Abstract
A total of 89 patients at risk for, or with invasive aspergillosis (IA) were recruited from bone marrow transplantation (BMT) units in two Lisbon hospitals, and followed for 2½ years to monitor their immune response. Of these patients, six developed probable IA, from which five died. The presence of serum IgG or IgA antibodies against seven Aspergillus recombinant antigens was assessed in patients with IA, using an enzyme‐linked immunosorbent assay (ELISA). In parallel, the serum levels of galactomannan (GM) were also monitored, using the Platelia Aspergillus kit (Sanofi Pasteur, Marnes‐la‐Coquette, France). Superoxide dismutase (Sod) and 94 kDa were the most immunogenic antigens for IgA, while the IgG pattern of recognition changed from patient to patient. From our results we conclude that although follow‐up of antibodies against these antigens should not be used as a diagnostic method, patients with IA do produce an immune response that may influence disease outcome. J. Clin. Lab. Anal. 16:156–162, 2002. © 2002 Wiley‐Liss, Inc.
Keywords: Aspergillus, IgG, IgA, ELISA
REFERENCES
- 1. Patterson TF, Kirkpatrick WR, White M, et al. 2000. Invasive aspergillosis. Disease spectrum, treament practices, and outcomes. I3 Aspergillus study groups. Medicine (Balt) 79:250–260. [DOI] [PubMed] [Google Scholar]
- 2. Cordonnier C, Groupe CLIOH. 1996. Réflexions sur la prophylaxie de l’aspergillose en onco‐hématologie. Hématologie 2:262–266. [Google Scholar]
- 3. Derouin F. 1994. Special issue on aspergillosis. Pathol Biol 42:625–736. [PubMed] [Google Scholar]
- 4. Patel R, Paya CV. 1997. Infections in solid‐organ transplant recipients. Clin Microbiol Rev 10:86–124. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5. Salonen J, Nikoskelainen J. 1993. Lethal infections in patients with haematological malignancies. Eur J Haematol 51:102–108. [DOI] [PubMed] [Google Scholar]
- 6. Kami M, Tanaka Y, Kanda Y, et al. 2000. Computed tomographic scan of the chest, (1→3)‐β‐D‐glucan assay in early diagnosis of invasive pulmonary aspergillosis: a prospective study of 215 patients. Haematologica 85:754–752. [PubMed] [Google Scholar]
- 7. Aisner J, Schimpff S, Wiernik PH. 1991. Treatment of invasive aspergillosis: relation to early diagnosis and therapy. Ann Intern Med 86:539–543. [DOI] [PubMed] [Google Scholar]
- 8. Denning DW. 1996. Therapeutic outcome in invasive aspergillosis. Clin Infect Dis 23:608–614. [DOI] [PubMed] [Google Scholar]
- 9. Denning DW, Stevens DA. 1990. Antifungal and surgical treatment of invasive aspergillosis: review of 2,121 published cases. Rev Infect Dis 12:1147–1201. [DOI] [PubMed] [Google Scholar]
- 10. Maertens J, Verhaegen J, Demuynck H, et al. 1999. Autopsy‐controlled prospective evaluation of serial screening for circulating galactomannan by a sandwich enzyme‐linked immunosorbent assay for haematological patients at risk for invasive aspergillosis. J Clin Microbiol 37:3223–3228. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11. Bretagne S, Marmorat‐Khuong A, Kuentz M, Latgé JP, Bart‐Delabasse E, Cordonnier C. 1997. Serum Aspergillus galactomannan antigen testing by sandwich ELISA: pratical use in neutropenic patients. J Infect 35:7–15. [DOI] [PubMed] [Google Scholar]
- 12. Patterson TF, Miniter P, Ryan JL, Andriole V. 1995. Aspergillus antigen detection in the diagnosis of invasive aspergillosis. J Infect Dis 171:1553–1558. [DOI] [PubMed] [Google Scholar]
- 13. Van Cutsen J, Meulemans L, Van Gerven F, Stynen D. 1993. Effect of tissue invasion and treatment with itraconazole or amphotericin B on galactomannan levels in plasma of guinea‐pigs with experimental invasive aspergillosis. J Med Vet Mycol 31:315–324. [Google Scholar]
- 14. Maertens J, Verhaegen J, Lagrou K, Van Eldere J, Boogaerts M. 2001. Screening for circulating galactomannan as a noninvasive diagnostic tool for invasive aspergillosis in prolonged neutropenic patients and stem cell transplantation recipients: a prospective validation. Blood 97:1604–1610. [DOI] [PubMed] [Google Scholar]
- 15. Bodey G, Bueltman B, Duguid W, et al. 1992. Fungal infections in cancer patients: an international autopsy survey. Eur J Clin Microbiol Infect Dis 11:99–109. [DOI] [PubMed] [Google Scholar]
- 16. Denning DW. 1995. Issues in the management of invasive aspergillosis. Ann Med Intern 146:106–110. [PubMed] [Google Scholar]
