Background/Aims: Type 1 diabetes (T1DM) is associated with gastric autoimmunity, which is characterized by the presence of parietal cell antibodies (APCA). We investigated gastric autoimmunity prevalence in T1DM children, its manifestations, determinants and association with thyroid gland (anti-Tg, anti-TPO) and pancreatic β-cell autoimmunity (anti-GAD) at baseline and 4 years later. Methods: The initial cohort (D1) included 97 children with T1DM. At follow-up after 4 years (D2), 84.5% of participants were evaluated. We assessed APCA, anti-Tg, anti-TPO, and anti-GAD presence, as well as symptoms of gastritis. APCA-positive patients were evaluated with gastrin, B12, ferritin levels and were submitted to gastroscopy. Results: Thyroid antibody positivity was increased among the APCA-positive patients. Four years later, among initially APCA-positive patients, 2/6 became APCA negative, while 4/6 developed high titers of APCA. On gastroscopy, 2 patients had chronic hypertrophic gastritis and one Helicobacter pylori gastritis. Conclusions: Gastric autoimmunity was associated with thyroid autoimmunity and anti-GAD persistence. After 4 years, the majority of APCA-positive patients developed high titers of APCA and mild symptoms of gastritis. Thus, patients with T1DM, and in particular those with thyroid and/or pancreatic autoimmunity, should have periodic autoantibody screening for the early diagnosis and follow-up of gastric autoimmunity.

Keywords:
Type 1 diabetes, Glutamic acid decarboxylase antibodies, Parietal cell and thyroid autoantibodies, Thyrogastric autoimmunity
1.
Borg H, Fernlund P, Sundkvist G: Protein tyrosine phosphatase-like protein IA2-antibodies plus glutamic acid decarboxylase 65 antibodies (GADA) indicates autoimmunity as frequently as islet cell antibodies assay in children with recently diagnosed diabetes mellitus. Clin Chem 1997;43:2358–2363.
2.
Landin-Olsson M, Palmer JP, Lernmark Å, Blom L, Sundkvist G, Nyström L, Dahlquist G: Predictive value of islet cell and insulin autoantibodies for type 1 (insulin-dependent) diabetes mellitus in a population-based study of newly-diagnosed diabetic and matched control children. Diabetologia 1992;35:1068–1073.
3.
DeBlock CE, De Leeuw IH, Peleckmans PA, Callens D, Maday E, Van Gaal LF: Delayed gastric emptying and gastric autoimmunity in type 1 diabetes. Diabetes Care 2002;25:912–917.
4.
De Block CE, De Leeuw IH, Vertommen JJ, Rooman RP, Du Caju MV, Van Campenhout CM, Weyler JJ, Winnock F, Van Autreve J, Gorus FK, Belgian Diabetes Registry: Beta-cell, thyroid, gastric, adrenal and coeliac autoimmunity and HLA-DQ types in type 1 diabetes. Clin Exp Immunol 2001;126:236–241.
5.
Frohlich-Reiterer EE, Huber J, Katz H, Suppan E, Obermayer-Pietsch B, Deutschmann A, et al: Do children and adolescents with type 1 diabetes mellitus have a higher frequency of parietal cell antibodies than healthy controls? J Pediatr Gastroenterol Nutr 2011;52:558–562.
6.
De Block CE, De Leeuw IH, Rooman RP, Winnock F, Du Caju MV, Van Gaal LF: Gastric parietal cell antibodies are associated with glutamic acid decarboxylase-65 antibodies and the HLA DQA1*0501-DQB1*0301 haplotype in type 1 diabetes mellitus. Belgian Diabetes Registry. Diabet Med 2000;17:618–622.
7.
De Block CE, De Leeuw IH, Van Gaal LF, and the Belgian Diabetes Registry: High prevalence of manifestations of gastric autoimmunity in parietal cell antibody-positive type 1 diabetic patients. J Clin Endocrinol Metab 1999;84:4062–4067.
8.
Kordonouri O, Klinghammer A, Lang EB, Gruters-Keslich A, Grabert M, Holl RW: Thyroid autoimmunity in children and adolescents with type 1 diabetes. Diabetes Care 2002;24:1346–1350.
9.
Maugender D, Guilhem I, Karacatsanis C, Poirier JY, Leguerrier AM, Lorcy Y, Derrien C, Sonnet E, Massart C: Anti-TPO antibodies and screening of thyroid dysfunction in type 1 diabetic patients. Ann Endocrinol (Paris) 2000;61:524–530.
10.
Kordonouri O, Deiss D, Danne T, Dorow A, Bassir C, Gruters-Kieslich A: Predictivity of thyroid autoantibodies for the development of thyroid disorders in children and adolescents with type 1 diabetes. Diabet Med 2002;19: 518–521.
