Skip to main content
PMC home page
Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1995 Mar;99(3):425–432. doi: 10.1111/j.1365-2249.1995.tb05568.x

Antibodies to the Cryptococcus neoformans capsular glucuronoxylomannan are ubiquitous in serum from HIV+ and HIV- individuals.

M Deshaw 1, L A Pirofski 1
PMCID: PMC1534191  PMID: 7882565

Abstract

Murine MoAbs to the Cryptococcus neoformans capsular glucuronoxylomannan (GXM) polysaccharide are protective in mice in vivo and in vitro. The prevalence of protective anti-GXM antibodies in human serum is unknown. To provide further insight into the human antibody response to C. neoformans we determined the prevalence, isotype, and IgG subclass utilization of human anti-GXM antibodies in HIV+ and HIV- sera by a sensitive antigen capture FLISA assay. One hundred and twenty-three sera from the Bronx Municipal Hospital Centre serum bank were studied retrospectively. Seventy were from HIV+ individuals, 10 with a history of cryptococcal meningitis (CM), and 53 were from HIV- individuals. Serum GXM determinations were also performed on 61 HIV+ sera. Our results demonstrated that anti-GXM IgG, IgA, and IgM are ubiquitous in both HIV+ (including those with CM), and HIV- sera. Anti-GXM IgA titres and total serum IgA concentration were elevated in HIV+ sera. Anti-GXM IgG antibodies were almost exclusively isotype-restricted to the IgG2 subclass. Our data also demonstrated elevations of anti-bovine serum albumin (BSA) titres in HIV+ sera. Taken together, our findings confirm hypergammaglobulinaemia and expansion of anti-protein (BSA) antibodies in HIV+ individuals and isotype restriction of human anti-carbohydrate (GXM) antibodies to the IgG2 subclass. Our report of ubiquitous anti-GXM antibodies of the IgG and IgA isotypes suggests that anti-GXM antibodies exist before HIV infection.

