Endocrine Pathology

, Volume 21, Issue 2, pp 108–114 | Cite as

Anti-Saccharomyces cerevisiae Antibodies are Frequent in Type 1 Diabetes

  • Wahiba Sakly
  • Amani Mankaï
  • Nabil Sakly
  • Yosra Thabet
  • Achouak Achour
  • Leila Ghedira-Besbes
  • Moncef Jeddi
  • Ibtissem Ghedira


Anti-Saccharomyces cerevisiae antibodies (ASCA) have been described in many autoimmune diseases in which there is an increased intestinal permeability. Also in type 1 diabetes (T1D), there is an increased intestinal permeability. Since no data are available about ASCA in T1D, we evaluated, retrospectively, the frequency of ASCA in this disease. ASCA, IgG, and IgA, were determined by ELISA in sera of 224 T1D patients in which coeliac disease has been excluded and 157 healthy control group. The frequency of ASCA (IgG or IgA) was significantly higher in T1D patients than in the control group (24.5% vs. 2.5%, p < 10−7). The same observation was found in children and in adult patients when we compare them to healthy children and blood donors group respectively. Compared to children, adult patients with T1D showed significantly higher frequencies of ASCA of any isotype (38% vs. 13.7%, p < 10−4), both ASCA IgG and IgA (12% vs. 1.6%, p = 0.002), ASCA IgG (35% vs. 9.8%, p < 10−5) and ASCA IgA (15% vs. 5.6%, p = 0.001). The frequency of ASCA was statistically higher in females of all T1D than in males (30.8% vs.17.7%, p = 0.03), in girls than in boys (22% vs.6.2%, p = 0.017), and significantly higher in men than in boys (35.7% vs. 6.2%, p < 10−4). The frequency of ASCA IgG was significantly higher than that of ASCA IgA in all T1D patients (21% vs. 9.8%, p < 0.002), in all females (26.5% vs. 10.2%, p < 0.002), in women (37.9% vs. 12%, p < 0.001). The frequency of ASCA was significantly higher in all long-term T1D than in an inaugural T1D (29% vs. 14.5%, p = 0.019). The same observation was found in adults (45.8% vs. 17.8%, p = 0.01). In long-term T1D patients, ASCA were significantly more frequent in adults than children (45.8% vs. 14.5%, p < 10−4). The frequency of ASCA IgG was significantly higher in long-term T1D than in an inaugural T1D (25.2% vs. 11.6%, p = 0.03). Patients with T1D had a high frequency of ASCA.


Anti-Saccharomyces cerevisiae antibodies Type 1 diabetes Adults Children Tunisia 



anti-Saccharomyces cerevisiae antibodies


type 1 diabetes


coeliac disease



This study is supported by Unité de recherche, Auto-immunité et Allergie (03/UR/07-02), Faculté de Pharmacie de Monastir, Tunisia.


