Advertisement

Clinical Reviews in Allergy & Immunology

, Volume 45, Issue 2, pp 152–161 | Cite as

Anti-Saccharomyces cerevisiae Autoantibodies in Autoimmune Diseases: from Bread Baking to Autoimmunity

  • Maurizio Rinaldi
  • Roberto Perricone
  • Miri Blank
  • Carlo Perricone
  • Yehuda ShoenfeldEmail author
Article

Abstract

Saccharomyces cerevisiae is best known as the baker’s and brewer’s yeast, but its residual traces are also frequent excipients in some vaccines. Although anti-S. cerevisiae autoantibodies (ASCAs) are considered specific for Crohn’s disease, a growing number of studies have detected high levels of ASCAs in patients affected with autoimmune diseases as compared with healthy controls, including antiphospholipid syndrome, systemic lupus erythematosus, type 1 diabetes mellitus, and rheumatoid arthritis. Commensal microorganisms such as Saccharomyces are required for nutrition, proper development of Peyer’s aggregated lymphoid tissue, and tissue healing. However, even the commensal nonclassically pathogenic microbiota can trigger autoimmunity when fine regulation of immune tolerance does not work properly. For our purposes, the protein database of the National Center for Biotechnology Information (NCBI) was consulted, comparing Saccharomyces mannan to several molecules with a pathogenetic role in autoimmune diseases. Thanks to the NCBI bioinformation technology tool, several overlaps in molecular structures (50–100 %) were identified when yeast mannan, and the most common autoantigens were compared. The autoantigen U2 snRNP B″ was found to conserve a superfamily protein domain that shares 83 % of the S. cerevisiae mannan sequence. Furthermore, ASCAs may be present years before the diagnosis of some associated autoimmune diseases as they were retrospectively found in the preserved blood samples of soldiers who became affected by Crohn’s disease years later. Our results strongly suggest that ASCAs’ role in clinical practice should be better addressed in order to evaluate their predictive or prognostic relevance.

Keywords

Anti-Saccharomyces cerevisiae autoantibodies Autoimmune diseases Molecular mimicry Autoantigenicity Vaccines 

