Immunologic Activity in the Small Intestinal Mucosa of Pediatric Patients With Type 1 Diabetes
- 1Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland
- 2Department of Molecular Medicine, National Public Health Institute, Helsinki, Finland
- 3Division of Pediatrics, Department of Molecular and Clinical Medicine, Faculty of Health Sciences, University of Linköping, Linköping, Sweden
- 4Department of Virology, University of Turku, Finland
- 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.
- AEC, carbatzole
- CCR, chemokine receptor
- CD, celiac disease
- EMA, endomysium antibodies
- ICAM-1, intercellular adhesion molecule-1
- IEL, intraepithelial lymphocyte
- IFN-γ, γ-interferon
- IL, interleukin
- mAb, monoclonal antibody
- TCR, T-cell receptor
- TNF-α, tumor necrosis factor α
- tTGA, tissue transglutaminase antibodies
Footnotes
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- Accepted May 22, 2003.
- Received October 31, 2002.
- DIABETES