  1. 1.
    Knip M, Siljander H. Autoimmune mechanisms in type 1 diabetes. Autoimmun Rev 7:550-7, 2008.CrossRefPubMedGoogle Scholar
  2. 2.
    Knip M, Veijola R, Virtanen SM, Hyöty H, Vaarala O, Akerblom HK. Environmental triggers and determinants of type 1 diabetes. Diabetes 54(Suppl 2):125-36, 2005.Google Scholar
  3. 3.
    Mokrowiecka A, Daniel P, Słomka M, Majak P, Malecka-Panas E. Clinical utility of serological markers in inflammatory bowel disease. Hepatogastroenterology 56:162-6, 2009.PubMedGoogle Scholar
  4. 4.
    Ashorn S, Välineva T, Kaukinen K, Ashorn M, Braun J, Raukola H, et al. Serological responses to microbial antigens in celiac disease patients during a gluten-free diet. J Clin Immunol 29:190-5, 2009.CrossRefPubMedGoogle Scholar
  5. 5.
    Toumi D, Mankaï A, Belhadj R, Ghedira-Besbes L, Jeddi M, Ghedira I. Anti-Saccharomyces cerevisiae antibodies in coeliac disease. Scand J Gastroenterol 42:821-6, 2007.CrossRefPubMedGoogle Scholar
  6. 6.
    Mallant-Hent RCH, Mary B, von Blomberg E, Yuksel Z, Wahab PJ, Gundy C, et al. Disappearance of anti-Saccharomyces cerevisiae antibodies in coeliac disease during a gluten-free diet. Eur J Gastroenterol Hepatol 18:75-8, 2006.CrossRefPubMedGoogle Scholar
  7. 7.
    Fagoonee S, De Luca L, De Angelis C, Castelli A, Rizzetto M, Pellicano R. Anti-Saccharomyces cerevisiae as unusual antibodies in autoimmune hepatitis. Minerva Gastroenterol Dietol 55:37-40, 2009.PubMedGoogle Scholar
  8. 8.
    Sakly W, Jeddi M, Ghedira I. Anti-Saccharomyces cerevisiae antibodies in primary biliary cirrhosis. Dig Dis Sci 53:1983-7, 2008.CrossRefPubMedGoogle Scholar
  9. 9.
    Krause I, Monselise Y, Milo G, Weinberger A. Anti-Saccharomyces cerevisiae antibodies a novel serologic marker for Behcet’s disease. Clin Exp Rheumatol 20(4 Suppl 26):S21-4, 2002.PubMedGoogle Scholar
  10. 10.
    Aydin SZ, Atagunduz P, Temel M, Bicakcigil M, Tasan D, Direskeneli H. Anti-Saccharomyces cerevisiae antibodies (ASCA) in spondyloarthropathies: a reassessment. Rheumatology (Oxford) 47:142-4, 2008.Google Scholar
  11. 11.
    Dai H, Li Z, Zhang Y, Lv P, Gao XM. Elevated levels of serum antibodies against Saccharomyces cerevisiae mannan in patients with systemic lupus erythematosus. Lupus 18:1087-90, 2009.CrossRefPubMedGoogle Scholar
  12. 12.
    D’Inca R, Annese V, di Leo V, Latiano A, Quaino V, Abazia C, et al. Increased intestinal permeability and NOD2 variants in familial and sporadic Crohn’s disease. Aliment Pharmacol Ther 23:1455-61, 2006.CrossRefPubMedGoogle Scholar
  13. 13.
    Duerksen DR, Wilhelm-Boyles C, Veitch R, Kryszak D, Parry DM. A comparison of antibody testing, permeability testing, and zonulin levels with small-bowel biopsy in celiac disease patients on a gluten-free diet. Dig Dis Sci 55:1026-31, 2009.Google Scholar
  14. 14.
    Feld JJ, Meddings J, Heathcote EJ. Abnormal intestinal permeability in primary biliary cirrhosis. Dig Dis Sci 51:1607-13, 2006.CrossRefPubMedGoogle Scholar
  15. 15.
    Fresko I, Hamuryudan V, Demir M, Hizli N, Sayman H, Melikoglu M, et al. Intestinal permeability in Behcet’s syndrome. Ann Rheum Dis 60:65-6, 2001.CrossRefPubMedGoogle Scholar
  16. 16.
    Vaile JH, Meddings JB, Yacyshyn BR, Russell AS, Maksymowych WP. Bowel permeability and CD45RO expression on circulating CD20+ B cells in patients with ankylosing spondylitis and their relatives. J Rheumatol 26:128-35, 1999.PubMedGoogle Scholar
  17. 17.
    Visser J, Rozing J, Sapone A, Lammers K, Fasano A. Tight junctions, intestinal permeability, and autoimmunity: celiac disease and type 1 diabetes paradigms. Ann N Y Acad Sci 1165:195-205, 2009.CrossRefPubMedGoogle Scholar
  18. 18.
    Bosi E, Molteni L, Radaelli MG, Folini L, Fermo I, Bazzigaluppi E, et al. Increased intestinal permeability precedes clinical onset of type 1 diabetes. Diabetologia 49:2824-7, 2006.CrossRefPubMedGoogle Scholar
  19. 19.
    The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus: Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 20:1183-97, 1997.Google Scholar
  20. 20.
    Mankaï A, Ben Hamouda H, Amri F, Ghedira-Besbes L, Harbi A, Tahar Sfar M, et al. Screening by anti-endomysium antibodies for celiac disease in Tunisian children with type 1 diabetes mellitus. Gastroenterol Clin Biol 31:462-466, 2007PubMedCrossRefGoogle Scholar
  21. 21.
    Mankaï A, Sakly W, Landolsi H, Gueddah L, Sriha B, Ayadi A, et al. Tissue transglutaminase antibodies in celiac disease, comparison of an enzyme linked immunosorbent assay and a dot blot assay. Pathol Biol 53:204-9, 2005.CrossRefPubMedGoogle Scholar
  22. 22.