Full text

PDF
425

Selected References

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

  1. ALLEN P. Z., KABAT E. A. Persistence of circulating antibodies in human subjects immunized with dextran, levan and blood group substances. J Immunol. 1958 Jun;80(6):495–500. [PubMed] [Google Scholar]
  2. Atkinson M. A., Bowman M. A., Kao K. J., Campbell L., Dush P. J., Shah S. C., Simell O., Maclaren N. K. Lack of immune responsiveness to bovine serum albumin in insulin-dependent diabetes. N Engl J Med. 1993 Dec 16;329(25):1853–1858. doi: 10.1056/NEJM199312163292505. [DOI] [PubMed] [Google Scholar]
  3. Aucouturier P., Couderc L. J., Gouet D., Danon F., Gombert J., Matheron S., Saimot A. G., Clauvel J. P., Preud'homme J. L. Serum immunoglobulin G subclass dysbalances in the lymphadenopathy syndrome and acquired immune deficiency syndrome. Clin Exp Immunol. 1986 Jan;63(1):234–240. [PMC free article] [PubMed] [Google Scholar]
  4. Bardana E. J., Jr, McClatchy J. K., Farr R. S., Minden P. Universal occurrence of antibodies to tubercle bacilli in sera from non-tuberculous and tuberculous individuals. Clin Exp Immunol. 1973 Jan;13(1):65–77. [PMC free article] [PubMed] [Google Scholar]
  5. Bhattacharjee A. K., Bennett J. E., Glaudemans C. P. Capsular polysaccharides of Cryptococcus neoformans. Rev Infect Dis. 1984 Sep-Oct;6(5):619–624. doi: 10.1093/clinids/6.5.619. [DOI] [PubMed] [Google Scholar]
  6. Bindschadler D. D., Bennett J. E. Serology of human cryptococcosis. Ann Intern Med. 1968 Jul;69(1):45–52. doi: 10.7326/0003-4819-69-1-45. [DOI] [PubMed] [Google Scholar]
  7. Briles D. E., Forman C., Hudak S., Claflin J. L. Anti-phosphorylcholine antibodies of the T15 idiotype are optimally protective against Streptococcus pneumoniae. J Exp Med. 1982 Oct 1;156(4):1177–1185. doi: 10.1084/jem.156.4.1177. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Casadevall A., DeShaw M., Fan M., Dromer F., Kozel T. R., Pirofski L. A. Molecular and idiotypic analysis of antibodies to Cryptococcus neoformans glucuronoxylomannan. Infect Immun. 1994 Sep;62(9):3864–3872. doi: 10.1128/iai.62.9.3864-3872.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Casadevall A., Mukherjee J., Devi S. J., Schneerson R., Robbins J. B., Scharff M. D. Antibodies elicited by a Cryptococcus neoformans-tetanus toxoid conjugate vaccine have the same specificity as those elicited in infection. J Infect Dis. 1992 Jun;165(6):1086–1093. doi: 10.1093/infdis/165.6.1086. [DOI] [PubMed] [Google Scholar]
  10. Casadevall A., Mukherjee J., Scharff M. D. Monoclonal antibody based ELISAs for cryptococcal polysaccharide. J Immunol Methods. 1992 Sep 18;154(1):27–35. doi: 10.1016/0022-1759(92)90209-c. [DOI] [PubMed] [Google Scholar]
  11. Currie B. P., Casadevall A. Estimation of the prevalence of cryptococcal infection among patients infected with the human immunodeficiency virus in New York City. Clin Infect Dis. 1994 Dec;19(6):1029–1033. doi: 10.1093/clinids/19.6.1029. [DOI] [PubMed] [Google Scholar]
  12. Diamond R. D., Bennett J. E. Prognostic factors in cryptococcal meningitis. A study in 111 cases. Ann Intern Med. 1974 Feb;80(2):176–181. doi: 10.7326/0003-4819-80-2-176. [DOI] [PubMed] [Google Scholar]
  13. Dromer F., Aucouturier P., Clauvel J. P., Saimot G., Yeni P. Cryptococcus neoformans antibody levels in patients with AIDS. Scand J Infect Dis. 1988;20(3):283–285. doi: 10.3109/00365548809032452. [DOI] [PubMed] [Google Scholar]
  14. Dromer F., Charreire J., Contrepois A., Carbon C., Yeni P. Protection of mice against experimental cryptococcosis by anti-Cryptococcus neoformans monoclonal antibody. Infect Immun. 1987 Mar;55(3):749–752. doi: 10.1128/iai.55.3.749-752.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Dromer F., Salamero J., Contrepois A., Carbon C., Yeni P. Production, characterization, and antibody specificity of a mouse monoclonal antibody reactive with Cryptococcus neoformans capsular polysaccharide. Infect Immun. 1987 Mar;55(3):742–748. doi: 10.1128/iai.55.3.742-748.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Galili U., Mandrell R. E., Hamadeh R. M., Shohet S. B., Griffiss J. M. Interaction between human natural anti-alpha-galactosyl immunoglobulin G and bacteria of the human flora. Infect Immun. 1988 Jul;56(7):1730–1737. doi: 10.1128/iai.56.7.1730-1737.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Gupta S., Ellis M., Cesario T., Ruhling M., Vayuvegula B. Disseminated cryptococcal infection in a patient with hypogammaglobulinemia and normal T cell functions. Am J Med. 1987 Jan;82(1):129–131. doi: 10.1016/0002-9343(87)90388-3. [DOI] [PubMed] [Google Scholar]
