Evidence for the role of a human intestinal adenovirus in the pathogenesis of coeliac disease.

Kagnoff, Martin F.; Paterson, Yvonne; Kumar, Parveen; Kasarda, Donald D.; Carbone, Federico; Unsworth, D J; Austin, Raleigh K.

doi:10.1136/gut.28.8.995

Cited by 213 publications

(104 citation statements)

References 29 publications

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“…It is tempting to speculate that you may need a triggering gastrointestinal infection inducing primary target cell damage and/or a proinflammatory cytokine milieu in the gut epithelium to initiate the disease process subsequently driven by dietary gluten toward clinical celiac disease in genetically predisposed individuals. Previous studies have indicated that adenovirus infections might contribute to the pathogenesis of celiac disease (24,25), but only a few studies have focused on the possible role of microbes in this disease.…”

Section: A Pathogenetic Model Of Type 1 Diabetesmentioning

confidence: 99%

Environmental Triggers and Determinants of Type 1 Diabetes

et al. 2005

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Type 1 diabetes is perceived as a chronic immune-mediated disease with a subclinical prodromal period characterized by selective loss of insulin-producing ␤-cells in the pancreatic islets in genetically susceptible subjects. A series of evidence supports a critical role of exogenous factors in the development of type 1 diabetes, such as 1) the fact that <10% of individuals with HLA-conferred diabetes susceptibility do progress to clinical disease, 2) a pairwise concordance of type 1 diabetes of <40% among monozygotic twins, 3) a more than 10-fold difference in the disease incidence among Caucasians living in Europe, 4) a severalfold increase in the incidence over the last 50 years, and 5) migration studies indicating that the disease incidence has increased in population groups who have moved from a low-incidence to a high-incidence region. This article discusses the trigger-booster hypothesis claiming that the diabetic disease process is triggered by an exogenous factor with definite seasonal variation and driven by one or several other environmental determinants. In addition, there are a series of modifying factors affecting the fate and pace of the process. Accordingly, progression to clinical type 1 diabetes typically requires the unfortunate combination of genetic disease susceptibility, a diabetogenic trigger, and a high exposure to a driving antigen. Diabetes 54 (Suppl. 2):S125-S136, 2005

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Section: A Pathogenetic Model Of Type 1 Diabetesmentioning

confidence: 99%

Environmental Triggers and Determinants of Type 1 Diabetes

et al. 2005

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“…Since Kagnoff et al [31 ]reported in their landmark paper that adenoviruses may be involved in the pathogenesis of CD, researchers have tried to identify the role of infectious disease in its pathogenesis. The parallel findings of a potential role of virus infections in type 1 diabetes, another autoimmune disease that also confers increased risk for CD [32,33,34], has raised this interest.…”

Section: Non-dietary Risk Factors For CDmentioning

confidence: 99%

Timing of Introduction of Gluten and Celiac Disease Risk

Ludvigsson¹,

Fasano²

2012

Ann Nutr Metab

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Breast milk is the natural nutrition for infants, but in the second half of the first year of life, complementary feeding is needed. Many complementary foods contain gluten, but gluten exposure is associated with the risk of developing celiac disease (CD). CD is a disease with considerable morbidity and mortality. Although CD is associated with certain genetic features, carrying the human leukocyte antigen haplotypes DQ2 or DQ8 (a prerequisite for CD development) cannot fully explain who will or who will not develop CD. Potential risk factors for CD include perinatal events and infant feeding practice. With the exception that children who are breastfed at and beyond gluten introduction into the diet probably may be at a lower risk of developing CD, and that heavy gluten load early in life may increase the risk of future CD, data on the impact of infant feeding are inconsistent.

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“…Untreated CD is characterized by autoantibodies to tissue transglutaminase (TG2), an (intestinal) enzyme that binds and modifies gluten peptides, resulting in their improved binding to HLA-DQ2 or HLA-DQ8, the major genetic predisposition for CD, followed by activation and expansion of destructive Th1 T cells in the gut (1). Apart from the established roles of gluten, HLA-DQ2/HLA-DQ8, and TG2, environmental factors such as viral and microbial infections and perhaps feeding practices have also been suggested to contribute to CD pathogenesis (2)(3)(4)(5)(6).…”

mentioning

confidence: 99%

Salivary Gluten Degradation and Oral Microbial Profiles in Healthy Individuals and Celiac Disease Patients

Tian

Faller²,

Leffler

et al. 2017

Appl Environ Microbiol

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Celiac disease (CD) is a chronic immune-mediated enteropathy induced by dietary gluten in genetically predisposed individuals. Saliva harbors the second highest bacterial load of the gastrointestinal (GI) tract after the colon. We hypothesized that enzymes produced by oral bacteria may be involved in gluten processing in the intestine and susceptibility to celiac disease. The aim of this study was to investigate salivary enzymatic activities and oral microbial profiles in healthy subjects versus patients with classical and refractory CD. Stimulated whole saliva was collected from patients with CD in remission (n ϭ 21) and refractory CD (RCD; n ϭ 8) and was compared to healthy controls (HC; n ϭ 20) and subjects with functional GI complaints (n ϭ 12). Salivary gluten-degrading activities were monitored with the tripeptide substrate Z-Tyr-Pro-Gln-pNA and the ␣-gliadin-derived immunogenic 33-mer peptide. The oral microbiome was profiled by 16S rRNA-based MiSeq analysis. Salivary glutenase activities were higher in CD patients compared to controls, both before and after normalization for protein concentration or bacterial load. The oral microbiomes of CD and RCD patients showed significant differences from that of healthy subjects, e.g., higher salivary levels of lactobacilli (P Ͻ 0.05), which may partly explain the observed higher gluten-degrading activities. While the pathophysiological link between the oral and gut microbiomes in CD needs further exploration, the presented data suggest that oral microbe-derived enzyme activities are elevated in subjects with CD, which may impact gluten processing and the presentation of immunogenic gluten epitopes to the immune system in the small intestine.IMPORTANCE Ingested gluten proteins are the triggers of intestinal inflammation in celiac disease (CD). Certain immunogenic gluten domains are resistant to intestinal proteases but can be hydrolyzed by oral microbial enzymes. Very little is known about the endogenous proteolytic processing of gluten proteins in the oral cavity. Given that this occurs prior to gluten reaching the small intestine, such enzymes are likely to contribute to the composition of the gluten digest that ultimately reaches the small intestine and causes CD. We demonstrated that endogenous salivary protease activities are incomplete, likely liberating peptides from larger gluten proteins. The potentially responsible microbes were identified. The study included refractory CD patients, who have been studied less with regard to CD pathogenesis.

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Evidence for the role of a human intestinal adenovirus in the pathogenesis of coeliac disease.

Cited by 213 publications

References 29 publications

Environmental Triggers and Determinants of Type 1 Diabetes

Environmental Triggers and Determinants of Type 1 Diabetes

Timing of Introduction of Gluten and Celiac Disease Risk

Salivary Gluten Degradation and Oral Microbial Profiles in Healthy Individuals and Celiac Disease Patients

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