11.
Alberti KG; Zimmet PZ: Definition, diagnosis and classification of diabetes mellitus and its complications. 1. Diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet Med 1998;15:539–553.
12.
Karavanaki K, Kakleas K, Paschali E, Kefalas N, Konstantopoulos I, Hadjiathanasiou C, Kanariou M, Karayianni C: Screening for associated autoimmunity in children and adolescents with type 1 diabetes mellitus. Horm Res 2009;71:201–206.
13.
Kakleas K, Paschali E, Kefalas N, Fotinou A, Kanariou M, Karayianni Ch, Karavanaki K: Factors for thyroid autoimmunity in children and adolescents with type 1 diabetes mellitus. Ups J Med Sci 2009;114:214–220.
14.
Landin-Olsson M, Karlsson A, Dahlquist G, Blom L, Lernmark A, Sundkvist G: Islet cell and other organ-specific autoantibodies in all children developing type 1 (insulin dependent) diabetes mellitus in Sweden during one year and in matched control children. Diabetologia 1989;2:387–395.
15.
Jaeger C, Hatziagelaki E, Petzoldt R, Bretzel RG: Comparative analysis of organ-specific autoantibodies and celiac disease-associated antibodies in type 1 diabetic patients, their first-degree relatives, and healthy control subjects. Diabetes Care 2001;24:27–32.
16.
Jacobson DL, Gange SJ, Rose NR, Graham NM: Epidemiology and estimated population burden of selected autoimmune diseases in the United States. Clin Immunol Immunopathol 1997;84:223–243.
17.
Neufeld M, Maclaren N, Blizzard R: Autoimmune polyglandular syndromes. Pediatr Ann 1980;9:154–163.
18.
Barova H, Perusicova J, Hill M, Sterzl I, Vondra K, Masek Z: Anti-GAD-positive patients with type 1 diabetes mellitus have higher prevalence of autoimmune thyroiditis than anti-GAD negative patients with type1 and type 2 diabetes mellitus. Physiol Res 2004;53:279–286.
19.
Talal N: Autoimmunity and the immunological network. Athritis Rheum 1978;21:853.
20.
Decochez K, Tits J, Coolens JL, et al: High frequency of persisting or increasing islet-specific autoantibody levels after diagnosis of type 1 diabetes presenting before 40 years of age. Diabetes Care 2000;23:838–844.
21.
Becker KGRM, Simon JE, Bailey-Wilson B, Freidlin WE, Biddison HF, McFarland JM: Clustering of non-major histocompatibility complex susceptibility candidate loci in human autoimmune diseases. Proc Natl Acad Sci USA 1998;95:9979–9984.
22.
Becker KG: Comparative genetics of type 1 diabetes and autoimmune disease: common loci, common pathways? Diabetes 1999;48:1353–1358.
23.
Silveira PA, Baxter AG, Cain WE, van Driel IR: A major linkage region on distal chromosome 4 confers susceptibility to mouse autoimmune gastritis. J Immunol 1999;162:5106–5111.
24.
Tsai LH, Taniyama K, Tanaka C: Gamma-aminobutyric acid stimulates acid secretion from the isolated guinea pig stomach. Am J Physiol 1987;253:G601–G606.
25.
Ahren B: GABA inhibits thyroid hormone secretion in the mouse. Thyroidology 1989;1:105–108.
26.
Esteban M, Baxter AG: Polyspecificity of autoimmune responses in type 1 (autoimmune) diabetes. Clin Exp Immunol 2001;126:184–186.
27.
De Block CEM, De Leeuw IH, Van Gaal LF: Autoimmune gastritis in type 1 diabetes: a clinically oriented review. J Clin Endocrinol Metab 2008;93:363–371.
28.
Hershko C, Ronson A, Souroujon M, Maschler I, Heyd J, Patz J: Variable hematologic presentation of autoimmune gastritis: age-related progression from iron deficiency to cobalamin depletion. Blood 2006;107:1673–1679.
29.
Muhsen K, Barak M, Henig C, Alpert G, Ornoy A, Cohen D: Is the association between Helicobacter pylori infection and anemia age dependent? Helicobacter 2010;15:467–472.
30.
Gürbüz AK, Küçükkardali Y, Yazgan Y, Ozel M, Polat T: Does eradication of Helicobacter pylori infection reduce hypergastrinema during long term therapy with proton pump inhibitors? Turk J Gastroenterol 2002;13:159–163.
31.
Segni M, Borrelli O, Pucarelli I, Delle Fave G, Pasquino AM, Annibale B: Early manifestations of gastric autoimmunity in patients with juvenile autoimmune thyroid disease. J Clin Endocrinol Metab 2004;89:4944–4948.
© 2012 S. Karger AG, Basel
2012
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