References

  1. 1.
    Sicard D, Legras JL (2011) Bread, beer and wine: yeast domestication in the Saccharomyces sensu stricto complex. C R Biol 334(3):229–236PubMedCrossRefGoogle Scholar
  2. 2.
    Krause I, Blank M, Cervera R, Font J, Matthias T, Pfeiffer S, Wies I, Fraser A, Shoenfeld Y (2007) Cross-reactive epitopes on β2-glycoprotein-I and Saccharomyces cerevisiae in patients with the antiphospholipid syndrome. Ann N Y Acad Sci 1108:481–488PubMedCrossRefGoogle Scholar
  3. 3.
    Israeli E, Grotto I, Gilburd B, Balicer RD, Goldin E, Wiik A, Shoenfeld Y (2005) Anti-Saccharomyces cerevisiae and antineutrophil cytoplasmic antibodies as predictors of inflammatory bowel disease. Gut 54(9):1232–1236PubMedCrossRefGoogle Scholar
  4. 4.
    Dai H, Li Z, Zhang Y, Lv P, Gao XM (2009) Elevated levels of serum antibodies against Saccharomyces cerevisiae mannan in patients with systemic lupus erythematosus. Lupus 18(12):1087–1090PubMedCrossRefGoogle Scholar
  5. 5.
    Sakly W, Mankaï A, Sakly N, Thabet Y, Achour A, Ghedira-Besbes L, Jeddi M, Ghedira I (2010) Anti-Saccharomyces cerevisiae antibodies are frequent in type 1 diabetes. Endocr Pathol 21(2):108–114PubMedCrossRefGoogle Scholar
  6. 6.
    Dai H, Li Z, Zhang Y, Lv P, Gao XM (2009) Elevated levels of serum IgA against Saccharomyces cerevisiae mannan in patients with rheumatoid arthritis. Cell Mol Immunol 6(5):361–366PubMedCrossRefGoogle Scholar
  7. 7.
    Agmon-Levin N, Lian Z, Shoenfeld Y (2011) Explosion of autoimmune diseases and the mosaic of old and novel factors. Cell Moll Immunol 8(3):189–192CrossRefGoogle Scholar
  8. 8.
    Shoenfeld Y, Gilburd B, Abu-Shakra M, Amital H, Barzilai O, Berkun Y, Blank M, Zandman-Goddard G, Katz U, Krause I, Langevitz P, Levy Y, Orbach H, Pordeus V, Ram M, Sherer Y, Toubi E, Tomer Y (2008) The mosaic of autoimmunity: genetic factors involved in autoimmune diseases. Isr Med Assoc J 10(1):3–7PubMedGoogle Scholar
  9. 9.
    Shoenfeld Y, Zandman-Goddard G, Stojanovich L, Cutolo M, Amital H, Levy Y, Abu-Shakra M, Barzilai O, Berkun Y, Blank M, de Carvalho JF, Doria A, Gilburd B, Katz U, Krause I, Langevitz P, Orbach H, Pordeus V, Ram M, Toubi E, Sherer Y (2008) The mosaic of autoimmunity: hormonal and environmental factors involved in autoimmune diseases—2008. Isr Med Assoc J 10:8–12PubMedGoogle Scholar
  10. 10.
    Shoenfeld Y, Blank M, Abu-Shakra M, Amital H, Barzilai O, Berkun Y, Bizzaro N, Gilburd B, Zandman-Goddard G, Katz U, Krause I, Langevitz P, Mackay IR, Orbach H, Ram M, Sherer Y, Toubi E, Gershwin ME (2008) The mosaic of autoimmunity: prediction, autoantibodies and therapy in autoimmune diseases—2008. Isr Med Assoc J 10(1):13–19PubMedGoogle Scholar
  11. 11.
    Proal AD, Albert PJ, Marshall T (2009) Autoimmune disease in the era of the metagenome. Autoimmun Rev 8:677–681PubMedCrossRefGoogle Scholar
  12. 12.
    Kivity S, Agmon-Levin N, Blank M, Shoenfeld Y (2009) Infections and autoimmunity—friends or foes? Trends Immunol 30:409–414PubMedCrossRefGoogle Scholar
  13. 13.
    Guilherme L, Kalil J, Cunningham M (2006) Molecular mimicry in the autoimmune pathogenesis of rheumatic heart disease. Autoimmunity 39(1):31–39PubMedCrossRefGoogle Scholar
  14. 14.
    Duke RC (1989) Self recognition by T cells. I. Bystander killing of target cells bearing syngeneic MHC antigens. J Exp Med 1(170):59–71CrossRefGoogle Scholar