- 17. Groll AH, Shah PM, Mentzel C, Schneider M, Just‐Nuebling G, Huebner K. 1996. Trends in the postmortem epidemiology of invasive fungal infections at a university hospital. J Infect 33:23–32. [DOI] [PubMed] [Google Scholar]
- 18. Verweij PE, Denning DW. 1997. Diagnostic and therapeutic strategies for invasive aspergillosis. Respir Crit Care 18:203–215. [Google Scholar]
- 19. Denning DW. 1998. Invasive aspergillosis. Clin Infect Dis 26:781–805. [DOI] [PubMed] [Google Scholar]
- 20. McWhinney PH, Kibbler CC, Hamon MD, et al. 1993. Progress in the diagnosis and management of aspergillosis in bone marrow transplantation: 13 years’ experience. Clin Infect Dis 17:397–404. [DOI] [PubMed] [Google Scholar]
- 21. Ribaud P, Chastang C, Latgé JP, et al. 1999. Survival and prognostic factors of invasive aspergillosis after allogeneic bone marrow transplantation. Clin Infect Dis 28:322–330. [DOI] [PubMed] [Google Scholar]
- 22. Wald A, Leisenring W, Van Burik JA, Bowden RA. 1997. Epidemiology of Aspergillus infections in a large cohort of patients undergoing bone marrow transplantation. J Infect Dis 175:1459–1466. [DOI] [PubMed] [Google Scholar]
- 23. Walsh TJ, De Pauw B, Anaissie E, Martino P. 1994. Recent advances in the epidemiology, prevention and treatment of invasive fungal infections in neutropenic patients. J Med Vet Mycol 32(Suppl 1):33–51. [DOI] [PubMed] [Google Scholar]
- 24. Manso E, Montillo M, Desio G, Damico S, Discepoli G, Leoni P. 1994. Value of antigen and antibody detection in the serological diagnosis of invasive aspergillosis in patients with haematological malignancies. Eur J Clin Microbiol Infect Dis 13:756–760. [DOI] [PubMed] [Google Scholar]
- 25. Stynen D, Goris A, Sarfati J, Latgé JP. 1995. A new sensitive sandwich enzyme‐lynked immunosorbent assay to detect galactofuran in patients with invasive aspergillosis. J Clin Microbiol 33:497–500. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26. Suhalian A, Tabouret M, Ribaud P, et al. 1996. Comparison of an enzyme immunoassay and latex agglutination test for detection of galactomannan in the diagnosis of invasive aspergillosis. Eur J Clin Microbiol Infect Dis 15:139–145. [DOI] [PubMed] [Google Scholar]
- 27. Verweij PE, Erjavec Z, Sluiters W, et al. 1998. Detection of antigen in sera of patients with invasive aspergillosis: intra‐ and inter‐laboratory reproducibility. J Clin Microbiol 36:1612–1616. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28. Barnes RA. 1993. Aspergillus infection: does serodiagnosis work? Serodiagn Immunother Infect Dis 5:135–138. [Google Scholar]
- 29. De Repentigny L. 1989. Serological techniques for diagnosis of fungal infection. Eur J Clin Microbiol Infect Dis 4:362–375. [DOI] [PubMed] [Google Scholar]
- 30. Fratamico PM, Buckley HR. 1991. Identification and characterisation of an immunodominant 58‐kilodalton antigen of Aspergillus fumigatus recognized by sera of patients with invasive aspergillosis. Infect Immunol 59:309–315. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 31. Hearn VM, Pinel C, Blachier S, Ambroise‐Thomas P, Grillot R. 1995. Specific antibody detection in invasive aspergillosis by analytical isoelectrofocusing and immunoblotting methods. J Clin Microbiol 33:982–986. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 32. Kappe RA, Schulze‐Berge A, Sonntag HG. 1996. Evaluation of eight antibody tests and one antigen test for the diagnosis of invasive aspergillosis. Mycoses 39:13–23. [DOI] [PubMed] [Google Scholar]
- 33. Matthews R, Burnie JP, Fox A, Tabaqchali S. 1985. Immunoblot analysis of serological responses in invasive aspergillosis. J Clin Pathol 38:1300–1303. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 34. Beauvais A, Monod M, Wyniger J, et al. 1997. Dipeptidil‐peptidase IV secreted by Aspergillus fumigatus, a fungus pathogenic to humans. Infect Immunol 67:3042–3047. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 35. Latgé JP. 1999. Aspergillus fumigatus and aspergillosis. Clin Microbiol Rev 12:310–350. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 36. Beauvais A, Monod M, Debeaupuis JP, Diaquin M, Kobayashi H, Latgé JP. 1997. Biochemical and antigenic characterization of a new dipeptidil‐peptidase isolated from Aspergillus fumigatus . J Biol Chem 272:6238–6244. [DOI] [PubMed] [Google Scholar]
