Celiac disease in patients with type 1 diabetes: a condition with distinct changes in intestinal immunity?

• Published in: Cellular & molecular immunology Vol. 8; no. 2; pp. 150 - 156
• Main Authors: Uibo, Raivo, Panarina, Marina, Teesalu, Kaupo, Talja, Ija, Sepp, Epp, Utt, Meeme, Mikelsaar, Marika, Heilman, Kaire, Uibo, Oivi, Vorobjova, Tamara
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-03-2011; Nature Publishing Group
• Subjects: Adolescent; Animals; Antibodies; Antibodies, Bacterial - immunology; Antigens; Autoantibodies; Bacterial Proteins - immunology; Bifidobacterium - immunology; Biomedical and Life Sciences; Biomedicine; Cattle; Celiac disease; Celiac Disease - complications; Celiac Disease - immunology; Celiac Disease - microbiology; Celiac Disease - pathology; Child; Child, Preschool; Children; Diabetes; Diabetes mellitus (insulin dependent); Diabetes Mellitus, Type 1 - complications; Diabetes Mellitus, Type 1 - immunology; Diabetes Mellitus, Type 1 - microbiology; Diabetes Mellitus, Type 1 - pathology; Environmental factors; Female; Forkhead protein; Forkhead Transcription Factors - genetics; Forkhead Transcription Factors - metabolism; Foxp3 protein; Gene Expression Regulation; Gliadin - immunology; GTP-Binding Proteins - genetics; GTP-Binding Proteins - metabolism; Humans; Immunity; Immunity (Disease); Immunity - immunology; Immunoglobulin A; Immunoglobulin A - immunology; Immunoglobulin G; Immunoglobulin G - immunology; Immunology; Immunoregulation; Infant; Intestinal Mucosa - enzymology; Intestinal Mucosa - pathology; Intestines - immunology; Intestines - pathology; Lactoglobulins - immunology; Lymphocytes T; Male; Medical Microbiology; Membrane Proteins - genetics; Membrane Proteins - metabolism; Microbiology; mRNA; Mucosa; Permeability; Phosphoproteins - genetics; Phosphoproteins - metabolism; research-article; RNA, Messenger - genetics; RNA, Messenger - metabolism; Serum levels; Small intestine; Tight junctions; Transglutaminase 2; Transglutaminases - genetics; Transglutaminases - metabolism; Vaccine; Zonula Occludens-1 Protein; β-Lactoglobulin; celiac disease; immunoregulation; type 1 diabetes; intestinal mucosa; autoimmunity
• ISSN: 1672-7681; 2042-0226
• DOI: 10.1038/cmi.2010.66

Two common chronic childhood diseases—celiac disease (CD) and type 1 diabetes (T1D)—result from complex pathological mechanisms where genetic susceptibility, environmental exposure, alterations in intestinal permeability and immune responses play central roles. In this study, we investigated whether these characteristics were universal for CD independently of T1D association. For this purpose, we studied 36 children with normal small-bowel mucosa and 26 children with active CD, including 12 patients with T1D. In samples from the small-bowel mucosa, we detected the lowest expression of tight junction protein 1 (TJP1) mRNA in CD patients with T1D, indicating an increase in intestinal permeability. Furthermore, these samples displayed the highest expression of forkhead box P3 (FoxP3) mRNA, a marker for regulatory T cells, as compared with other patient groups. At the same time, serum levels of IgA antibodies specific for the CD-related antigens deamidated gliadin and tissue transglutaminase (tTG) were the highest in CD patients with T1D. In contrast, no significant differences were found in IgA or IgG antibodies specific for bovine beta-lactoglobulin or
Bifidobacterium adolescentis
DSM 20083-derived proteins. There were also no differences in the transamidating activity of serum autoantibodies between patients and control individuals. Our results show that patients with T1D and newly detected CD exhibit severely altered intestinal permeability, strong local immune activation and increased immunoregulatory mechanisms in the small bowel. Further study is required to determine whether these extreme changes in this CD subgroup are due to some specific environmental factors (virus infections), unknown genetic effects or autoimmune reactions to antigenic targets in intracellular tight junctions.