  15. 15.
    Agmon-Levin N, Ram M, Barzilai O, Porat-Katz BS, Parikman R, Selmi C, Gershwin ME, Anaya JM, Youinou P, Bizzaro N, Tincani A, Tzioufas AG, Cervera R, Stojanovich L, Martin J, Gonzalez-Gay MA, Valentini G, Blank M, SanMarco M, Rozman B, Bombardieri S, De Vita S, Shoenfeld Y (2009) Prevalence of hepatitis C serum antibody in autoimmune diseases. J Autoimmun 32:261–266PubMedCrossRefGoogle Scholar
  16. 16.
    Nahum A, Dadi H, Bates A, Roifman CM (2012) The biological significance of TLR3 variant, L412F, in conferring susceptibility to cutaneous candidiasis, CMV and autoimmunity. Autoimmun Rev 11:341–347PubMedCrossRefGoogle Scholar
  17. 17.
    Villamón E, Gozalbo D, Roig P, Murciano C, O’Connor JE, Fradelizi D, Gil ML (2004) Myeloid differentiation factor 88 (MyD88) is required for murine resistance to Candida albicans and is critically involved in Candida-induced production of cytokines. Eur Cytokine Netw 15:263–271PubMedGoogle Scholar
  18. 18.
    Selmi C, Leung PS, Sherr DH, Diaz M, Nyland JF, Monestier M, Rose NR, Gershwin ME (2012) Mechanisms of environmental influence on human autoimmunity: a national institute of environmental health sciences expert panel workshop. J Autoimmun 28Google Scholar
  19. 19.
    Sarra M, Pallone F, Macdonald TT, Monteleone G (2010) IL-23/IL-17 axis in IBD. Inflamm Bowel Dis 16:1808–1813PubMedCrossRefGoogle Scholar
  20. 20.
    Chervonsky AV (2010) Influence of microbial environment on autoimmunity. Nat Immunol 11:28–35PubMedCrossRefGoogle Scholar
  21. 21.
    Fernández S, Molina IJ, Romero P, González R, Peña J, Sánchez F, Reynoso FR, Pérez-Navero JL, Estevez O, Ortega C, Santamaría M (2011) Characterization of gliadin-specific Th17 cells from the mucosa of celiac disease patients. Am J Gastroenterol 106:528–538PubMedCrossRefGoogle Scholar
  22. 22.
    Bruce D, Yu S, Ooi JH, Cantorna MT (2011) Converging pathways lead to overproduction of IL-17 in the absence of vitamin D signaling. Int Immunol 23:519–528PubMedCrossRefGoogle Scholar
  23. 23.
    Iborra M, Bernuzzi F, Invernizzi P, Danese S (2012) MicroRNAs in autoimmunity and inflammatory bowel disease: crucial regulators in immune response. Autoimmun Rev 11:305–314PubMedCrossRefGoogle Scholar
  24. 24.
    O’Connell RM, Taganov KD, Boldin MP, Cheng G, Baltimore D (2007) MicroRNA-155 is induced during the macrophage inflammatory response. Proc Natl Acad Sci U S A 30(104):1604–1609CrossRefGoogle Scholar
  25. 25.
    Monk CE, Hutvagner G, Arthur JS (2010) Regulation of miRNA transcription in macrophages in response to Candida albicans. PLoS One 5:e13669PubMedCrossRefGoogle Scholar
  26. 26.
    Thai TH, Calado DP, Casola S, Ansel KM, Xiao C, Xue Y, Murphy A, Frendewey D, Valenzuela D, Kutok JL, Schmidt-Supprian M, Rajewsky N, Yancopoulos G, Rao A, Rajewsky K (2007) Regulation of the germinal center response by microRNA-155. Science 316:604–608PubMedCrossRefGoogle Scholar
  27. 27.
    Pordeus V, Szyper-Kravitz M, Levy RA, Vaz NM, Shoenfeld Y (2008) Infections and autoimmunity: a panorama. Clin Rev Allergy Immunol 34:283–299PubMedCrossRefGoogle Scholar
  28. 28.
    Levin LI, Munger KL, Rubertone MV, Peck CA, Lennette ET, Spiegelman D, Ascherio A (2005) Temporal relationship between elevation of Epstein–Barr virus antibody titers and initial onset of neurological symptoms in multiple sclerosis. JAMA 293:2496–2500PubMedCrossRefGoogle Scholar