  18. HEIDELBERGER M., DILAPI M. M., SIEGEL M., WALTER A. W. Persistence of antibodies in human subjects injected with pneumococcal polysaccharides. J Immunol. 1950 Nov;65(5):535–541. [PubMed] [Google Scholar]
  19. Henderson D. K., Bennett J. E., Huber M. A. Long-lasting, specific immunologic unresponsiveness associated with cryptococcal meningitis. J Clin Invest. 1982 May;69(5):1185–1190. doi: 10.1172/JCI110555. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Huang K. L., Ruben F. L., Rinaldo C. R., Jr, Kingsley L., Lyter D. W., Ho M. Antibody responses after influenza and pneumococcal immunization in HIV-infected homosexual men. JAMA. 1987 Apr 17;257(15):2047–2050. [PubMed] [Google Scholar]
  21. Janoff E. N., Douglas J. M., Jr, Gabriel M., Blaser M. J., Davidson A. J., Cohn D. L., Judson F. N. Class-specific antibody response to pneumococcal capsular polysaccharides in men infected with human immunodeficiency virus type 1. J Infect Dis. 1988 Nov;158(5):983–990. doi: 10.1093/infdis/158.5.983. [DOI] [PubMed] [Google Scholar]
  22. Keller R. G., Pfrommer G. S., Kozel T. R. Occurrences, specificities, and functions of ubiquitous antibodies in human serum that are reactive with the Cryptococcus neoformans cell wall. Infect Immun. 1994 Jan;62(1):215–220. doi: 10.1128/iai.62.1.215-220.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Kozel T. R., Gotschlich E. C. The capsule of cryptococcus neoformans passively inhibits phagocytosis of the yeast by macrophages. J Immunol. 1982 Oct;129(4):1675–1680. [PubMed] [Google Scholar]
  24. Kozel T. R., McGaw T. G. Opsonization of Cryptococcus neoformans by human immunoglobulin G: role of immunoglobulin G in phagocytosis by macrophages. Infect Immun. 1979 Jul;25(1):255–261. doi: 10.1128/iai.25.1.255-261.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Lane H. C., Masur H., Edgar L. C., Whalen G., Rook A. H., Fauci A. S. Abnormalities of B-cell activation and immunoregulation in patients with the acquired immunodeficiency syndrome. N Engl J Med. 1983 Aug 25;309(8):453–458. doi: 10.1056/NEJM198308253090803. [DOI] [PubMed] [Google Scholar]
  26. Levitz S. M. Macrophage-Cryptococcus interactions. Immunol Ser. 1994;60:533–543. [PubMed] [Google Scholar]
  27. Matsuda S., Oka S., Honda M., Takebe Y., Takemori T. Characteristics of IgA antibodies against HIV-1 in sera and saliva from HIV-seropositive individuals in different clinical stages. Scand J Immunol. 1993 Nov;38(5):428–434. doi: 10.1111/j.1365-3083.1993.tb02584.x. [DOI] [PubMed] [Google Scholar]
  28. Melcher G. P., Rinaldi M. G., Frey C. L., Drutz D. J. Demonstration, by immunoelectronmicroscopy, of a cell wall antigen in Trichosporon beigelii that cross-reacts with Cryptococcus neoformans capsular polysaccharide. J Infect Dis. 1988 Oct;158(4):901–902. doi: 10.1093/infdis/158.4.901. [DOI] [PubMed] [Google Scholar]
  29. Miyagawa T., Ochi T., Takahashi H. Hypersensitivity pneumonitis with antibodies to Cryptococcus neoformans. Clin Allergy. 1978 Sep;8(5):501–509. doi: 10.1111/j.1365-2222.1978.tb01503.x. [DOI] [PubMed] [Google Scholar]
  30. Mukherjee J., Casadevall A., Scharff M. D. Molecular characterization of the humoral responses to Cryptococcus neoformans infection and glucuronoxylomannan-tetanus toxoid conjugate immunization. J Exp Med. 1993 Apr 1;177(4):1105–1116. doi: 10.1084/jem.177.4.1105. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Mukherjee J., Pirofski L. A., Scharff M. D., Casadevall A. Antibody-mediated protection in mice with lethal intracerebral Cryptococcus neoformans infection. Proc Natl Acad Sci U S A. 1993 Apr 15;90(8):3636–3640. doi: 10.1073/pnas.90.8.3636. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Mukherjee J., Scharff M. D., Casadevall A. Protective murine monoclonal antibodies to Cryptococcus neoformans. Infect Immun. 1992 Nov;60(11):4534–4541. doi: 10.1128/iai.60.11.4534-4541.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Mukherjee J., Zuckier L. S., Scharff M. D., Casadevall A. Therapeutic efficacy of monoclonal antibodies to Cryptococcus neoformans glucuronoxylomannan alone and in combination with amphotericin B. Antimicrob Agents Chemother. 