Skip to main content
PMC home page
Infection and Immunity logoLink to Infection and Immunity
. 1991 Jul;59(7):2434–2446. doi: 10.1128/iai.59.7.2434-2446.1991

Antigen complex of Coccidioides immitis which elicits a precipitin antibody response in patients.

G T Cole 1, D Kruse 1, K R Seshan 1
PMCID: PMC258029  PMID: 2050408

Abstract

The occurrence in patients of elevated levels of immunoglobulin M (IgM) precipitin antibody to Coccidioides immitis antigens, which are commonly detected by the immunodiffusion-tube precipitin (TP) assay, is suggestive of primary nondisseminating coccidioidomycosis. We previously demonstrated that the concanavalin A-bound mycelial culture filtrate plus lysate preparation is a source of at least two TP antibody-reactive antigens (TP-Ags), which were identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis as 120- and 110-kDa fractions. Evidence is presented here that the crude filtrate plus lysate preparation contains additional lectin-bound, TP antibody-reactive fractions as well as a component which elicits a complement fixation antibody response in patients. The 120- and 110-kDa fractions were isolated from the antigen complex and further characterized in this paper. Both TP-Ags are glycoproteins and have been shown by immunoelectron microscopy to be colocalized within cytoplasmic vesicles and the wall of spherules. Deglycosylation of these TP-Ags by sodium periodate treatment resulted in a loss in patients of 82 to 95% of IgM adsorption to the antigens as detected by the enzyme-linked immunosorbent assay (ELISA). Comparison of their carbohydrate compositions revealed that mannose and glucose are the predominant monosaccharides of both TP-Ags but only the 120-kDa fraction contained 3-O-methylmannose, a sugar which appears to be unique to C. immitis among the systemic fungal pathogens. We previously showed that 3-O-methylmannose is at least partly responsible for the reactivity of IgM antibody with the 120-kDa TP-Ag. Good correlation was shown between results of immunodiffusion-TP assays and ELISAs of IgM response to both the 120- and 110-kDa fractions by using 70 serum samples from patients with proved coccidioidomycosis. However, only 2.8% (3 of 109) of the serum samples from patients with other mycoses and nonmycotic infections showed IgM adsorption to the 120-kDa TP-Ag as detected by the ELISA, while 21.1% (23 of 109) showed IgM adsorption to the 110-kDa TP-Ag. The 120-kDa TP-Ag is a potentially valuable serodiagnostic reagent for detection of specific IgM by ELISA in patients with primary coccidioidomycosis.

Full text

PDF
2443

Images in this article

2437Image
on p.2437
2438Image
on p.2438
2438Image
on p.2438
2442Image
on p.2442
2443Image
on p.2443
2444Image
on p.2444