  29. 29.
    Shinohara H, Nagi-Miura N, Ishibashi K, Adachi Y, Ishida-Okawara A, Oharaseki T, Takahashi K, Naoe S, Suzuki K, Ohno N (2006) Beta-mannosyl linkages negatively regulate anaphylaxis and vasculitis in mice, induced by CAWS, fungal PAMPS composed of mannoprotein-beta-glucan complex secreted by Candida albicans. Biol Pharm Bull 29:1854–1861PubMedCrossRefGoogle Scholar
  30. 30.
    Sørensen R, Thiel S, Jensenius JC (2005) Mannan-binding-lectin-associated serine proteases, characteristics and disease associations. Springer Semin Immunopathol 27:299–319PubMedCrossRefGoogle Scholar
  31. 31.
    Standaert-Vitse A, Jouault T, Vandewalle P, Mille C, Seddik M, Sendid B, Mallet JM, Colombel JF, Poulain D (2006) Candida albicans is an immunogen for anti-Saccharomyces cerevisiae antibody markers of Crohn’s disease. Gastroenterology 130:1764–1775PubMedCrossRefGoogle Scholar
  32. 32.
    Lidar M, Langevitz P, Shoenfeld Y (2009) The role of infection in inflammatory bowel disease: initiation, exacerbation and protection. Isr Med Assoc J 11:558–563PubMedGoogle Scholar
  33. 33.
    Luong M, Lam JS, Chen J, Levitz SM (2007) Effects of fungal N- and O-linked mannosylation on the immunogenicity of model vaccines. Vaccine 25(22):4340–4344PubMedCrossRefGoogle Scholar
  34. 34.
    Ardiani A, Higgins JP, Hodge JW (2010) Vaccines based on whole recombinant Saccharomyces cerevisiae cells. FEMS Yeast Res 10(8):1060–1069PubMedCrossRefGoogle Scholar
  35. 35.
    Haller AA, Lauer GM, King TH, Kemmler C, Fiolkoski V, Lu Y, Bellgrau D, Rodell TC, Apelian D, Franzusoff A, Duke RC (2007) Whole recombinant yeast-based immunotherapy induces potent T cell responses targeting HCV NS3 and Core proteins. Vaccine 25:1452–1463PubMedCrossRefGoogle Scholar
  36. 36.
    van de Veerdonk FL, Kullberg BJ, van der Meer JW, Gow NA, Netea MG (2008) Host–microbe interactions: innate pattern recognition of fungal pathogens. Curr Opin Microbiol 11:305–312PubMedCrossRefGoogle Scholar
  37. 37.
    Shoenfeld Y, Agmon-Levin N (2010) “ASIA”—autoimmune/inflammatory syndrome induced by adjuvants. J Autoimmun 36(1):4–8PubMedCrossRefGoogle Scholar
  38. 38.
    Israeli E, Agmon-Levin N, Blank M, Shoenfeld Y (2009) Adjuvants and autoimmunity. Lupus 18(13):1217–1225PubMedCrossRefGoogle Scholar
  39. 39.
    Agmon-Levin N, Paz Z, Israeli E, Shoenfeld Y (2009) Vaccines and autoimmunity. Nat Rev Rheumatol 5(11):648–652PubMedCrossRefGoogle Scholar
  40. 40.
    Offit PA, Jew RK (2003) Addressing parents’ concerns: do vaccines contain harmful preservatives, adjuvants, additives, or residuals? Pediatrics 112(6):1394–1397PubMedCrossRefGoogle Scholar
  41. 41.
    Moore M, Fabricatorian D, Selby W (2002) Assessment and relevance of enzyme-linked immunosorbent assay for antibodies to Saccharomyces cerevisiae in Australian patients with inflammatory bowel disease. Inter Med J 32(7):349–352CrossRefGoogle Scholar
  42. 42.
    Cinemre H, Bilir C, Gokosmanoglu F, Kadakal F (2007) Anti-Saccharomyces cerevisiae antibodies in acute myocardial infarction. J Investig Med 55(8):444–449PubMedCrossRefGoogle Scholar
  43. 43.
    Jager NA, Teteloshvili N, Zeebregts CJ, Westra J, Bijl M (2012) Macrophage folate receptor-β (FR-β) expression in auto-immune inflammatory rheumatic diseases: a forthcoming marker for cardiovascular risk? Autoimmun Rev 11:621–626PubMedCrossRefGoogle Scholar