1994 Mar;38(3):580–587. doi: 10.1128/aac.38.3.580. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Mukherjee S., Lee S., Mukherjee J., Scharff M. D., Casadevall A. Monoclonal antibodies to Cryptococcus neoformans capsular polysaccharide modify the course of intravenous infection in mice. Infect Immun. 1994 Mar;62(3):1079–1088. doi: 10.1128/iai.62.3.1079-1088.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Perlmutter R. M., Hansburg D., Briles D. E., Nicolotti R. A., Davie J. M. Subclass restriction of murine anti-carbohydrate antibodies. J Immunol. 1978 Aug;121(2):566–572. [PubMed] [Google Scholar]
  36. Reason D. C., Lucas A. H. Content and dynamics of the human antibody variable region repertoire to the Haemophilus influenzae type b polysaccharide. Springer Semin Immunopathol. 1993;15(2-3):119–137. doi: 10.1007/BF00201096. [DOI] [PubMed] [Google Scholar]
  37. Rodriguez-Barradas M. C., Musher D. M., Lahart C., Lacke C., Groover J., Watson D., Baughn R., Cate T., Crofoot G. Antibody to capsular polysaccharides of Streptococcus pneumoniae after vaccination of human immunodeficiency virus-infected subjects with 23-valent pneumococcal vaccine. J Infect Dis. 1992 Mar;165(3):553–556. doi: 10.1093/infdis/165.3.553. [DOI] [PubMed] [Google Scholar]
  38. Schlageter A. M., Kozel T. R. Opsonization of Cryptococcus neoformans by a family of isotype-switch variant antibodies specific for the capsular polysaccharide. Infect Immun. 1990 Jun;58(6):1914–1918. doi: 10.1128/iai.58.6.1914-1918.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Schlesinger L. S., Horwitz M. A. A role for natural antibody in the pathogenesis of leprosy: antibody in nonimmune serum mediates C3 fixation to the Mycobacterium leprae surface and hence phagocytosis by human mononuclear phagocytes. Infect Immun. 1994 Jan;62(1):280–289. doi: 10.1128/iai.62.1.280-289.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Scott D. W., Gershon R. K. Determination of total and merecaptothanol-resistant antibody in the same serum sample. Clin Exp Immunol. 1970 Feb;6(2):313–316. [PMC free article] [PubMed] [Google Scholar]
  41. Shirai A., Cosentino M., Leitman-Klinman S. F., Klinman D. M. Human immunodeficiency virus infection induces both polyclonal and virus-specific B cell activation. J Clin Invest. 1992 Feb;89(2):561–566. doi: 10.1172/JCI115621. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Siber G. R., Schur P. H., Aisenberg A. C., Weitzman S. A., Schiffman G. Correlation between serum IgG-2 concentrations and the antibody response to bacterial polysaccharide antigens. N Engl J Med. 1980 Jul 24;303(4):178–182. doi: 10.1056/NEJM198007243030402. [DOI] [PubMed] [Google Scholar]
  43. Steinhoff M. C., Auerbach B. S., Nelson K. E., Vlahov D., Becker R. L., Graham N. M., Schwartz D. H., Lucas A. H., Chaisson R. E. Antibody responses to Haemophilus influenzae type B vaccines in men with human immunodeficiency virus infection. N Engl J Med. 1991 Dec 26;325(26):1837–1842. doi: 10.1056/NEJM199112263252603. [DOI] [PubMed] [Google Scholar]
  44. Sundstrom J. B., Cherniak R. T-cell-dependent and T-cell-independent mechanisms of tolerance to glucuronoxylomannan of Cryptococcus neoformans serotype A. Infect Immun. 1993 Apr;61(4):1340–1345. doi: 10.1128/iai.61.4.1340-1345.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Tabone M. D., Leverger G., Landman J., Aznar C., Boccon-Gibod L., Lasfargues G. Disseminated lymphonodular cryptococcosis in a child with X-linked hyper-IgM immunodeficiency. Pediatr Infect Dis J. 1994 Jan;13(1):77–79. doi: 10.1097/00006454-199401000-00020. [DOI] [PubMed] [Google Scholar]
  46. Yoshida K., Ando M., Sakata T., Araki S. Environmental mycological studies on the causative agent of summer-type hypersensitivity pneumonitis. J Allergy Clin Immunol. 1988 Feb;81(2):475–483. doi: 10.1016/0091-6749(88)90920-7. [DOI] [PubMed] [Google Scholar]
  47. Zuger A., Louie E., Holzman R. S., Simberkoff M. S., Rahal J. J. Cryptococcal disease in patients with the acquired immunodeficiency syndrome. Diagnostic features and outcome of treatment. Ann Intern Med. 1986 Feb;104(2):234–240. doi: 10.7326/0003-4819-104-2-234. [DOI] [PubMed] [Google Scholar]

Articles from Clinical and Experimental Immunology are provided here courtesy of British Society for Immunology

RESOURCES