Skip to main content
NCBI home page
Thorax logoLink to Thorax
. 1999 Jan;54(1):44–50. doi: 10.1136/thx.54.1.44

Specific IgG subclass antibody pattern to Aspergillus fumigatus in patients with cystic fibrosis with allergic bronchopulmonary aspergillosis (ABPA)

M Skov 1, T Pressler 1, H Jensen 1, N Hoiby 1, C Koch 1
PMCID: PMC1745361  PMID: 10343631

Abstract

BACKGROUND—IgG and IgG subclass antibodies to Aspergillus fumigatus (A fumigatus) were measured in a large population of patients with cystic fibrosis to elucidate a putative antibody pattern specific for allergic bronchopulmonary aspergillosis (ABPA).
METHODS—An ELISA technique using water soluble somatic hyphal (WSSH) A fumigatus antigens and subclass specific monoclonal antibodies was used for cross sectional quantification of IgG and IgG1-4 subclass antibody levels in the serum of 238 patients with cystic fibrosis and 107 healthy controls.
RESULTS—In patients with cystic fibrosis persistently colonised with A fumigatus the subclass antibody levels were significantly increased compared with patients with cystic fibrosis never or rarely colonised (p<0.001). The group of patients persistently colonised with A fumigatus with ABPA (+Af+ABPA) had significantly increased levels of IgG antibodies to A fumigatus (Af-IgG) (median 69 ELISA units (EU) versus 31) and of subclasses Af-IgG1 (91 versus 27), Af-IgG2 (143 versus 56), and Af-IgG4 antibodies (72 versus 20), but not of IgG3 (17 versus 15), compared with the colonised patients without ABPA (+Af-ABPA). Patients with cystic fibrosis with no or only rare isolates of A fumigatus without ABPA (-Af-ABPA) also had significantly increased subclass antibody levels (Af-IgG1 9 versus 3, Af-IgG2 28 versus 5, Af-IgG4 16 versus 4; p<0.001) compared with healthy controls. Low, although detectable, levels of antibodies were demonstrated in healthy controls. ABPA seemed to occur independently of Pseudomonas aeruginosa infection. Using diagnostic cut off levels for ABPA, sensitivity and specificity were calculated. The highest specificity was found for IgG4 (88%); sensitivity was between 65% and 73%. The positive predictive values (PPV) were moderate, whereas the negative predictive values (NPV) were high (96% in all subclasses except IgG3 with 94%). PPV increased to 50% if IgG1 as well as IgG2 and IgG4 were included.
CONCLUSIONS—In a large number of unselected patients with cystic fibrosis significantly increased levels of Af-specific antibodies belonging to total IgG and all four subclasses were found in all groups of patients compared with healthy controls. In patients persistently colonised with A fumigatus these levels were significantly higher than in non-colonised patients, and the significantly highest levels (with the exception of IgG3) were found in patients with ABPA. Using a sensitive ELISA technique, measurements of IgG and IgG subclass antibodies to A fumigatus might be of importance in the management of ABPA, especially as a screening test to exclude the presence of ABPA; other tests are needed to confirm the diagnosis.



Full Text

The Full Text of this article is available as a PDF (154.6 KB).

