Skip to main content
Journal of Clinical Microbiology logoLink to Journal of Clinical Microbiology
. 1992 Jul;30(7):1848–1855. doi: 10.1128/jcm.30.7.1848-1855.1992

Antibody responses to lipid A, core, and O sugars of the Pseudomonas aeruginosa lipopolysaccharide in chronically infected cystic fibrosis patients.

G Kronborg 1, A Fomsgaard 1, C Galanos 1, M A Freudenberg 1, N Høiby 1
PMCID: PMC265392  PMID: 1378455

Abstract

Enzyme-linked immunosorbent assays were developed separately for the three main parts of the Pseudomonas aeruginosa lipopolysaccharide (LPS) molecule, namely, lipid A, core, and O polysaccharide. Anti-lipid A, anticore, and anti-O polysaccharide antibodies were measured in serum samples from 12 patients with cystic fibrosis (CF) in a longitudinal study covering the period before P. aeruginosa infection was established through at least 5 years of chronic infection. The serum antibody response to all parts of the P. aeruginosa LPS molecule increased during the course of chronic infection. The increase in anti-lipid A antibodies was specific for P. aeruginosa lipid A, since no increase in anti-Escherichia coli lipid A antibodies was seen. Immunoglobulin G, A, and M (IgG, IgA and IgM) antibodies were all involved in the specific systemic response to P. aeruginosa lipid A, core, and the O polysaccharides. IgG and IgA levels in particular increased during the course of infection and were significantly higher than the antibody increase seen with age in a healthy control group. The local immune response in the lungs was investigated by measuring IgG, IgA, and IgM antibodies to the separate parts of the P. aeruginosa LPS molecule in sputum samples from 18 CF patients with at least a 5-year history of chronic P. aeruginosa infection. Antibodies detected in sputum were mainly anti-lipid A and anti-O polysaccharide antibodies of the IgG and IgA isotypes. Very high IgA anti-lipid A titers were detected in sputum samples from some CF patients.

Full text

PDF
1848

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Appelmelk B. J., Verweij-Van Vught A. M., MacLaren D. M., Thijs L. G. An enzyme-linked immunosorbent assay (ELISA) for the measurement of antibodies to different parts of the gram-negative lipopolysaccharide core region. J Immunol Methods. 1985 Oct 10;82(2):199–207. doi: 10.1016/0022-1759(85)90351-5. [DOI] [PubMed] [Google Scholar]
  2. Baltimore R. S., Christie C. D., Smith G. J. Immunohistopathologic localization of Pseudomonas aeruginosa in lungs from patients with cystic fibrosis. Implications for the pathogenesis of progressive lung deterioration. Am Rev Respir Dis. 1989 Dec;140(6):1650–1661. doi: 10.1164/ajrccm/140.6.1650. [DOI] [PubMed] [Google Scholar]
  3. Bhat R., Marx A., Galanos C., Conrad R. S. Structural studies of lipid A from Pseudomonas aeruginosa PAO1: occurrence of 4-amino-4-deoxyarabinose. J Bacteriol. 1990 Dec;172(12):6631–6636. doi: 10.1128/jb.172.12.6631-6636.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Brett M. M., Ghoneim A. T., Littlewood J. M. Prediction and diagnosis of early Pseudomonas aeruginosa infection in cystic fibrosis: a follow-up study. J Clin Microbiol. 1988 Aug;26(8):1565–1570. doi: 10.1128/jcm.26.8.1565-1570.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cross A. S., Sidberry H., Sadoff J. C. The human antibody response during natural bacteremic infection with gram-negative bacilli against lipopolysaccharide core determinants. J Infect Dis. 1989 Aug;160(2):225–236. doi: 10.1093/infdis/160.2.225. [DOI] [PubMed] [Google Scholar]
  6. Cryz S. J., Jr, Pitt T. L., Fürer E., Germanier R. Role of lipopolysaccharide in virulence of Pseudomonas aeruginosa. Infect Immun. 1984 May;44(2):508–513. doi: 10.1128/iai.44.2.508-513.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Engels W., Endert J., Kamps M. A., van Boven C. P. Role of lipopolysaccharide in opsonization and phagocytosis of Pseudomonas aeruginosa. Infect Immun. 1985 Jul;49(1):182–189. doi: 10.1128/iai.49.1.182-189.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Fahy J. V., Keoghan M. T., Crummy E. J., FitzGerald M. X. Bacteraemia and fungaemia in adults with cystic fibrosis. J Infect. 1991 May;22(3):241–245. doi: 10.1016/s0163-4453(05)80005-2. [DOI] [PubMed] [Google Scholar]
  9. Fomsgaard A. Antibodies to lipopolysaccharides: some diagnostic and protective aspects. APMIS Suppl. 1990;18:1–38. [PubMed] [Google Scholar]
  10. Fomsgaard A., Conrad R. S., Galanos C., Shand G. H., Høiby N. Comparative immunochemistry of lipopolysaccharides from typable and polyagglutinable Pseudomonas aeruginosa strains isolated from patients with cystic fibrosis. J Clin Microbiol. 1988 May;26(5):821–826. doi: 10.1128/jcm.26.5.821-826.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Fomsgaard A., Freudenberg M. A., Bendtzen K., Galanos C. Quantitation and biological activities of native tumour necrosis factor from LPS-stimulated human monocytes. APMIS. 1990 Jun;98(6):529–534. doi: 10.1111/j.1699-0463.1990.tb01067.x. [DOI] [PubMed] [Google Scholar]
  12. Fomsgaard A., Galanos C. Protective properties of a human IgG preparation rich in antibodies to a wide spectrum of lipopolysaccharides. APMIS. 1989 Dec;97(12):1114–1120. doi: 10.1111/j.1699-0463.1989.tb00525.x. [DOI] [PubMed] [Google Scholar]
  13. Fomsgaard A., Høiby N., Shand G. H., Conrad R. S., Galanos C. Longitudinal study of antibody response to lipopolysaccharides during chronic Pseudomonas aeruginosa lung infection in cystic fibrosis. Infect Immun. 1988 Sep;56(9):2270–2278. doi: 10.1128/iai.56.9.2270-2278.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Fomsgaard A., Zhang G. H., Shand G. H., Bendtzen K., Baek L. Immunochemical and biological reactivity of human anti-lipopolysaccharide IgG obtained by screening of blood donors. Scand J Immunol. 1989 Mar;29(3):309–316. doi: 10.1111/j.1365-3083.1989.tb01129.x. [DOI] [PubMed] [Google Scholar]
  15. Freudenberg M. A., Fomsgaard A., Mitov I., Galanos C. ELISA for antibodies to lipid A, lipopolysaccharides and other hydrophobic antigens. Infection. 1989 Sep-Oct;17(5):322–328. doi: 10.1007/BF01650719. [DOI] [PubMed] [Google Scholar]
  16. Freudenberg M. A., Galanos C. The metabolic fate of endotoxins. Prog Clin Biol Res. 1988;272:63–75. [PubMed] [Google Scholar]
  17. Galanos C., Jiao B. H., Komuro T., Freudenberg M. A., Lüderitz O. Large-scale fractionation of S-form lipopolysaccharide from Salmonella abortus equi. Chemical and serological characterization of the fractions. J Chromatogr. 1988 May 25;440:397–404. doi: 10.1016/s0021-9673(00)94543-6. [DOI] [PubMed] [Google Scholar]
  18. Galanos C., Lüderitz O., Westphal O. A new method for the extraction of R lipopolysaccharides. Eur J Biochem. 1969 Jun;9(2):245–249. doi: 10.1111/j.1432-1033.1969.tb00601.x. [DOI] [PubMed] [Google Scholar]
  19. Galanos C., Rietschel E. T., Lüderitz O., Westphal O. Interaction of lipopolysaccharides and lipid A with complement. Eur J Biochem. 1971 Mar 1;19(1):143–152. doi: 10.1111/j.1432-1033.1971.tb01298.x. [DOI] [PubMed] [Google Scholar]
  20. Hancock R. E., Mutharia L. M., Chan L., Darveau R. P., Speert D. P., Pier G. B. Pseudomonas aeruginosa isolates from patients with cystic fibrosis: a class of serum-sensitive, nontypable strains deficient in lipopolysaccharide O side chains. Infect Immun. 1983 Oct;42(1):170–177. doi: 10.1128/iai.42.1.170-177.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Jacobson M. A., Radolf J. D., Young L. S. Human IgG antibodies to Pseudomonas aeruginosa core lipopolysaccharide determinants are detected in chronic but not acute pseudomonas infection. Scand J Infect Dis. 1987;19(6):649–660. doi: 10.3109/00365548709117200. [DOI] [PubMed] [Google Scholar]
  22. 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]
  23. Kropinski A. M., Jewell B., Kuzio J., Milazzo F., Berry D. Structure and functions of Pseudomonas aeruginosa lipopolysaccharide. Antibiot Chemother (1971) 1985;36:58–73. doi: 10.1159/000410472. [DOI] [PubMed] [Google Scholar]
  24. Kulshin V. A., Zähringer U., Lindner B., Jäger K. E., Dmitriev B. A., Rietschel E. T. Structural characterization of the lipid A component of Pseudomonas aeruginosa wild-type and rough mutant lipopolysaccharides. Eur J Biochem. 1991 Jun 15;198(3):697–704. doi: 10.1111/j.1432-1033.1991.tb16069.x. [DOI] [PubMed] [Google Scholar]
  25. Mar P. J., Marget W., Schneider K., Belohradsky B. H., Roos R. Relevance of vesico-ureteric reflux in development of lipid A antibodies in recurrent urinary tract infections in children--a preliminary study. Eur J Pediatr. 1987 Jan;146(1):51–55. doi: 10.1007/BF00647284. [DOI] [PubMed] [Google Scholar]
  26. Ojeniyi B., Høiby N., Rosdahl V. T. Prevalence and persistence of polyagglutinable Pseudomonas aeruginosa in isolates from cystic fibrosis patients. APMIS. 1991 Feb;99(2):187–195. [PubMed] [Google Scholar]
  27. 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]
  28. Pier G. B., Markham R. B., Eardley D. Correlation of the biologic responses of C3H/HEJ mice to endotoxin with the chemical and structural properties of the lipopolysaccharides from Pseudomonas aeruginosa and Escherichia coli. J Immunol. 1981 Jul;127(1):184–191. [PubMed] [Google Scholar]
  29. Pier G. B., Thomas D. M. Characterization of the human immune response to a polysaccharide vaccine from Pseudomonas aeruginosa. J Infect Dis. 1983 Aug;148(2):206–213. doi: 10.1093/infdis/148.2.206. [DOI] [PubMed] [Google Scholar]
  30. Pitt T. L., MacDougall J., Penketh A. R., Cooke E. M. Polyagglutinating and non-typable strains of Pseudomonas aeruginosa in cystic fibrosis. J Med Microbiol. 1986 Mar;21(2):179–186. doi: 10.1099/00222615-21-2-179. [DOI] [PubMed] [Google Scholar]
  31. Rowe P. S., Meadow P. M. Structure of the Core oligosaccharide from the lipopolysaccharide of Pseudomonas aeruginosa PAC1R and its defective mutants. Eur J Biochem. 1983 May 2;132(2):329–337. doi: 10.1111/j.1432-1033.1983.tb07366.x. [DOI] [PubMed] [Google Scholar]
  32. Wood R. E., Boat T. F., Doershuk C. F. Cystic fibrosis. Am Rev Respir Dis. 1976 Jun;113(6):833–878. doi: 10.1164/arrd.1976.113.6.833. [DOI] [PubMed] [Google Scholar]
  33. Yokota S., Terashima M., Chiba J., Noguchi H. Variable cross-reactivity of Pseudomonas aeruginosa lipopolysaccharide-code-specific monoclonal antibodies and its possible relationship with serotype. J Gen Microbiol. 1992 Feb;138(2):289–296. doi: 10.1099/00221287-138-2-289. [DOI] [PubMed] [Google Scholar]
  34. Ziegler E. J., Fisher C. J., Jr, Sprung C. L., Straube R. C., Sadoff J. C., Foulke G. E., Wortel C. H., Fink M. P., Dellinger R. P., Teng N. N. Treatment of gram-negative bacteremia and septic shock with HA-1A human monoclonal antibody against endotoxin. A randomized, double-blind, placebo-controlled trial. The HA-1A Sepsis Study Group. N Engl J Med. 1991 Feb 14;324(7):429–436. doi: 10.1056/NEJM199102143240701. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Microbiology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES