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Diabetes 52:2287-2295, 2003
© 2003 by the American Diabetes Association, Inc.

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

Mia Westerholm-Ormio1, Outi Vaarala2,3, Päivi Pihkala2, Jorma Ilonen4, and Erkki Savilahti1

1 Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland
2 Department of Molecular Medicine, National Public Health Institute, Helsinki, Finland
3 Division of Pediatrics, Department of Molecular and Clinical Medicine, Faculty of Health Sciences, University of Linköping, Linköping, Sweden
4 Department of Virology, University of Turku, Finland

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-1{alpha}- 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, {gamma}-interferon (IFN-{gamma}), and tumor necrosis factor {alpha}-positive cells, the density of IFN-{gamma} mRNA positive cells, and the amounts of IFN-{gamma} 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.

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


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