    Fasano A, Not T, Wang W. Zonulin, a newly discovered modulator of intestinal permeability, and its expression in celiac disease. Lancet 355:1518-9, 2000.CrossRefPubMedGoogle Scholar
  23. 23.
    Franzese A, Lombardi F, Valerio G, Spagnuolo MI. Update on coeliac disease and type 1 diabetes mellitus in childhood. J Pediatr Endocrinol Metab 20:1257-64, 2007.PubMedGoogle Scholar
  24. 24.
    Sapone A, de Magistris L, Pietzak M, Clemente MG, Tripathi A, Cucca F, et al. Zonulin upregulation is associated with increased gut permeability in subjects with type 1 diabetes and their relatives. Diabetes 55:1443-9, 2006.CrossRefPubMedGoogle Scholar
  25. 25.
    Kuitunen M, Saukkonen T, Ilonen J, Akerblom HK, Savilahti E. Intestinal permeability to mannitol and lactulose in children with type 1 diabetes with the HLA-DQB1*02 allele. Autoimmunity 35:365-58, 2002.CrossRefPubMedGoogle Scholar
  26. 26.
    Pozzilli P, Mesturino CA, Crino A, Gross TM, Jeng LM, Visalli N; IMDIAB Group. Is the process of beta-cell destruction in type 1 diabetes at time of diagnosis more extensive in females than in males? Eur J Endocrinol 145:757-61, 2001.CrossRefPubMedGoogle Scholar
  27. 27.
    Westerholm-Ormio M, Vaarala O, Pihkala P, Ilonen J, Savilahti E. Immunologic activity in the small intestinal mucosa of pediatric patients with type 1 diabetes. Diabetes 52:2287-95, 2003.CrossRefPubMedGoogle Scholar
  28. 28.
    Auricchio R, Paparo F, Maglio M, Franzese A, Lombardi F, Valerio G, et al. In vitro-deranged intestinal immune response to gliadin in type 1 diabetes. Diabetes 53:1680-3, 2004.CrossRefPubMedGoogle Scholar
  29. 29.
    Frisk G, Hansson T, Dahlbom I, Tuvemo T. A unifying hypothesis on the development of type 1 diabetes and celiac disease: Gluten consumption may be a shared causative factor. Med Hypotheses 70:1207-9, 2008.CrossRefPubMedGoogle Scholar
  30. 30.
    Vaarala O, Atkinson MA, Neu J. The "perfect storm" for type 1 diabetes: the complex interplay between intestinal microbiota, gut permeability, and mucosal immunity. Diabetes 57:2555-62, 2008.CrossRefPubMedGoogle Scholar
  31. 31.
    Mankaï A, Landolsi H, Chahed A, Gueddah L, Limem M, Ben Abdessalem M, et al. Celiac disease in Tunisia: serological screening in healthy blood donors. Pathol Biol 54:10-3, 2006.CrossRefPubMedGoogle Scholar
  32. 32.
    Smyth DJ, Plagnol V, Walker NM, Cooper JD, Downes K, Yang JH, et al. Shared and distinct genetic variants in type 1 diabetes and celiac disease. N Engl J Med 359:2767-77, 2008.CrossRefPubMedGoogle Scholar
  33. 33.
    Turley SJ, Lee JW, Dutton-Swain N, Mathis D, Benoist C. Endocrine self and gut non-self intersect in the pancreatic lymph nodes. Proc Natl Acad Sci USA 102:17729-33, 2005.CrossRefPubMedGoogle Scholar
  34. 34.
    Pastore MR, Bazzigaluppi E, Belloni C, Arcovio C, Bonifacio E, Bosi E. Six months of gluten-free diet do not influence autoantibody titers, but improve insulin secretion in subjects at high risk for type 1 diabetes. J Clin Endocrinol Metab 88:162-5, 2003.CrossRefPubMedGoogle Scholar
  35. 35.
    Standaert-Vitse A, Jouault T, Vandewalle P, Mille C, Seddik M, Sendid B, et al. Candida albicans is an immunogen for anti-Saccharomyces cerevisiae antibody markers of Crohn’s disease. Gastroenterology130:1764-75, 2006.Google Scholar
  36. 36.
    Willis AM, Coulter WA, Hayes JR, Bell P, Lamey PJ. Factors affecting the adhesion of Candida albicans to epithelial cells of insulin-using diabetes mellitus patients. J Med Microbiol 49:291-3, 2000.PubMedGoogle Scholar
  37. 37.
    Sano H, Terasaki J, Tsutsumi C, Imagawa A, Hanafusa T. A case of fulminant type 1 diabetes mellitus after influenza B infection. Diabetes Res Clin Pract 79:8-9, 2008.CrossRefGoogle Scholar
  38. 38.
    Chiou CC, Chung WH, Hung SI, Yang LC, Hong HS. Fulminant type 1 diabetes mellitus caused by drug hypersensitivity syndrome with human herpesvirus 6 infection. J Am Acad Dermatol 54:S14-7, 2006.CrossRefPubMedGoogle Scholar
  39. 39.
    Dotta F, Censini S, van Halteren AG, Marselli L, Masini M, Dionisi S, et al. Coxsackie B4 virus infection of beta cells and natural killer cell insulitis in recent-onset type 1 diabetic patients. Proc Natl Acad Sci USA 104:5115-20, 2007.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Wahiba Sakly
    • 1
  • Amani Mankaï
    • 1
  • Nabil Sakly
    • 1
  • Yosra Thabet
    • 1
  • Achouak Achour
    • 1
  • Leila Ghedira-Besbes
    • 1
  • Moncef Jeddi
    • 1
  • Ibtissem Ghedira
    • 1
    • 2
  1. 1.Research unit (03UR/07-02)Faculty of PharmacyMonastirTunisia
  2. 2.Laboratory of ImmunologyFarhat Hached HospitalSousseTunisia

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