Selected References

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

  1. Ampel N. M., Wieden M. A., Galgiani J. N. Coccidioidomycosis: clinical update. Rev Infect Dis. 1989 Nov-Dec;11(6):897–911. doi: 10.1093/clinids/11.6.897. [DOI] [PubMed] [Google Scholar]
  2. Calhoun D. L., Osir E. O., Dugger K. O., Galgiani J. N., Law J. H. Humoral antibody responses to specific antigens of Coccidioides immitis. J Infect Dis. 1986 Aug;154(2):265–272. doi: 10.1093/infdis/154.2.265. [DOI] [PubMed] [Google Scholar]
  3. Cassone A., Torosantucci A., Boccanera M., Pellegrini G., Palma C., Malavasi F. Production and characterisation of a monoclonal antibody to a cell-surface, glucomannoprotein constituent of Candida albicans and other pathogenic Candida species. J Med Microbiol. 1988 Dec;27(4):233–238. doi: 10.1099/00222615-27-4-233. [DOI] [PubMed] [Google Scholar]
  4. Cole G. T., Kirkland T. N., Franco M., Zhu S., Yuan L., Sun S. H., Hearn V. M. Immunoreactivity of a surface wall fraction produced by spherules of Coccidioides immitis. Infect Immun. 1988 Oct;56(10):2695–2701. doi: 10.1128/iai.56.10.2695-2701.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cole G. T., Kruse D., Zhu S. W., Seshan K. R., Wheat R. W. Composition, serologic reactivity, and immunolocalization of a 120-kilodalton tube precipitin antigen of Coccidioides immitis. Infect Immun. 1990 Jan;58(1):179–188. doi: 10.1128/iai.58.1.179-188.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cole G. T., Seshan K. R., Franco M., Bukownik E., Sun S. H., Hearn V. M. Isolation and morphology of an immunoreactive outer wall fraction produced by spherules of Coccidioides immitis. Infect Immun. 1988 Oct;56(10):2686–2694. doi: 10.1128/iai.56.10.2686-2694.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Cole G. T., Zhu S. W., Pan S. C., Yuan L., Kruse D., Sun S. H. Isolation of antigens with proteolytic activity from Coccidioides immitis. Infect Immun. 1989 May;57(5):1524–1534. doi: 10.1128/iai.57.5.1524-1534.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Cox R. A., Britt L. A. Antigenic identity of biologically active antigens in coccidioidin and spherulin. Infect Immun. 1987 Nov;55(11):2590–2596. doi: 10.1128/iai.55.11.2590-2596.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Dolan M. J., Cox R. A., Williams V., Woolley S. Development and characterization of a monoclonal antibody against the tube precipitin antigen of Coccidioides immitis. Infect Immun. 1989 Apr;57(4):1035–1039. doi: 10.1128/iai.57.4.1035-1039.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Galgiani J. N., Dugger K. O., Ampel N. M., Sun S. H., Law J. H. Extraction of serologic and delayed hypersensitivity antigens from spherules of Coccidioides immitis. Diagn Microbiol Infect Dis. 1988 Oct;11(2):65–80. doi: 10.1016/0732-8893(88)90075-2. [DOI] [PubMed] [Google Scholar]
  11. Huppert M., Adler J. P., Rice E. H., Sun S. H. Common antigens among systemic disease fungi analyzed by two-dimensional immunoelectrophoresis. Infect Immun. 1979 Feb;23(2):479–485. doi: 10.1128/iai.23.2.479-485.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kruse D., Cole G. T. Isolation of tube precipitin antibody-reactive fractions of Coccidioides immitis. Infect Immun. 1990 Jan;58(1):169–178. doi: 10.1128/iai.58.1.169-178.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Lo C. Y., Notenboom R. H. A new enzyme immunoassay specific for blastomycosis. Am Rev Respir Dis. 1990 Jan;141(1):84–88. doi: 10.1164/ajrccm/141.1.84. [DOI] [PubMed] [Google Scholar]
  14. Millette C. F., Scott B. K. Identification of spermatogenic cell plasma membrane glycoproteins by two-dimensional electrophoresis and lectin blotting. J Cell Sci. 1984 Jan;65:233–248. doi: 10.1242/jcs.65.1.233. [DOI] [PubMed] [Google Scholar]