Selected References

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

  1. Forsgren A., Sjöquist J. "Protein A" from S. aureus. I. Pseudo-immune reaction with human gamma-globulin. J Immunol. 1966 Dec;97(6):822–827. [PubMed] [Google Scholar]
  2. Forsyth K. D., Hohmann A. W., Martin A. J., Bradley J. IgG antibodies to Aspergillus fumigatus in cystic fibrosis: a laboratory correlate of disease activity. Arch Dis Child. 1988 Aug;63(8):953–957. doi: 10.1136/adc.63.8.953. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Greenberger P. A., Miller T. P., Roberts M., Smith L. L. Allergic bronchopulmonary aspergillosis in patients with and without evidence of bronchiectasis. Ann Allergy. 1993 Apr;70(4):333–338. [PubMed] [Google Scholar]
  4. Greenberger P. A., Patterson R. Application of enzyme-linked immunosorbent assay (ELISA) in diagnosis of allergic bronchopulmonary aspergillosis. J Lab Clin Med. 1982 Feb;99(2):288–293. [PubMed] [Google Scholar]
  5. Hoiby N. Pseudomonas aeruginosa infection in cystic fibrosis. Diagnostic and prognostic significance of pseudomonas aeruginosa precipitins determined by means of crossed immunoelectrophoresis. A survey. Acta Pathol Microbiol Scand Suppl. 1977;(262):1–96. [PubMed] [Google Scholar]
  6. Jensen H. E., Halbaek B., Lind P., Krogh H. V., Frandsen P. L. Development of murine monoclonal antibodies for the immunohistochemical diagnosis of systemic bovine aspergillosis. J Vet Diagn Invest. 1996 Jan;8(1):68–75. doi: 10.1177/104063879600800111. [DOI] [PubMed] [Google Scholar]
  7. Knutsen A. P., Mueller K. R., Hutcheson P. S., Slavin R. G. Serum anti-Aspergillus fumigatus antibodies by immunoblot and ELISA in cystic fibrosis with allergic bronchopulmonary aspergillosis. J Allergy Clin Immunol. 1994 May;93(5):926–931. doi: 10.1016/0091-6749(94)90387-5. [DOI] [PubMed] [Google Scholar]
  8. Kurup V. P., Resnick A., Kalbfleish J., Fink J. N. Antibody isotype responses in Aspergillus-induced diseases. J Lab Clin Med. 1990 Mar;115(3):298–303. [PubMed] [Google Scholar]
  9. Leser C., Kauffman H. F., Virchow C., Sr, Menz G. Specific serum immunopatterns in clinical phases of allergic bronchopulmonary aspergillosis. J Allergy Clin Immunol. 1992 Oct;90(4 Pt 1):589–599. doi: 10.1016/0091-6749(92)90131-k. [DOI] [PubMed] [Google Scholar]
  10. Leung P. S., Gershwin M. E., Coppel R., Halpern G., Novey H., Castles J. J. Localization, molecular weight and immunoglobulin subclass response to Aspergillus fumigatus allergens in acute bronchopulmonary aspergillosis. Int Arch Allergy Appl Immunol. 1988;85(4):416–421. doi: 10.1159/000234544. [DOI] [PubMed] [Google Scholar]
  11. Nelson L. A., Callerame M. L., Schwartz R. H. Aspergillosis and atopy in cystic fibrosis. Am Rev Respir Dis. 1979 Oct;120(4):863–873. doi: 10.1164/arrd.1979.120.4.863. [DOI] [PubMed] [Google Scholar]
  12. Nikolaizik W. H., Moser M., Crameri R., Little S., Warner J. O., Blaser K., Schöni M. H. Identification of allergic bronchopulmonary aspergillosis in cystic fibrosis patients by recombinant Aspergillus fumigatus I/a-specific serology. Am J Respir Crit Care Med. 1995 Aug;152(2):634–639. doi: 10.1164/ajrccm.152.2.7633719. [DOI] [PubMed] [Google Scholar]
  13. 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]
  14. Pressler T., Mansa B., Jensen T., Pedersen S. S., Høiby N., Koch C. Increased IgG2 and IgG3 concentration is associated with advanced Pseudomonas aeruginosa infection and poor pulmonary function in cystic fibrosis. Acta Paediatr Scand. 1988 Jul;77(4):576–582. doi: 10.1111/j.1651-2227.1988.tb10703.x. [DOI] [PubMed] [Google Scholar]
  15. 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]
  16. Schønheyder H., Andersen P., Stenderup A. Serum antibodies to aspergillus fumigatus in patients with pulmonary aspergillosis detected by immunofluorescence. Acta Pathol Microbiol Immunol Scand B. 1982 Aug;90(4):273–279. doi: 10.1111/j.1699-0463.1982.tb00118.x. [DOI] [PubMed] [Google Scholar]
  17. Schønheyder H., Jensen T., Høiby N., Andersen P., Koch C. Frequency of Aspergillus fumigatus isolates and antibodies to aspergillus antigens in cystic fibrosis. Acta Pathol Microbiol Immunol Scand B. 1985 Apr;93(2):105–112. doi: 10.1111/j.1699-0463.1985.tb02860.x. [DOI] [PubMed] [Google Scholar]
  18. Tomee J. F., Dubois A. E., Koëter G. H., Beaumont F., van der Werf T. S., Kauffman H. F. Specific IgG4 responses during chronic and transient antigen exposure in aspergillosis. Am J Respir Crit Care Med. 1996 Jun;153(6 Pt 1):1952–1957. doi: 10.1164/ajrccm.153.6.8665060. [DOI] [PubMed] [Google Scholar]
  19. Trompelt J., Becker W. M., Schlaak M. Analysis of IgG subclass and IgE response in allergic disease caused by Aspergillus fumigatus by immunoblotting techniques. Int Arch Allergy Immunol. 1994 Aug;104(4):390–398. doi: 10.1159/000236697. [DOI] [PubMed] [Google Scholar]
  20. Wide L., Bennich H., Johansson S. G. Diagnosis of allergy by an in-vitro test for allergen antibodies. Lancet. 1967 Nov 25;2(7526):1105–1107. doi: 10.1016/s0140-6736(67)90615-0. [DOI] [PubMed] [Google Scholar]
  21. Wilson E. V., Hearn V. M. Use of Aspergillus fumigatus mycelial antigens in enzyme-linked immunosorbent assay and counter-immunoelectrophoresis. J Med Microbiol. 1983 Feb;16(1):97–105. doi: 10.1099/00222615-16-1-97. [DOI] [PubMed] [Google Scholar]
  22. Workshop on experimental methodology for clinical studies of adverse reactions to foods and food additives. J Allergy Clin Immunol. 1990 Sep;86(3 Pt 2):421–442. doi: 10.1016/s0091-6749(05)80252-0. [DOI] [PubMed] [Google Scholar]
  23. el-Dahr J. M., Fink R., Selden R., Arruda L. K., Platts-Mills T. A., Heymann P. W. Development of immune responses to Aspergillus at an early age in children with cystic fibrosis. Am J Respir Crit Care Med. 1994 Dec;150(6 Pt 1):1513–1518. doi: 10.1164/ajrccm.150.6.7952609. [DOI] [PubMed] [Google Scholar]

Articles from Thorax are provided here courtesy of BMJ Publishing Group

RESOURCES