The Spectrum of Differences between Childhood and Adulthood Celiac Disease

Ciccocioppo, Rachele; Kružliak, Peter; Cangemi, Giuseppina Cristina; Pohanka, Miroslav; Betti, E.; Lauret, Eugenia; Rodrigo, Luís

doi:10.3390/nu7105426

Cited by 58 publications

(49 citation statements)

References 177 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The 2013 rate was 50 new cases per 100,000 person years for children and adolescents below 18 years of age. CD prevalence is higher in children with conditions such as type I diabetes, Down syndrome, and autoimmune thyroid disease 33 .…”

Section: Epidemiologymentioning

confidence: 98%

Biomarkers of Inflammation and Intestinal Mucosa Pathology in Celiac Disease

Bragde

2019

Linköping University Medical Dissertations

View full text Add to dashboard Cite

Celiac disease (CD) is a chronic small intestinal immune-mediated enteropathy triggered by gluten. The only currently available treatment is complying with a lifelong gluten-free diet, which should not be commenced before a CD diagnosis has been established by diagnostic test results (including histopathologic assessment of small intestinal biopsies and CD-specific antibody levels). This makes diagnostic swiftness and accuracy important. In cases with low CD-specific antibody levels and/or low-grade intestinal injuries the diagnosis can be difficult to establish. The main objective of this thesis was to complement and improve CD diagnostics by identifying and implementing new biomarkers, mainly based on gene expression, in small intestinal biopsies and blood. In paper I, genes were selected to reflect villous height, crypt elongation, immune response, and epithelial integrity. The results showed that a subset of those genes could discriminate active CD mucosa from mucosa without CD-related changes and grade the intestinal injury. In paper III, an unbiased investigation of gene expression in CD mucosa was performed using transcriptome analysis. Active CD and non-CD mucosa showed differential expression in a subset of genes, and some were differentially expressed in CD mucosa before histopathologic assessment could confirm intestinal alterations compatible with a CD diagnosis. Gene set analysis revealed that there are many biological processes affected in CD mucosa, including those associated with immune response, microbial infection, phagocytosis, intestinal barrier function, metabolism, and transportation. In parallel, gene expression was investigated in stabilised whole blood. Blood is a more accessible sampling material than intestinal biopsies, and stabilised blood is suitable for routine diagnostics since transcript levels are preserved at sampling. In paper II, expressions from a selection of genes were quantified in stabilised whole blood (RNA) and/or plasma (protein). Three genes with differential expression in CD were identified. Compared to the CD-specific autoantibodies against tissue transglutaminase (anti-TG2) alone, the addition of the information from the new potential markers resulted in a non-significant contribution to the diagnostic capacity of anti-TG2. An unbiased investigation using transcriptome analysis (paper IV) showed that gene level expression differences in stabilised whole blood were small between CD and non-CD. However, expression differences on a gene set level could potentially be used in CD diagnostics. CD-associated biological processes suggested UBD ubiquitin D ULN upper limit of normal ZFR zinc finger RNA binding protein Contents ix Contents Introduction .

show abstract

Section: Epidemiologymentioning

confidence: 98%

Biomarkers of Inflammation and Intestinal Mucosa Pathology in Celiac Disease

Bragde

2019

Linköping University Medical Dissertations

View full text Add to dashboard Cite

show abstract

“…But, according to the current ESPGHAN recommendations, in symptomatic children, if there is positive anti-endomysium antibodies (anti-EMA) and anti-tissue transglutaminase (anti-tTG) IgA antibody titers more than 10 times the normal with positive HLA DQ2/8, then intestinal biopsy can be avoided [2]. The anti-tTG IgA antibodies titer and histological lesions have an inverse correlation with the age [23]. Thus, as the age of presentation increases, the antibody titers decrease and the histological lesions become less evident [22].…”

Section: Diagnostic Testsmentioning

confidence: 99%

Immunopathogenesis and therapeutic approaches in pediatric celiac disease

Agarwal

Kovilam

Zach

et al. 2016

Expert Review of Clinical Immunology

View full text Add to dashboard Cite

Summary Celiac Disease is an autoimmune enteropathy with increasing incidence worldwide in both adults and children. It occurs as an inflammatory condition with destruction of the normal architecture of villi on consumption of gluten and related protein products found in wheat, barley and rye. However, the exact pathogenesis is not yet fully understood. A gluten-free diet remains the main modality of therapy to date. While some patients continue to have symptoms even on a gluten-free diet, adherence to this diet is also difficult, especially for the children. Hence, there is continued interest in novel methods of therapy and the current research focus is on the promising novel non-dietary modalities of treatment. Here, we critically reviewed the existing literature regarding the pathogenesis of celiac disease in children including the role of in-utero exposure leading to neonatal and infant sensitization and its application for the development of new therapeutic approaches for these patients.

show abstract

“…It can, therefore, be used as a tool for negative screening in risk groups or to confirm a diagnosis in doubtful, subclinical cases, which represent the majority. The coincidence of CD with T1D for different populations is widely known-according to various sources, it oscillates around 6-15% [4][5][6][7][8], albeit it is very problematic to make a proper diagnosis in asymptomatic patients, mostly due to inconclusive results of small intestine biopsies [3,4,9] and the phenomenon of negative seroconversion [10] (decrease in tTG antibody levels, despite the lack of a gluten-free diet).…”

Section: Introductionmentioning

confidence: 99%

The Usefulness of Genotyping of Celiac Disease-Specific HLA among Children with Type 1 Diabetes in Various Clinical Situations

Deja

Sikora

Pyziak-Skupień

et al. 2020

Journal of Diabetes Research

View full text Add to dashboard Cite

Aim. The aim of the study was to determine the usefulness of HLA DQ2/DQ8 genotyping in children with T1D in various clinical situations: as a screening test at the diabetes onset, as a verification of the diagnosis in doubtful situations, and as a test estimating the risk of CD in the future. Materials and methods. Three groups of patients with T1D were included: newly diagnosed (n=92), with CD and villous atrophy (n=30), and with potential CD (n=23). Genetic tests were performed (commercial test, PCR, and REX), and clinical data were collected. Results. The results of genetic tests confirmed the presence of DQ2/DQ8 in 94% of children with diabetes (group I) and in 100% of children with diabetes and CD (groups II and III, respectively). Comparative analysis of the HLA DQ2/DQ8 distribution did not show any differences. Allele DRB1∗04 (linked with HLA DQ8) was significantly less common in children with diabetes and CD (group I versus groups II and III, 56.5% vs. 24.5%; p=0.001). The probability of developing CD in DRB1∗04-positive patients was 4 times lower (OR 0.25; 95% CI 0.118-0.529; p=0.001). DRB1∗04 was significantly less frequent in children with villous atrophy compared to potential CD (13% vs. 39%; p=0.03). Conclusions. Genotyping HLA DQ2/DQ8 as a negative screening has limited use in assessing the risk of CD at the diabetes onset and does not allow to verify the diagnosis of CD in doubtful situations. The presence of the DRB1∗04 allele modulates the risk of CD and significantly reduces it and can predict a potential form.

show abstract

The Spectrum of Differences between Childhood and Adulthood Celiac Disease

Cited by 58 publications

References 177 publications

Biomarkers of Inflammation and Intestinal Mucosa Pathology in Celiac Disease

Biomarkers of Inflammation and Intestinal Mucosa Pathology in Celiac Disease

Immunopathogenesis and therapeutic approaches in pediatric celiac disease

The Usefulness of Genotyping of Celiac Disease-Specific HLA among Children with Type 1 Diabetes in Various Clinical Situations

Contact Info

Product

Resources

About