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

Department of Immunology, University of Tartu, Tartu, Estonia.
Cellular & molecular immunology (Impact Factor: 4.11). 02/2011; 8(2):150-6. DOI: 10.1038/cmi.2010.66
Source: PubMed


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.

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Available from: Marika Mikelsaar, Apr 08, 2014
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    • "Recent studies have demonstrated that patients with type 1 diabetes and newly detected coeliac disease exhibit severely altered intestinal permeability, strong local immune activation, and increased immunoregulatory mechanisms in the small bowel [Uibo et al., 2011]. As suggested by studies by Vaarala [2008], it is possible that infections caused by HEVs are sufficient to increase intestinal permeability. "
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    ABSTRACT: Coeliac disease and type 1 diabetes are autoimmune diseases that may share the same initiating environmental factors. In this study, the occurrence of type 1 diabetes associated autoantibodies (GADA and IA-2A) and tissue transglutaminase autoantibodies (TGA) was determined in patients with confirmed viral infections and no signs of type 1 diabetes or coeliac disease. Serum samples from 82 Cuban patients tested positive for PCR and IgG specific to enterovirus (HEV, serotype echovirus 16, 20 samples), Epstein-Barr virus (EBV, 20 samples), cytomegalovirus (CMV, 21 samples), and hepatitis C virus (HCV, 21 samples); and sera from 164 controls negative serologically to EBV, CMV, HCV, and echovirus 16 were enrolled in the study. All subjects were screened for GADA, IA-2A, and TGA. The prevalence of TGA in patients infected with HEV, EBV, CMV, or HCV was 55% (11/20), 25% (5/20), 9.5% (2/21), and 9.5% (2/21), respectively. GADA and IA-2A were found in 15% (3/20) and 25% (5/20) of patients infected with HEV. None of the patients infected by EBV, CMV, and HCV had GADA or IA-2A. All children infected with HEV who were positive for type 1 diabetes-associated autoantibodies were also TGA-positive. None of the sera from uninfected subjects were positive for GADA, IA-2A or TGA. In conclusion, TGA can develop during infection with HEV, EBV, CMV, or HCV, while the emergence of islet cell related autoantibodies is restricted to HEV infections. The findings suggest that HEV may be a shared environmental factor for the development of islet and gut-related autoimmunity.
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    • "Recently, in samples from the small bowel mucosa from patients with celiac disease and type 1 diabetes a low expression of tight junction protein 1 (TJP1) mRNA has been observed, indicating an increase in intestinal permeability that might represent a causative factor. Furthermore, the highest expression of Forkhead box P3 (FoxP3) mRNA, a marker of regulatory T cells was observed, suggesting an increased immunoregolatory mechanisms (Uibo et al., 2011). The mean prevalence of celiac disease in type 1 diabetes is about 8%, with an extremely variable range (from 1% up to 11%) (Kakleas et al., 2010), almost 10-20 fold higher than observed in general pediatric population (Maki et al., 2003). "

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    03/2011; 5(3):119-121. DOI:10.3923/rjmsci.2011.119.121
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