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. 1996 Mar;3(2):219–226. doi: 10.1128/cdli.3.2.219-226.1996

Specific antibody response to oligomannosidic epitopes in Crohn's disease.

B Sendid 1, J F Colombel 1, P M Jacquinot 1, C Faille 1, J Fruit 1, A Cortot 1, D Lucidarme 1, D Camus 1, D Poulain 1
PMCID: PMC170283  PMID: 8991640

Abstract

Elevated antibody levels against the yeast Saccharomyces cerevisiae have been reported in sera from patients with Crohn's disease and not with ulcerative colitis. The aim of the study was to identify the nature of the epitopes supporting this antibody response. Whole cells from different S. cerevisiae strains were selected in immunofluorescence assay for their ability to differentiate the antibody responses of patients with Crohn's disease and ulcerative colitis. Their cell wall phosphopeptidomannans were then tested as antigen in enzyme-linked immunosorbent assay (ELISA) against sera from 42 patients with Crohn's disease, 20 patients with ulcerative colitis, and 34 healthy controls. Graded chemical degradations were performed on the most reactive strain phosphopeptidomannan. The discriminating epitope was determined through gas-liquid chromatography-mass spectrometry. The greatest discrimination among patients with Crohn's disease, ulcerative colitis, and controls was obtained with Su1, a S. cerevisiae strain used in brewing of beer. ELISA directed against phosphopeptidomannan of this strain was 64% sensitive and 77% specific for discriminating Crohn's disease versus ulcerative colitis and 71% sensitive and 89% specific for Crohn's disease versus controls. Periodate oxidation and selective degradation demonstrated that the most important polysaccharide epitope was shared by both the acid-stable and the alkali-labile domains of the phosphopeptidomannan. The determination of oligomannose sequences of S. cerevisiae Su1 phosphopeptidomannans suggested that a mannotetraose, Man (1 --> 3)Man(1 --> 2)Man(1 --> 2)Man, supported the serological response seen in Crohn's disease. Further identification of the immunogen eliciting this antibody response as a marker of the disease may help to understand its etiology.

