Immunologic activity in the small intestinal mucosa of pediatric patients with type 1 diabetes.
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.
Westerholm-Ormio
Mia
M
Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland. mia.westerholm-ormio@hus.fi
Vaarala
Outi
O
Pihkala
Päivi
P
Ilonen
Jorma
J
Savilahti
Erkki
E
D000293:Adolescent; D000906:Antibodies; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology* / Q000503:physiopathology*; D005260:Female; D015870:Gene Expression / Q000276:immunology; D005838:Genotype; D006680:HLA Antigens / Q000235:genetics; D000949:Histocompatibility Antigens Class II / Q000032:analysis / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis / Q000276:immunology; D007371:Interferon-gamma / Q000235:genetics; D007375:Interleukin-1 / Q000235:genetics; D007376:Interleukin-2 / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics; D007413:Intestinal Mucosa / Q000276:immunology*; D007583:Jejunum / Q000737:chemistry / Q000276:immunology*; D019394:Ki-67 Antigen / Q000032:analysis; D008297:Male; D010761:Phosphorus Radioisotopes; D012333:RNA, Messenger / Q000032:analysis; D054398:Receptors, CCR4; D019713:Receptors, CCR5 / Q000235:genetics; D019707:Receptors, Chemokine / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D000906:Antibodies; C515354:CCR4 protein, human; D006680:HLA Antigens; D000949:Histocompatibility Antigens Class II; D007375:Interleukin-1; D007376:Interleukin-2; D019394:Ki-67 Antigen; D010761:Phosphorus Radioisotopes; D012333:RNA, Messenger; D054398:Receptors, CCR4; D019713:Receptors, CCR5; D019707:Receptors, Chemokine; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D015847:Interleukin-4; D007371:Interferon-gamma