Immunologic Activity in the Small Intestinal Mucosa of Pediatric Patients With Type 1 Diabetes

  1. Mia Westerholm-Ormio1,
  2. Outi Vaarala23,
  3. Päivi Pihkala2,
  4. Jorma Ilonen4 and
  5. Erkki Savilahti1
  1. 1Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland
  2. 2Department of Molecular Medicine, National Public Health Institute, Helsinki, Finland
  3. 3Division of Pediatrics, Department of Molecular and Clinical Medicine, Faculty of Health Sciences, University of Linköping, Linköping, Sweden
  4. 4Department of Virology, University of Turku, Finland
  1. Address correspondence and reprint requests to Mia Westerholm-Ormio, Hospital for Children and Adolescents, Research Laboratory, Biomedicum Helsinki, B433b, P.O. Box 63, FIN-00014 University of Helsinki, Finland. E-mail address: mia.westerholm-ormio{at}hus.fi

Abstract

Involvement of gut immune system has been implicated in the pathogenesis of type 1 diabetes. However, few studies have been performed on the gut mucosa from patients with type 1 diabetes. Thus, we characterized the stage of immune activation in jejunal biopsy samples from 31 children with type 1 diabetes by immunohistochemistry, in situ hybridization, and RT-PCR. We found enhanced expressions of HLA-DR, HLA-DP, and intercellular adhesion molecule-1 by immunohistochemistry even on structurally normal intestine of patients with type 1 diabetes and no signs of celiac disease. In addition, the densities of IL-1α- and IL-4-positive cells detected by immunohistochemistry and IL-4 mRNA-expressing cells evaluated by in situ hybridization were increased in the lamina propria in patients with type 1 diabetes and normal mucosa. Instead, the densities of IL-2, γ-interferon (IFN-γ), and tumor necrosis factor α-positive cells, the density of IFN-γ mRNA positive cells, and the amounts of IFN-γ mRNA detected by RT-PCR correlated with the degree of celiac disease in patients with type 1 diabetes. Our study supports the hypothesis that a link exists between the gut immune system and type 1 diabetes.

Footnotes

    • Accepted May 22, 2003.
    • Received October 31, 2002.
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