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Horm Metab Res 2001; 33(9): 564-567
DOI: 10.1055/s-2001-17215
Original Clinical

© Georg Thieme Verlag Stuttgart · New York

Comparison of the Prevalence of Glutamic Acid Decarboxylase (GAD65) and Gliadin Antibodies (AGA) in a Randomly Selected Adult Estonian Population

R. Uibo 1 , E. P. Sullivan 2 , O. Uibo 3 , A. Lernmark 2 , L. Salur 1 , T. Kivik 4 , M. Mandel 1
  • 1 Department of Immunology, University of Tartu, Estonia
  • 2 Department of Medicine, University of Washington, Seattle, Washington, USA
  • 3 Department of Paediatrics, University of Tartu, Estonia
  • 4 Karksi-Nuia Outpatient Department, Viljandi County, Estonia
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Publication History

Publication Date:
17 September 2001 (online)

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We aimed to test the hypothesis that gluten might be associated with the development of islet cell autoimmunity. A random sample of 200 persons (87 males, mean age 42.4 years) from Estonia including one patient with type I diabetes mellitus was studied. IgG-type glutamic acid decarboxylase (GAD65) antibodies were determined using radioligand-binding assay and IgG/IgA-type gliadin antibodies (AGA) by enzyme-linked immunosorbent assay. Generic HLA-DRB1* alleles were analyzed using a polymerase chain reaction. Although our results revealed the highest GAD65Ab index and a high IgA-type AGA in a person with diabetes, no correlation between GAD65Ab and AGA values was revealed among the other 199 persons (p > 0.05). There were also no differences between test values among persons with and without different HLA-DRB1* alleles (p > 0.05). In the GAD65Ab assay, one person (0.5 %; 95 % CI: 0 - 1.5) out of 199 exceeded the 99th centile of the GAD65Ab index. In summary, the present study does not confirm the possibility that there is a relationship between the immune reactivity against GAD65 and gliadin, at least in persons without type I DM.

Key words:

Autoimmunity - Celiac Disease - Gluten - Islet-Cell Antibodies - HLA-DR - Type I Diabetes Mellitus

References

  • 1 Schranz D B, Lernmark A. Immunology in diabetes: an update.  Diabetes Metab Rev. 1998;  14 3-29
    CrossrefPubMedGoogle Scholar
  • 2 Sanjeevi C B, Falorni A, Kockum I, Hagopian W A, Lernmark A. HLA and glutamic acid decarboxylase in human insulin-dependent diabetes mellitus.  Diabetic Med. 1996;  13 209-217
    CrossrefPubMedGoogle Scholar
  • 3 Leslie R DG, Atkinson M A, Notkins A L. Autoantigens IA-2 and GAD in type I (insulin-dependent) diabetes.  Diabetologia. 1999;  42 3-14
    CrossrefPubMedGoogle Scholar
  • 4 Kasuga A, Maruyama T, Nakamoto S, Ozawa Y, Suzuki Y, Saruta T. High-titer autoantibodies against glutamic acid decarboxylase plus autoantibodies against insulin and IA-2 predicts insulin requirement in adult diabetic patients.  J Autoimm. 1999;  12 131-135
    CrossrefPubMedGoogle Scholar
  • 5 Petersen J S, Kyvik K O, Bingley P J, Gale E A, Green A, Dyrberg T, Beck-Nielsen H. Population based study of prevalence of islet cell autoantibodies in monozygotic and dizygotic Danish twin pairs with insulin dependent diabetes mellitus.  BMJ. 1997;  314 1575-1579
    PubMedGoogle Scholar
  • 6 Redondo M J, Rewers M, Yu L, Garg S, Pilcher C C, Elliot R B, Eisenbarth G S. Genetic determination of islet cell autoimmunity in monozygotic twin, dizygotic twin, and non-twin siblings of patients with type I diabetes: prospective twin study.  BMJ. 1999;  318 698-702
    PubMedGoogle Scholar
  • 7 . DERI Group . Secular trends in incidence of childhood IDDM in 10 countries.  Diabetes. 1990;  39 858-864
    PubMedGoogle Scholar
  • 8 Virtanen S M, Räsänen L, Mäenpää J, Akerblom H K. Dietary survey of Finnish adolescent diabetics and non-diabetic controls.  Acta Paediatr Scand. 1987;  76 801-808
    PubMedGoogle Scholar
  • 9 Bonifacio E, Ziegler A G, Hummel M, Dittler J, Lampasona V, Pastore M R, Bosi E. Gluten: is it also a determinant of islet autoimmunity?.  Diabetes Metab Rev. 1998;  14 258-259
    CrossrefPubMedGoogle Scholar
  • 10 Rossi T M, Tjota A. Serological indicators of celiac disease.  J Pediatr Gastroenterol Nutr. 1998;  26 205-210
    CrossrefPubMedGoogle Scholar
  • 11 Volta U, de Franceschi L, Molinaro N, Tetta C, Bianchi F B. Organ-specific autoantibodies in coeliac disease: do they represent an epiphenomenon or the expression of associated autoimmune disorders.  Ital J Gastroenterol Hepatol. 1997;  29 18-21
    PubMedGoogle Scholar
  • 12 Cronin C C, Shanahan F. Insulin-dependent diabetes mellitus and coeliac disease.  Lancet. 1998;  349 1096-1097
    PubMedGoogle Scholar
  • 13 Kostal M, Michalkova D, Hrabcakova D. Antireticulin antibodies in sera of children with insulin-dependent diabetes mellitus.  Diab Res Clin Pract. 1992;  17 183-190
    CrossrefPubMedGoogle Scholar
  • 14 Shanahan F, McKenna R, McCarthy C F, Drury M I. Coeliac disease and diabetes mellitus: a study of 24 patients with HLA typing.  Quart J Med. 1982;  51 329-335
    PubMedGoogle Scholar
  • 15 Catassi C, Natalini G, Rätsch I M, Gabrielli O, Coppa G V, Giorgi P L. Documented latent coeliac disease in a child with insulin-dependent diabetes mellitus.  Eur J Pediatr. 1991;  150 832-834
    PubMedGoogle Scholar
  • 16 Mäki M, Huupponen T, Holm K, Hällström O. Seroconversion of reticulin autoantibodies predicts coeliac disease in insulin dependent diabetes mellitus.  Gut. 1995;  36 239-242
    PubMedGoogle Scholar
  • 17 Sjöberg K, Eriksson K F, Bredberg A, Wassmuth R, Eriksson S. Screening for coeliac disease in adult insulin-dependent diabetes mellitus.  J Intern Med. 1998;  243 133-140
    CrossrefPubMedGoogle Scholar
  • 18 Falorni A, Ortqvist E, Persson B, Lernmark A. Radioimmunoassays for glutamic acid decarboxylase (GAD65) and GAD65 autoantibodies using 35S and 3H recombinant human ligands.  J Immunol Methods. 1995;  186 89-99
    CrossrefPubMedGoogle Scholar
  • 19 Grubin C F, Daniels T, Toivola B. A novel radioligand binding assay to determine diagnostic accuracy of isoform-specific glutamic acid decarboxylase antibodies in childhood IDDM.  Diabetologia. 1994;  37 344-350
    PubMedGoogle Scholar
  • 20 Mire-Sluis A R, Das R G, Lernmark A. The development of a World Health Organisation international standard for islet cell antibodies: the aims and design of an international collaborative study.  Diabetes Metab Res Rev. 1999;  15 72-77
    CrossrefPubMedGoogle Scholar
  • 21 Uibo O, Uibo R, Kleimola V, Jõgi T, Mäki M. Serum IgA anti-gliadin antibodies in an adult population sample. High prevalence without celiac disease.  Dig Dis Sci. 1993;  38 2034-2037
    CrossrefPubMedGoogle Scholar
  • 22 Uibo O. Childhood coeliac disease in Estonia: occurrence, screening, diagnosis and clinical characterization.  University of Tartu:; Doctoral Thesis, 1994
    Google Scholar
  • 23 Kulmala P, Savola K, Petersen J S, Vähäsalo P, Karjalainen J, Löppönen T, Dyrberg T, Akerblom H K, Knip M. Prediction of insulin-dependent diabetes mellitus in siblings of children with diabetes. A population-based study.  J Clin Invest. 1998;  101 327-336
    PubMedGoogle Scholar
  • 24 Walker-Smith J, Guandalini S, Schmitz J, Shmerling D H, Visakorpi J K. Revised criteria for diagnosis of coeliac disease. Report of working group of European Society for Paediatric Gastroenterology and Nutrition.  Arch Dis Child. 1990;  65 909-911
    CrossrefPubMedGoogle Scholar
  • 25 Savilahti E, Örmälä T, Saukkonen T, Sandini-Phjavuori U, Kantele J M, Arato A, Ilonen J, Akeblom H K. Jejuna of patients with insulin-dependent diabetes mellitus (IDDM) show signs of immune activation.  Clin Exp Immunol. 1999;  116 70-77
    CrossrefPubMedGoogle Scholar
  • 26 Adojaan B, Knip M, Vähäsalo P, Karjalainen J, Kalits I, Akeblom H K. Relationship between the incidence of childhood IDDM and the frequency of ICA positivity in nondiabetic children in general population.  Diabetes Care. 1996;  19 1452-1453
    PubMedGoogle Scholar
  • 27 Rolandsson O, Hägg E, Hampe C, Sullivan E P, Nilsson M, Jansson G, Hallmans G, Lernmark A. Glutamate decarboxylase (GAD65) and tyrosine phosphatase-like protein (IA-2) autoantibodies index in a regional population is related to glucose intolerance antibody mass index.  Diabetologia. 1999;  42 555-559
    CrossrefPubMedGoogle Scholar
  • 28 Niskanen L K, Tuomi T, Karjalainen J, Groop L C, Uusitupa M IJ. GAD antibodies in NIDDM. Ten year follow-up from the diagnosis.  Diabetes Care. 1995;  18 1557-1565
    PubMedGoogle Scholar
  • 29 Ruige J B, Batstra M R, Aanstoot H J, Bouter L M, Bruining G J, De Neeling J N, Heine R J. Low prevalence of antibodies to GAD65 in a 50- to 74-year-old general Dutch population. The Hoorn study.  Diabetes Care. 1997;  20 1108-1110
    PubMedGoogle Scholar
  • 30 Bosi E, Garancini M P, Poggiali F, Bonifacio E, Gallus G. Low prevalence of islet autoimmunity in adult diabetes and low predictive value of islet autoantibodies in the general adult population of northern Italy.  Diabetologia. 1999;  42 840-844
    CrossrefPubMedGoogle Scholar
  • 31 Adojaan B, Podar T. Immune and genetic factors of childhood onset IDDM in Estonia (in Estonian).  Estonian Physician. 1998;  6 488-491
    PubMedGoogle Scholar
  • 32 Nejentsev S, Koskinen S, Sjöroos M, Reijonen H, Schwartz E I, Kovalchuk L, Sochnev A, Adojaan B, Podar T, Knip M, Simell O, Koskenvuo M, Akeblom H K, Ilonen J. Distribution of insulin-dependent diabetes mellitus (IDDM)-related HLA alleles correlates with the difference in IDDM incidence in four populations of the Eastern Baltic region.  Tissue Antigens. 1998;  52 473-477
    PubMedGoogle Scholar
  • 33 Caillat-Zucman S, Djilali-Saiah I, Timsit J, et al. Insulin dependent diabetes mellitus (IDDM): 12th International Histocompatibility Workshop study.  In: Genetic Diversity of HLA. Functional and Medical Implication.  Paris:; EDK Medical and Scientific International Publisher, 1997: 389-398
    Google Scholar

R. Uibo,M.D., D.Sci. 

Department of Immunology
University of Tartu

19 Ravila Street
Tartu 51014
Estonia


Phone: + 372 (7) 374 231

Fax: + 372 (7) 374 232

Email: Raivo.Uibo@ut.ee

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