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Selected References

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  1. Barclay G. R., McKenzie H., Pennington J., Parratt D., Pennington C. R. The effect of dietary yeast on the activity of stable chronic Crohn's disease. Scand J Gastroenterol. 1992;27(3):196–200. doi: 10.3109/00365529208999948. [DOI] [PubMed] [Google Scholar]
  2. Barnes R. M., Allan S., Taylor-Robinson C. H., Finn R., Johnson P. M. Serum antibodies reactive with Saccharomyces cerevisiae in inflammatory bowel disease: is IgA antibody a marker for Crohn's disease? Int Arch Allergy Appl Immunol. 1990;92(1):9–15. doi: 10.1159/000235217. [DOI] [PubMed] [Google Scholar]
  3. Best W. R., Becktel J. M., Singleton J. W., Kern F., Jr Development of a Crohn's disease activity index. National Cooperative Crohn's Disease Study. Gastroenterology. 1976 Mar;70(3):439–444. [PubMed] [Google Scholar]
  4. Byron J. K., Clemons K. V., McCusker J. H., Davis R. W., Stevens D. A. Pathogenicity of Saccharomyces cerevisiae in complement factor five-deficient mice. Infect Immun. 1995 Feb;63(2):478–485. doi: 10.1128/iai.63.2.478-485.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Faille C., Mackenzie D. W., Michalski J. C., Poulain D. Evaluation of an enzyme immunoassay using neoglycolipids constructed from Candida albicans oligomannosides to define the specificity of anti-mannan antibodies. Eur J Clin Microbiol Infect Dis. 1992 May;11(5):438–446. doi: 10.1007/BF01961859. [DOI] [PubMed] [Google Scholar]
  6. Fournet B., Strecker G., Leroy Y., Montreuil J. Gas--liquid chromatography and mass spectrometry of methylated and acetylated methyl glycosides. Application to the structural analysis of glycoprotein glycans. Anal Biochem. 1981 Sep 15;116(2):489–502. doi: 10.1016/0003-2697(81)90393-6. [DOI] [PubMed] [Google Scholar]
  7. Frosch M., Görgen I., Boulnois G. J., Timmis K. N., Bitter-Suermann D. NZB mouse system for production of monoclonal antibodies to weak bacterial antigens: isolation of an IgG antibody to the polysaccharide capsules of Escherichia coli K1 and group B meningococci. Proc Natl Acad Sci U S A. 1985 Feb;82(4):1194–1198. doi: 10.1073/pnas.82.4.1194. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Fukazawa Y. Antigenic structure of Candida albicans. Immunochemical basis of the serologic specificity of the mannans in yeasts. Immunol Ser. 1989;47:37–62. [PubMed] [Google Scholar]
  9. Giaffer M. H., Clark A., Holdsworth C. D. Antibodies to Saccharomyces cerevisiae in patients with Crohn's disease and their possible pathogenic importance. Gut. 1992 Aug;33(8):1071–1075. doi: 10.1136/gut.33.8.1071. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hamada T., Noda F., Hayashi K. Structure of Cell Wall and Extracellular Mannans from Saccharomyces rouxii and Their Relationship to a High Concentration of NaCl in the Growth Medium. Appl Environ Microbiol. 1984 Oct;48(4):708–712. doi: 10.1128/aem.48.4.708-712.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hayette M. P., Strecker G., Faille C., Dive D., Camus D., Mackenzie D. W., Poulain D. Presence of human antibodies reacting with Candida albicans O-linked oligomannosides revealed by using an enzyme-linked immunosorbent assay and neoglycolipids. J Clin Microbiol. 1992 Feb;30(2):411–417. doi: 10.1128/jcm.30.2.411-417.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hearn V. M., Wilson E. V., Latgé J. P., Mackenzie D. W. Immunochemical studies of Aspergillus fumigatus mycelial antigens by polyacrylamide gel electrophoresis and western blotting techniques. J Gen Microbiol. 1990 Aug;136(8):1525–1535. doi: 10.1099/00221287-136-8-1525. [DOI] [PubMed] [Google Scholar]
  13. Heelan B. T., Allan S., Barnes R. M. Identification of a 200-kDa glycoprotein antigen of Saccharomyces cerevisiae. Immunol Lett. 1991 Jun;28(3):181–185. doi: 10.1016/0165-2478(91)90001-q. [DOI] [PubMed] [Google Scholar]
  14. Hollander D., Vadheim C. M., Brettholz E., Petersen G. M., Delahunty T., Rotter J. I. Increased intestinal permeability in patients with Crohn's disease and their relatives. A possible etiologic factor. Ann Intern Med. 1986 Dec;105(6):883–885. doi: 10.7326/0003-4819-105-6-883. [DOI] [PubMed] [Google Scholar]
