Article

Clinical practice: Celiac disease

Center for Celiac Research, University of Maryland School of Medicine, Baltimore, MD, USA.
New England Journal of Medicine (Impact Factor: 55.87). 12/2012; 367(25):2419-26. DOI: 10.1056/NEJMcp1113994
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    • "The GI form prevailed among the cases with active disease, which was detected in all the group DS patients and in most of the group DM1 patients, thus contributing to the visible portion of the iceberg. When all forms of the disease were analyzed in combination, the higher prevalence of potential CelD was largely determinant of the large and submerged base of the iceberg (Figure 1), which indicates that the silent form may not be the most frequent, as indicated by previous studies [2] [7] [14] [19] [21]. The disease profile might have changed after the advent of more sensitive and specific serological markers, such as EmA and antitTG , which allow identifying patients with positive antibodies, but still without compatible histopathological findings. "
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    ABSTRACT: The objective of this study is to investigate the occurrence of gastrointestinal (GI) and extraintestinal symptoms in children and adolescents with type 1 diabetes mellitus (DM1) and Down syndrome (DS) and their association with specific antibodies and histopathology of celiac disease (CelD), representing its clinical forms in the iceberg. Cross-sectional study (November 2009-December 2012) conducted at an outpatient care facility in Northeast Brazil including patients [DM1 (n = 111); DS (n = 77)] aged 10 months-18 years old. Measurement of anti-endomysial (EmA) and anti-tissue transglutaminase (anti-tTG) IgA antibodies was performed, as was that of anti-tTG-IgG in the cases with low serum IgA. The patients with antibody positivity were subjected to small intestine biopsy. GI symptoms occurred in 53.7% of the sample, extraintestinal symptoms in 4.3%, and antibody positivity in 28.2% (n = 53). Of those who underwent biopsy (n = 40), histopathological findings of CelD were found in 37.5% [DM1 = 5/111 (4.5%), DS = 10/77 (13.0%)]. GI symptoms were associated with antibody positivity, but not with the histopathology. The GI (32.5%), silent (5.0%), and potential (62.5%) forms of disease were detected. The prevalence of GI symptoms was high in groups DM1 and DS, and the occurrence of such symptoms was associated with antibody positivity. The lack of association between the symptoms and histopatholological findings points to the inconsistency of the former as indicators of CelD. Although the GI form predominated among the cases with active CelD, its contribution to the celiac iceberg was smaller compared with the potential form, which determined the large and submerged base of the iceberg representing the high-risk groups investigated.
    Full-text · Article · Sep 2015 · Scandinavian Journal of Gastroenterology
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    • "Celiac disease (CD) is an intestinal auto-immune disease, the particularity of which is to be triggered by an exogenous antigen composed of peptides from gluten in genetically susceptible individuals[1]. Clinical manifestations vary widely in type and intensity and can lead to severe complications such as osteoporosis or malignant proliferation[2]. The only treatment currently available is a life-long gluten-free diet (GFD). "
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    ABSTRACT: Introduction: The role of serological tests such as IgA anti-transglutaminase autoantibodies has become increasingly important in celiac disease (CD) diagnosis. However, the efficiency of these tests for patient follow-up is controversial. We investigated the correlation of 12 different serological tests, including recent deamidated gliadin and actin IgA tests, with villous atrophy (VA) in a retrospective cohort of treated celiac patients. Materials and methods: Serum samples were collected from 100 treated CD patients who had intestinal biopsy in the course of their follow-up. Antibodies against transglutaminase, deamidated gliadin peptides, and native gliadin were measured, along with IgA anti-actin. The biopsy slides were all blind-reviewed and scored according to Marsh classification. Results: For all deamidated gliadin and transglutaminase tests, we found that a positive result was significantly associated with persistence of intestinal VA, with a diagnostic efficacy up to 80%. Furthermore, antibodies titers directly correlated with the degree of VA, indicating a strong link between disease activity and presence of antibodies in the serum. Interestingly, the tests with the highest association with persistent VA were those for deamidated gliadin IgG. Using a test positivity pattern analysis, we were also able to identify several groups of patients with distinct antibody profiles that showed significant differences in intestinal damage and diet compliance. Conclusions: Altogether, these results show that deamidated gliadin antibodies are strongly correlated with VA and should be considered valuable tools in CD follow-up and that multiplex serologic analysis for treated CD represents a promising tool for personalized patient management.
    Full-text · Article · Sep 2015 · PLoS ONE
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    • "Celiac disease (CD), an autoimmune enteropathy, develops in genetically predisposed individuals after the exposure to gluten-derived peptides [1,2]. CD patients make antibodies specific for gluten peptides, but also for autoantigens, tissue transglutaminase (tTG) being a highly specific autoantigen, and develop enterocytes destruction by CD8 + T cells [2] . "
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    ABSTRACT: Background: TNF-α and IFN-γ play a role in the development of mucosal damage in celiac disease (CD). Polymorphisms of TNFA and IFNG genes, as well as of the TNFRSF1A gene, encoding the TNF-α receptor 1, might underlie different inter-individual disease susceptibility over a common HLA risk background. The aims of this study were to ascertain whether five SNPs in the TNFA promoter (-1031T>C,-857C>T,-376G>A,-308G>A,-238G>A), sequence variants of the TNFRSF1A gene and IFNG +874A>T polymorphism are associated with CD in a HLA independent manner. Methods: 511 children (244 CD, 267 controls) were genotyped for HLA, TNFA and INFG (Real Time PCR). TNFRSF1A variants were studied (DHPLC and sequence). Results: Only the rare TNFA-1031C (OR=0.65, 95% CI:0.44-0.95), -857T (OR=0.42, 95% CI:0.27-0.65), -376A (OR=2.25, 95% CI:1.12-4.51) and -308A (OR=4.76, 95% CI:3.12-7.26) alleles were significantly associated with CD. One TNFRSF1A variant was identified (c.625+10A>G, rs1800693), but not associated with CD. The CD-correlated TNFA SNPs resulted in six haplotypes. Two haplotypes were control-associated (CCGG and TTGG) and three were CD-associated (CCAG, TCGA and CCGA). The seventeen inferred haplotype combinations were grouped (A to E) based on their frequencies among CD. Binary logistic regression analysis documented a strong association between CD and HLA (OR for intermediate risk haplotypes=178; 95% CI:24-1317; OR for high risk haplotypes=2752; 95% CI:287-26387), but also an HLA-independent correlation between CD and TNFA haplotype combination groups. The CD risk for patients carrying an intermediate risk HLA haplotype could be sub-stratified by TNFA haplotype combinations. Conclusion: TNFA promoter haplotypes associate with CD independently from HLA. We suggest that their evaluation might enhance the accuracy in estimating the CD genetic risk.
    Full-text · Article · Apr 2015 · PLoS ONE
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