] [PubMed] [Google Scholar]
- Giwercman B., Meyer C., Lambert P. A., Reinert C., Høiby N. High-level beta-lactamase activity in sputum samples from cystic fibrosis patients during antipseudomonal treatment. Antimicrob Agents Chemother. 1992 Jan;36(1):71–76. doi: 10.1128/aac.36.1.71. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Giwercman B., Rasmussen J. W., Cioufu O., Clemmentsen I., Schumacher H., Høiby N. Antibodies against chromosomal beta-lactamase. Antimicrob Agents Chemother. 1994 Oct;38(10):2306–2310. doi: 10.1128/aac.38.10.2306. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Høiby N., Döring G., Schiøtz P. O. The role of immune complexes in the pathogenesis of bacterial infections. Annu Rev Microbiol. 1986;40:29–53. doi: 10.1146/annurev.mi.40.100186.000333. [DOI] [PubMed] [Google Scholar]
- Jefferis R., Reimer C. B., Skvaril F., de Lange G., Ling N. R., Lowe J., Walker M. R., Phillips D. J., Aloisio C. H., Wells T. W. Evaluation of monoclonal antibodies having specificity for human IgG sub-classes: results of an IUIS/WHO collaborative study. Immunol Lett. 1985;10(3-4):223–252. doi: 10.1016/0165-2478(85)90082-3. [DOI] [PubMed] [Google Scholar]
- Koch C., Høiby N. Pathogenesis of cystic fibrosis. Lancet. 1993 Apr 24;341(8852):1065–1069. doi: 10.1016/0140-6736(93)92422-p. [DOI] [PubMed] [Google Scholar]
- Kronborg G., Shand G. H., Fomsgaard A., Høiby N. Lipopolysaccharide is present in immune complexes isolated from sputum in patients with cystic fibrosis and chronic Pseudomonas aeruginosa lung infection. APMIS. 1992 Feb;100(2):175–180. [PubMed] [Google Scholar]
- Li X. Z., Ma D., Livermore D. M., Nikaido H. Role of efflux pump(s) in intrinsic resistance of Pseudomonas aeruginosa: active efflux as a contributing factor to beta-lactam resistance. Antimicrob Agents Chemother. 1994 Aug;38(8):1742–1752. doi: 10.1128/aac.38.8.1742. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Likavcanova E., Lagacé J. Quantitative analysis of immunoglobulin G subclass responses to Pseudomonas aeruginosa antigens in cystic fibrosis. J Med Microbiol. 1992 Jun;36(6):437–444. doi: 10.1099/00222615-36-6-437. [DOI] [PubMed] [Google Scholar]
- Livermore D. M. Clinical significance of beta-lactamase induction and stable derepression in gram-negative rods. Eur J Clin Microbiol. 1987 Aug;6(4):439–445. doi: 10.1007/BF02013107. [DOI] [PubMed] [Google Scholar]
- Mouton J. W., den Hollander J. G., Horrevorts A. M. Emergence of antibiotic resistance amongst Pseudomonas aeruginosa isolates from patients with cystic fibrosis. J Antimicrob Chemother. 1993 Jun;31(6):919–926. doi: 10.1093/jac/31.6.919. [DOI] [PubMed] [Google Scholar]
- O'Callaghan C. H., Morris A., Kirby S. M., Shingler A. H. Novel method for detection of beta-lactamases by using a chromogenic cephalosporin substrate. Antimicrob Agents Chemother. 1972 Apr;1(4):283–288. doi: 10.1128/aac.1.4.283. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pedersen S. S., Espersen F., Høiby N. Diagnosis of chronic Pseudomonas aeruginosa infection in cystic fibrosis by enzyme-linked immunosorbent assay. J Clin Microbiol. 1987 Oct;25(10):1830–1836. doi: 10.1128/jcm.25.10.1830-1836.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pedersen S. S., Koch C., Høiby N., Rosendal K. An epidemic spread of multiresistant Pseudomonas aeruginosa in a cystic fibrosis centre. J Antimicrob Chemother. 1986 Apr;17(4):505–516. doi: 10.1093/jac/17.4.505. [DOI] [PubMed] [Google Scholar]
- Pressler T., Pedersen S. S., Espersen F., Høiby N., Koch C. IgG subclass antibodies to Pseudomonas aeruginosa in sera from patients with chronic Ps. aeruginosa infection investigated by ELISA. Clin Exp Immunol. 1990 Sep;81(3):428–434. doi: 10.1111/j.1365-2249.1990.tb05351.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pressler T., Pedersen S. S., Espersen F., Høiby N., Koch C. IgG subclass antibody responses to alginate from Pseudomonas aeruginosa in patients with cystic fibrosis and chronic P. aeruginosa infection. Pediatr Pulmonol. 1992 Sep;14(1):44–51. doi: 10.1002/ppul.1950140109. [DOI] [PubMed] [Google Scholar]
- Sanders C. C., Sanders W. E., Jr Clinical importance of inducible beta-lactamases in gram-negative bacteria. Eur J Clin Microbiol. 1987 Aug;6(4):435–438. doi: 10.1007/BF02013106. [DOI] [PubMed] [Google Scholar]
- Schaad U. B., Lang A. B., Wedgwood J., Buehlamnn U., Fuerer E. Serotype-specific serum IgG antibodies to lipopolysaccharides of Pseudomonas aeruginosa in cystic fibrosis: correlation to disease, subclass distribution, and experimental protective capacity. Pediatr Res. 1990 May;27(5):508–513. doi: 10.1203/00006450-199005000-00019. [DOI] [PubMed] [Google Scholar]
- Shand G. H., Pedersen S. S., Tilling R., Brown M. R., Høiby N. Use of immunoblot detection of serum antibodies in the diagnosis of chronic Pseudomonas aeruginosa lung infection in cystic fibrosis. J Med Microbiol. 1988 Nov;27(3):169–177. doi: 10.1099/00222615-27-3-169. [DOI] [PubMed] [Google Scholar]
- Towbin H., Staehelin T., Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350–4354. doi: 10.1073/pnas.76.9.4350. [DOI] [PMC free article] [PubMed] [Google Scholar]
- van der Zee J. S., van Swieten P., Aalberse R. C. Inhibition of complement activation by IgG4 antibodies. Clin Exp Immunol. 1986 May;64(2):415–422. [PMC free article] [PubMed] [Google Scholar]
- van der Zee J. S., van Swieten P., Aalberse R. C. Serologic aspects of IgG4 antibodies. II. IgG4 antibodies form small, nonprecipitating immune complexes due to functional monovalency. J Immunol. 1986 Dec 1;137(11):3566–3571. [PubMed] [Google Scholar]

