Predictors of Family Risk for Celiac Disease: A Population-Based Study

Rubio–Tapia, Alberto; Dyke, Carol T. Van; Lahr, Brian D.; Zinsmeister, Alan R.; El–Youssef, Mounif; Moore, S. Breanndan; Bowman, Martha; Burgart, Lawrence J.; Melton, L. Joseph; Murray, Joseph A.

doi:10.1016/j.cgh.2008.04.008

Cited by 138 publications

(149 citation statements)

References 34 publications

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“…Early introduction of gluten while infants are not breast-fed, frequent episodes of gastroenteritis before age 6 mo, homozygosity for HLA-DQ2, and a first-degree relative having CD are among the strongest factors predicting development of CD (2,31,35,36). Presumably, these factors influence the priming, expansion and/or maintenance of HLA-DQ2-restricted CD4 ϩ Th1 cells specific for deamidated gluten found in established CD.…”

Section: Discussionmentioning

confidence: 99%

Resistance to Celiac Disease in Humanized HLA-DR3-DQ2-Transgenic Mice Expressing Specific Anti-Gliadin CD4+ T Cells

Kauwe

Chen

Anderson

et al. 2009

The Journal of Immunology

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Celiac disease is a chronic inflammatory enteropathy caused by cellular immunity to dietary gluten. More than 90% of patients carry HLA-DQ2 encoded by HLA-DQA1*05 and DQB1*02, and gluten-specific CD4+ T cells from intestinal biopsies of these patients are HLA-DQ2-restricted, produce Th1 cytokines and preferentially recognize gluten peptides deamidated by tissue transglutaminase. We generated mice lacking murine MHC class II genes that are transgenic for human CD4 and the autoimmunity and celiac disease-associated HLA-DR3-DQ2 haplotype. Immunization with the α-gliadin 17-mer that incorporates the overlapping DQ2-α-I and DQ2-α-II epitopes immunodominant in human celiac disease generates peptide-specific HLA-DQ2-restricted CD4+ T cells. When exposed to dietary gluten, naive or gliadin-primed mice do not develop pathology. Coincident introduction of dietary gluten and intestinal inflammation resulted in low-penetrance enteropathy and tissue transglutaminase-specific IgA. Two further strains of transgenic mice expressing HLA-DR3-DQ2 and human CD4, one with a NOD background and another TCR transgenic having over 90% of CD4+ T cells specific for the DQ2-α-II epitope with a Th1 phenotype, were also healthy when consuming gluten. These humanized mouse models indicate that gluten ingestion can be tolerated without intestinal pathology even when HLA-DQ2-restricted CD4+ T cell immunity to gluten is established, thereby implicating additional factors in controlling the penetrance of celiac disease.

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Section: Discussionmentioning

confidence: 99%

Resistance to Celiac Disease in Humanized HLA-DR3-DQ2-Transgenic Mice Expressing Specific Anti-Gliadin CD4+ T Cells

Kauwe

Chen

Anderson

et al. 2009

The Journal of Immunology

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“…The estimated prevalence of CD in first-degree relatives living in Minneapolis, USA is 11% of all affec ted family members who carried at-risk genotypes (HLA-DQ2 in more than 90% of c ases, and the remainder c arrying HLA-DQ8). About half of these persons have c linic ally "silent disease", and yet, their small bowel biopsies may show severe arc hitec tural c hanges [6] . This apparent disc onnec tion in some patients between severity of symptoms with CD and the severity of histologic al abnormalities (typic ally defined in the proximal small bowel) may reflect the variable extent of histologic al involvement further along the length of the small intestine.…”

Section: Epidemiologymentioning

confidence: 99%

Recent advances in celiac disease

Freeman

Chopra²,

Clandinin³

et al. 2011

WJG

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Celiac disease now affects about one person in a hundred in Europe and North America. In this review, we consider a number of important and exciting recent developments, such as clinical associations, HLA-DQ2 and HLA-DQ8 predispositions, the concept of potential celiac disease, the use of new imaging/endoscopy techniques, and the development of refractory disease. This review will be of use to all internists, pediatricians and gastroenterologists.

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“…Malabsorption of important nutrient such as vitamin b12, calcium, and iron is common and along with the diarrhea and weight loss may be some of the reasons that patients with CD have growth issues and tend to be short in stature [7,8,9,10]. Evidence supports the theory that CD can be hereditary and occurs in patients who have Human Leukocyte Antigens (HLA) HLA-DQ2 and HLADQ8 haplotypes [11,12,13]. In severe cases, CD can lead to digestive cancers which can be fatal [14].…”

Section: Introductionmentioning

confidence: 66%