  15. Kikuchi S., Ohinata A., Tsumuraya Y., Hashimoto Y., Kaneko Y., Matsushima H. Production and characterization of antibodies to the beta-(1-->6)-galactotetraosyl group and their interaction with arabinogalactan-proteins. Planta. 1993;190(4):525–535. doi: 10.1007/BF00224792. [DOI] [PubMed] [Google Scholar]
  16. Kocourek J., Ballou C. E. Method for fingerprinting yeast cell wall mannans. J Bacteriol. 1969 Dec;100(3):1175–1181. doi: 10.1128/jb.100.3.1175-1181.1969. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Lindberg E., Magnusson K. E., Tysk C., Järnerot G. Antibody (IgG, IgA, and IgM) to baker's yeast (Saccharomyces cerevisiae), yeast mannan, gliadin, ovalbumin and betalactoglobulin in monozygotic twins with inflammatory bowel disease. Gut. 1992 Jul;33(7):909–913. doi: 10.1136/gut.33.7.909. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Maekawa S., Ohara T. On the existence of cross-reactive antigens between Candida and Mycobacterium. Jpn J Microbiol. 1966 Apr;10(1):1–11. doi: 10.1111/j.1348-0421.1966.tb00286.x. [DOI] [PubMed] [Google Scholar]
  19. Main J., McKenzie H., Yeaman G. R., Kerr M. A., Robson D., Pennington C. R., Parratt D. Antibody to Saccharomyces cerevisiae (bakers' yeast) in Crohn's disease. BMJ. 1988 Oct 29;297(6656):1105–1106. doi: 10.1136/bmj.297.6656.1105. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Manning-Zweerink M., Maloney C. S., Mitchell T. G., Weston H. Immunoblot analyses of Candida albicans-associated antigens and antibodies in human sera. J Clin Microbiol. 1986 Jan;23(1):46–52. doi: 10.1128/jcm.23.1.46-52.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Markwell M. A., Haas S. M., Bieber L. L., Tolbert N. E. A modification of the Lowry procedure to simplify protein determination in membrane and lipoprotein samples. Anal Biochem. 1978 Jun 15;87(1):206–210. doi: 10.1016/0003-2697(78)90586-9. [DOI] [PubMed] [Google Scholar]
  22. May G. R., Sutherland L. R., Meddings J. B. Is small intestinal permeability really increased in relatives of patients with Crohn's disease? Gastroenterology. 1993 Jun;104(6):1627–1632. doi: 10.1016/0016-5085(93)90638-s. [DOI] [PubMed] [Google Scholar]
  23. McKenzie H., Main J., Pennington C. R., Parratt D. Antibody to selected strains of Saccharomyces cerevisiae (baker's and brewer's yeast) and Candida albicans in Crohn's disease. Gut. 1990 May;31(5):536–538. doi: 10.1136/gut.31.5.536. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. McKenzie H., Parratt D., Main J., Pennington C. R. Antigenic heterogeneity of strains of Saccharomyces cerevisiae and Candida albicans recognised by serum antibodies from patients with Crohn's disease. FEMS Microbiol Immunol. 1992 Apr;4(4):219–224. doi: 10.1111/j.1574-6968.1992.tb04997.x. [DOI] [PubMed] [Google Scholar]
  25. Müller W. E., Bachmann M., Weiler B. E., Schröder H. C., Uhlenbruck G., Shinoda T., Shimizu H., Ushijima H. Antibodies against defined carbohydrate structures of Candida albicans protect H9 cells against infection with human immunodeficiency virus-1 in vitro. J Acquir Immune Defic Syndr. 1991;4(7):694–703. [PubMed] [Google Scholar]
  26. Nakajima T., Ballou C. E. Structure of the linkage region between the polysaccharide and protein parts of Saccharomyces cerevisiae mannan. J Biol Chem. 1974 Dec 10;249(23):7685–7694. [PubMed] [Google Scholar]
  27. Nishikawa A., Sekine T., Ikeda R., Shinoda T., Fukazawa Y. Reassessment of antigenic determinant of Saccharomyces cerevisiae serotype Ia. Microbiol Immunol. 1990;34(10):825–840. doi: 10.1111/j.1348-0421.1990.tb01061.x. [DOI] [PubMed] [Google Scholar]