  15. PAPPAGIANIS D., LINDSEY N. J., SMITH C. E., SAITO M. T. ANTIBODIES IN HUMAN COCCIDIOIDOMYCOSIS: IMMUNOELECTROPHORETIC PROPERTIES. Proc Soc Exp Biol Med. 1965 Jan;118:118–122. doi: 10.3181/00379727-118-29773. [DOI] [PubMed] [Google Scholar]
  16. PAPPAGIANIS D., SMITH C. E., KOBAYASHI G. S., SAITO M. T. Studies of antigens from young mycelia of Coccidioides immitis. J Infect Dis. 1961 Jan-Feb;108:35–44. doi: 10.1093/infdis/108.1.35. [DOI] [PubMed] [Google Scholar]
  17. Pappagianis D., Zimmer B. L. Serology of coccidioidomycosis. Clin Microbiol Rev. 1990 Jul;3(3):247–268. doi: 10.1128/cmr.3.3.247. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Raman C., Khardori N., Von Behren L. A., Wheat L. J., Tewari R. P. Evaluation of an ELISA for the detection of anti-Histoplasma ribosomal and antihistoplasmin antibodies in histoplasmosis. J Clin Lab Anal. 1990;4(3):199–207. doi: 10.1002/jcla.1860040311. [DOI] [PubMed] [Google Scholar]
  19. Resnick S., Pappagianis D., McKerrow J. H. Proteinase production by the parasitic cycle of the pathogenic fungus Coccidioides immitis. Infect Immun. 1987 Nov;55(11):2807–2815. doi: 10.1128/iai.55.11.2807-2815.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Resnick S., Zimmer B., Pappagianis D., Eakin A., McKerrow J. Purification and amino-terminal sequence analysis of the complement-fixing and precipitin antigens from Coccidioides immitis. J Clin Microbiol. 1990 Feb;28(2):385–388. doi: 10.1128/jcm.28.2.385-388.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. SALVIN S. B. Current concepts of diagnostic serology and skin hypersensitivity in the mycoses. Am J Med. 1959 Jul;27(1):97–114. doi: 10.1016/0002-9343(59)90064-6. [DOI] [PubMed] [Google Scholar]
  22. SMITH C. E., SAITO M. T., BEARD R. R., KEPP R. M., CLARK R. W., EDDIE B. U. Serological tests in the diagnosis and prognosis of coccidioidomycosis. Am J Hyg. 1950 Jul;52(1):1–21. doi: 10.1093/oxfordjournals.aje.a119404. [DOI] [PubMed] [Google Scholar]
  23. SMITH C. E., SAITO M. T., SIMONS S. A. Pattern of 39,500 serologic tests in coccidioidomycosis. J Am Med Assoc. 1956 Feb 18;160(7):546–552. doi: 10.1001/jama.1956.02960420026008. [DOI] [PubMed] [Google Scholar]
  24. Sawaki Y., Huppert M., Bailey J. W., Yagi Y. Patterns of human antibody reactions in coccidioidomycosis. J Bacteriol. 1966 Jan;91(1):422–427. doi: 10.1128/jb.91.1.422-427.1966. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Spurr A. R. A low-viscosity epoxy resin embedding medium for electron microscopy. J Ultrastruct Res. 1969 Jan;26(1):31–43. doi: 10.1016/s0022-5320(69)90033-1. [DOI] [PubMed] [Google Scholar]
  26. 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]
  27. Wheat R. W., Woodruff W. W., 3rd, Haltiwanger R. S. Occurrence of antigenic (species-specific?) partially 3-O-methylated heteromannans in cell wall and soluble cellular (nonwall) components of Coccidioides immitis mycelia. Infect Immun. 1983 Aug;41(2):728–734. doi: 10.1128/iai.41.2.728-734.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Yturraspe D. J. Clinical evaluation of a latex particle agglutination test and a gel diffusion precipitin test in the diagnosis of canine coccidioidomycosis. J Am Vet Med Assoc. 1971 Apr 1;158(7):1249–1256. [PubMed] [Google Scholar]
  29. Zimmer B. L., Pappagianis D. Characterization of a soluble protein of Coccidiodes immitis with activity as an immunodiffusion-complement fixation antigen. J Clin Microbiol. 1988 Nov;26(11):2250–2256. doi: 10.1128/jcm.26.11.2250-2256.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Zimmer B. L., Pappagianis D. Immunoaffinity isolation and partial characterization of the Coccidioides immitis antigen detected by the tube precipitin and immunodiffusion-tube precipitin tests. J Clin Microbiol. 1989 Aug;27(8):1759–1766. doi: 10.1128/jcm.27.8.1759-1766.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Infection and Immunity are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES