Celiac Disease: Caught Between a Rock and a Hard Place

Department of Immunohematology and Blood Transfusion, Leiden University Medical Centre, The Netherlands.
Gastroenterology (Impact Factor: 16.72). 11/2005; 129(4):1294-301. DOI: 10.1053/j.gastro.2005.07.030
Source: PubMed


Celiac disease (CD) is an intestinal disorder caused by an intolerance to gluten, proteins in wheat. CD is an HLA-associated disease: virtually all patients express HLA-DQ2 or HLA-DQ8. Recent work has shown that these disease-predisposing HLA-DQ molecules bind enzymatically modified gluten peptides and these HLA-DQ peptide complexes trigger inflammatory T-cell responses in the small intestine that lead to disease. In addition, gluten induces innate immune responses that contribute to the tissue damage that is characteristic for CD. Thus, CD patients are caught between a rock and a hard place: the disease is caused by a combination of adaptive and innate immune responses that both are triggered by gluten. These findings explain the disease-inducing properties of gluten and provide valuable clues for the development of alternative treatment modalities for patients. They also may be of relevance for our understanding of other multifactorial disorders including IBD and HLA-associated autoimmune diseases.

10 Reads
  • Source
    • "Chronic inflammation is due to the activity of a subgroup of lymphocytes that play a key role in the immune system, particularly in the adaptive immune system: T helper cells that express the surface protein CD4 and are referred to as CD4 1 T cells. The ingestion of wheat gluten and similar proteins in barley and rye activates a T-cell CD4 1 immune response resulting in chronic inflammation and villous atrophy of the small intestine, with impaired absorption of nutrient (Koning, 2005). Characteristic symptoms of celiac disease are chronic diarrhea, weight loss, neurologic symptoms , dermatitis herpetiformis, delayed puberty, osteoporosis, infertility, vitamin and protein deficiencies, and elevated liver enzyme levels (Green, 2005; Krupa- Kozak, 2014), all of which are correlated with a myriad of autoimmune diseases (Cataldo et al., 1997; Cronin and Shanahan, 1997). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Stable isotope analysis in the reconstruction of human palaeodiets can yield clues to early human subsistence strategies, origins and history of farming and pastoralist societies, and intra- and intergroup social differentiation. In the last 10 years, the method has been extended to the pathological investigation. Stable isotope analysis to better understand a diet-related disease: celiac disease in ancient human bones was carried out. To do this, we analyzed the nitrogen and carbon isotopic composition of human (n = 37) and faunal (n = 8) bone remains from the archaeological site of Cosa at Ansedonia, on the Tyrrhenian coast near Orbetello (Tuscany), including the skeletal remains of a young woman (late 1st century–early 2nd century Common Era [CE]) with morphological and genetic features suggestive of celiac disease. We compared the young woman's isotopic data with those of other individuals recovered at the same site but from two later time periods (6th century CE; 11–12th century CE) and with literature data from other Italian archaeological sites dating to the same period. Her collagen δ13C and δ15N values differed from those of the samples at the same site, and from most but not all of the contemporary sites. Although the woman's diet appears distinct, chronic malnutrition resulting from severe malabsorption of essential nutrients due to celiac disease may have affected the isotopic composition of her bone collagen. Am J Phys Anthropol, 2014. © 2014 Wiley Periodicals, Inc.
    American Journal of Physical Anthropology 07/2014; 154(3). DOI:10.1002/ajpa.22517 · 2.38 Impact Factor
  • Source
    • "The active disease component is gliadin [16] with the α-,  β-,  γ-, and ω-fractions. These fractions are rich in proline and glutamine and resistant to enzymatic digestion; large proline/glutamine-rich peptides accumulate in the smallest intestine, triggering an abnormal innate and adaptive immune response in genetically predisposed subjects. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Metabolomics is an "omic" science that is now emerging with the purpose of elaborating a comprehensive analysis of the metabolome, which is the complete set of metabolites (i.e., small molecules intermediates) in an organism, tissue, cell, or biofluid. In the past decade, metabolomics has already proved to be useful for the characterization of several pathological conditions and offers promises as a clinical tool. A metabolomics investigation of coeliac disease (CD) revealed that a metabolic fingerprint for CD can be defined, which accounts for three different but complementary components: malabsorption, energy metabolism, and alterations in gut microflora and/or intestinal permeability. In this review, we will discuss the major advancements in metabolomics of CD, in particular with respect to the role of gut microbiome and energy metabolism.
    02/2014; 2014:756138. DOI:10.1155/2014/756138
  • Source
    • "Celiac disease (CD) is a multifactorial disorder with both genetic and environmental factors implicated in its pathogenesis (1). Gluten, a protein complex formed by glutenin and gliadin proteins, is responsible for immune activation in susceptible individuals (2). In genetically susceptible individuals, CD is triggered by the ingestion of wheat gluten or related rye and barley proteins (3, 4). "
    [Show abstract] [Hide abstract]
    ABSTRACT: This study evaluated serum levels of zinc in patient with CD compare to healthy subjects. Celiac disease (CD) is characterized by small intestinal malabsorption of nutrients as a consequence of ingestion of wheat gluten. Zinc is an essential trace element that it has vital biological functions. Sera of 30 celiac cases and 30 healthy normal cohorts as control group were obtained. Atomic absorption spectrophotometer was employed for estimating serum zinc level. Zinc concentrations in patients diagnosed with CD were significantly lower than healthy subjects (75.97±12 compared with 92.83±18, P-value < 0.0001). The result of this study shows that serum zinc concentration is decreased in celiac patients compare to healthy controls. Serum zinc may thus be a marker of CD in adults presenting with gastrointestinal symptoms.
    Gastroenterology and hepatology from bed to bench 03/2013; 6(2):92-5.
Show more