  28. Nnalue N. A., Weintraub A., Lindberg A. A. Properties of a rat monoclonal antibody reactive with both the mannan of Candida species and the O-antigen 6,7 polysaccharide of serogroup C1 salmonellae. Infect Immun. 1991 Jan;59(1):229–233. doi: 10.1128/iai.59.1.229-233.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Odds F. C., Evans E. G. Distribution of pathogenic yeasts and humoral antibodies to candida among hospital inpatients. J Clin Pathol. 1980 Aug;33(8):750–756. doi: 10.1136/jcp.33.8.750. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Okawa Y., Takahata T., Kawamata M., Miyauchi M., Shibata N., Suzuki A., Kobayashi H., Suzuki S. Temperature-dependent change of serological specificity of Candida albicans NIH A-207 cells cultured in yeast extract-added Sabouraud liquid medium: disappearance of surface antigenic factors 4, 5, and 6 at high temperature. FEBS Lett. 1994 May 30;345(2-3):167–171. doi: 10.1016/0014-5793(94)00434-x. [DOI] [PubMed] [Google Scholar]
  31. Poulain D., Faille C., Delaunoy C., Jacquinot P. M., Trinel P. A., Camus D. Probable presence of beta(1-2)-linked oligomannosides that act as human immunoglobulin G3 epitopes and are distributed over a Candida albicans 14- to 18-kilodalton antigen. Infect Immun. 1993 Mar;61(3):1164–1166. doi: 10.1128/iai.61.3.1164-1166.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Puzo G. The carbohydrate- and lipid-containing cell wall of mycobacteria, phenolic glycolipids: structure and immunological properties. Crit Rev Microbiol. 1990;17(4):305–327. doi: 10.3109/10408419009105730. [DOI] [PubMed] [Google Scholar]
  33. Ryan C. A. Oligosaccharide signals: from plant defense to parasite offense. Proc Natl Acad Sci U S A. 1994 Jan 4;91(1):1–2. doi: 10.1073/pnas.91.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Shibata N., Ichikawa T., Tojo M., Takahashi M., Ito N., Okubo Y., Suzuki S. Immunochemical study on the mannans of Candida albicans NIH A-207, NIH B-792, and J-1012 strains prepared by fractional precipitation with cetyltrimethylammonium bromide. Arch Biochem Biophys. 1985 Dec;243(2):338–348. doi: 10.1016/0003-9861(85)90511-9. [DOI] [PubMed] [Google Scholar]
  35. Stainsby K. J., Lowes J. R., Allan R. N., Ibbotson J. P. Antibodies to Mycobacterium paratuberculosis and nine species of environmental mycobacteria in Crohn's disease and control subjects. Gut. 1993 Mar;34(3):371–374. doi: 10.1136/gut.34.3.371. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Trinel P. A., Borg-von-Zepelin M., Lepage G., Jouault T., Mackenzie D., Poulain D. Isolation and preliminary characterization of the 14- to 18-kilodalton Candida albicans antigen as a phospholipomannan containing beta-1,2-linked oligomannosides. Infect Immun. 1993 Oct;61(10):4398–4405. doi: 10.1128/iai.61.10.4398-4405.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Trinel P. A., Faille C., Jacquinot P. M., Cailliez J. C., Poulain D. Mapping of Candida albicans oligomannosidic epitopes by using monoclonal antibodies. Infect Immun. 1992 Sep;60(9):3845–3851. doi: 10.1128/iai.60.9.3845-3851.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Ukabam S. O., Clamp J. R., Cooper B. T. Abnormal small intestinal permeability to sugars in patients with Crohn's disease of the terminal ileum and colon. Digestion. 1983;27(2):70–74. doi: 10.1159/000198932. [DOI] [PubMed] [Google Scholar]
  39. Wayne L. G., Hollander D., Anderson B., Sramek H. A., Vadheim C. M., Rotter J. I. Immunoglobulin A (IgA) and IgG serum antibodies to mycobacterial antigens in Crohn's disease patients and their relatives. J Clin Microbiol. 1992 Aug;30(8):2013–2018. doi: 10.1128/jcm.30.8.2013-2018.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Woodward M. P., Young W. W., Jr, Bloodgood R. A. Detection of monoclonal antibodies specific for carbohydrate epitopes using periodate oxidation. J Immunol Methods. 1985 Apr 8;78(1):143–153. doi: 10.1016/0022-1759(85)90337-0. [DOI] [PubMed] [Google Scholar]
  41. Yacyshyn B. R., Meddings J. B. CD45RO expression on circulating CD19+ B cells in Crohn's disease correlates with intestinal permeability. Gastroenterology. 1995 Jan;108(1):132–137. doi: 10.1016/0016-5085(95)90017-9. [DOI] [PubMed] [Google Scholar]
  42. Young C. A., Sonnenberg A., Burns E. A. Lymphocyte proliferation response to baker's yeast in Crohn's disease. Digestion. 1994;55(1):40–43. doi: 10.1159/000201121. [DOI] [PubMed] [Google Scholar]

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