  44. 44.
    Krause I, Weinberger A (2008) Behçet’s disease. Krause I. Curr Opin Rheumatol 20(1):82–87PubMedCrossRefGoogle Scholar
  45. 45.
    Choi CH, Kim TI, Kim BC, Shin SJ, Lee SK, Kim WH, Kim HS (2006) Anti-Saccharomyces cerevisiae antibody in intestinal Behçet’s disease patients: relation to clinical course. Dis Colon Rectum 49(12):1849–1859PubMedCrossRefGoogle Scholar
  46. 46.
    Rho YH, Chung CP, Oeser A, Solus J, Asanuma Y, Sokka T, Pincus T, Raggi P, Gebretsadik T, Shintani A, Stein CM (2009) Inflammatory mediators and premature coronary atherosclerosis in rheumatoid arthritis. Arthritis Rheum 61(11):1580–1585PubMedCrossRefGoogle Scholar
  47. 47.
    Yazıcı D, Aydın SZ, Yavuz D, Tarçın O, Deyneli O, Direskeneli H, Akalın S (2010) Anti-Saccharomyces Cerevisiae antibodies (ASCA) are elevated in autoimmune thyroid disease ASCA in autoimmune thyroid disease. Endocrine 38(2):194–198PubMedCrossRefGoogle Scholar
  48. 48.
    Barta Z, Zold E, Nagy A, Zeher M, Csipo I (2011) Celiac disease and microscopic colitis: a report of 4 cases. World J Gastroenterol 17(16):2150–2154PubMedCrossRefGoogle Scholar
  49. 49.
    Lidar M, Langevitz P, Barzilai O, Ram M, Porat-Katz BS, Bizzaro N, Tonutti E, Maieron R, Chowers Y, Bar-Meir S, Shoenfeld Y (2009) Infectious serologies and autoantibodies in inflammatory bowel disease: insinuations at a true pathogenic role. Ann N Y Acad Sci 1173:640–648PubMedCrossRefGoogle Scholar
  50. 50.
    Fagoonee S, De Luca L, De Angelis C, Castelli A, Rizzetto M, Pellicano R (2009) Anti-Saccharomyces cerevisiae as unusual antibodies in autoimmune hepatitis. Minerva Gastroenterol Dietol 55:37–40PubMedGoogle Scholar
  51. 51.
    Bueno de Mesquita M, Ferrante M, Henckaerts L, Joossens M, Janssens V, Hlavaty T, Pierik M, Joossens S, Van Schuerbeek N, Van Assche G, Rutgeerts P, Vermeire S, Hoffman I (2009) Clustering of (auto)immune diseases with early-onset and complicated inflammatory bowel disease. Eur J Pediatr 168(5):575–583PubMedCrossRefGoogle Scholar
  52. 52.
    Czaja AJ, Shums Z, Donaldson PT, Norman GL (2004) Frequency and significance of antibodies to Saccharomyces cerevisiae in autoimmune hepatitis. Dig Dis Sci 49(4):611–618PubMedCrossRefGoogle Scholar
  53. 53.
    Muratori P, Muratori L, Guidi M, Maccariello S, Pappas G, Ferrari R, Gionchetti P, Campieri M, Bianchi FB (2003) Anti-Saccharomyces cerevisiae antibodies (ASCA) and autoimmune liver diseases. Clin Exp Immunol 132(3):473–476PubMedCrossRefGoogle Scholar
  54. 54.
    Fassler J, Cooper P (2008) BLAST glossary. 2011 Jul 14. In: BLAST® Help [Internet]. National Center for Biotechnology Information (US), BethesdaGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Maurizio Rinaldi
    • 1
  • Roberto Perricone
    • 1
  • Miri Blank
    • 2
  • Carlo Perricone
    • 3
  • Yehuda Shoenfeld
    • 2
    Email author
  1. 1.Rheumatology, Allergology and Clinical Immunology, Department of Internal MedicineUniversity of Rome Tor VergataRomeItaly
  2. 2.Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Sackler Faculty of MedicineTel Aviv UniversityRamat GanIsrael
  3. 3.Reumatologia, Dipartimento di Medicina Interna e Specialità MedicheSapienza Università di RomaRomeItaly

Personalised recommendations