Article

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: 13.93). 11/2005; 129(4):1294-301. DOI: 10.1053/j.gastro.2005.07.030
Source: PubMed

ABSTRACT 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.

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    • "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). "
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    • "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. "
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    • "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). "
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