scholarly journals Presence of DQ2.2 Associated with DQ2.5 Increases the Risk for Celiac Disease

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Lucas Malta Almeida ◽  
Lenora Gandolfi ◽  
Riccardo Pratesi ◽  
Rosa Harumi Uenishi ◽  
Fernanda Coutinho de Almeida ◽  
...  
Keyword(s):  
At Risk ◽  
T Cells ◽  
Celiac Disease ◽  
Disease Risk ◽  
Disease Development ◽  
Immunogenic Peptides ◽  
Immune Mediated ◽  
Hla Dq ◽  
Genetically Determined

Background. Celiac disease (CD) is a genetically determined immune-mediated disorder in which gluten immunogenic peptides are presented to CD4 T cells by HLA-DQ2.5, DQ8, DQ2.2, and their combinations. Our aim is to establish a risk gradient for celiac disease based on HLA-DQ profile in a brazilian representative population and the relevance of DQ2.2 in celiac disease development. Materials and Methods. 237 celiac patients and 237 controls (both groups with 164 females and 73 males) were included. All samples were tested for the presence of predisposing HLA-DQ alleles using the PCR-SSP method. Results were considered significant when p<0.05. Disease risk was expressed as 1 : N for each HLA-DQ category described at this study. Results. DQ2.5 and/or DQ8 were detected in 224 celiac patients (94.5%) and 84 controls (35.4%). Eight celiac patients (3.4%) and 38 controls (16%) disclosed only DQ2.2. Even though DQ2.2 (β2/β2 or β2/x) showed a low CD risk of 1 : 251 and 1 : 550, respectively, the genotype DQ2.5/DQ2.2 (β2/β2) showed high CD risk of 1 : 10 (p<0.0001). The disease risk gradient ranged from 1 : 3014 to 1 : 7. Conclusion. Our study allowed the determination of a risk gradient for celiac disease development in at-risk population, showing that DQ2.2 variant was relevant when associated with DQ2.5.

Celiac disease risk stratification based on HLA-DQ heterodimer (HLA-DQA1 ~ DQB1) typing in a large cohort of adults with suspected celiac disease

2020 ◽  
Vol 81 (2-3) ◽  
pp. 59-64 ◽  
Author(s):  
Rok Seon Choung ◽  
John R. Mills ◽  
Melissa R. Snyder ◽  
Joseph A. Murray ◽  
Manish J. Gandhi
Keyword(s):  
Celiac Disease ◽  
Risk Stratification ◽  
Disease Risk ◽  
Large Cohort ◽  
Hla Dq ◽  
Hla Dqa1

scholarly journals Celiac Disease Risk Determined By HLA-DQ Genotype Protects Against Gvhd in a Dose-Responsive Manner

2020 ◽  
Vol 26 (3) ◽  
pp. S186
Author(s):  
Susan McClory ◽  
Viviane C. Cahen ◽  
Yimei Li ◽  
Jamie L. Duke ◽  
Dimitri S. Monos ◽  
...  
Keyword(s):  
Celiac Disease ◽  
Disease Risk ◽  
Hla Dq

T cells recognize a peptide derived from α-gliadin presented by the celiac disease-associated HLA-DQ (α1∗0501, β1∗0201) heterodimer

1994 ◽  
Vol 39 (4) ◽  
pp. 243-252 ◽  
Author(s):  
Henrik A. Gjertsen ◽  
Knut E.A. Lundin ◽  
Ludvig M. Sollid ◽  
Jon A. Eriksen ◽  
Erik Thorsby
Keyword(s):  
T Cells ◽  
Celiac Disease ◽  
Hla Dq

scholarly journals Determination of gluten immunogenic peptides for the management of the treatment adherence of celiac disease: A systematic review

2021 ◽  
Vol 27 (37) ◽  
pp. 6306-6321
Author(s):  
Laura Coto ◽  
Irati Mendia ◽  
Carolina Sousa ◽  
Julio César Bai ◽  
Angel Cebolla
Keyword(s):  
Systematic Review ◽  
Celiac Disease ◽  
Treatment Adherence ◽  
Immunogenic Peptides

scholarly journals Gliadin-specific, HLA-DQ(alpha 1*0501,beta 1*0201) restricted T cells isolated from the small intestinal mucosa of celiac disease patients.

1993 ◽  
Vol 178 (1) ◽  
pp. 187-196 ◽  
Author(s):  
K E Lundin ◽  
H Scott ◽  
T Hansen ◽  
G Paulsen ◽  
T S Halstensen ◽  
...  
Keyword(s):  
T Cells ◽  
Celiac Disease ◽  
T Cell ◽  
Small Intestinal Mucosa ◽  
Hla Association ◽  
T Cell Clones ◽  
Cell Clones ◽  
Hla Dq ◽  
Small Intestinal

Celiac disease (CD) is most probably an immunological disease, precipitated in susceptible individuals by ingestion of wheat gliadin and related proteins from other cereals. The disease shows a strong human HLA association predominantly to the cis or trans encoded HLA-DQ(alpha 1*0501,beta 1*0201) (DQ2) heterodimer. T cell recognition of gliadin presented by this DQ heterodimer may thus be of immunopathogenic importance in CD. We therefore challenged small intestinal biopsies from adult CD patients on a gluten-free diet in vitro with gluten (containing both gliadin and other wheat proteins), and isolated activated CD25+ T cells. Polyclonal T cell lines and a panel of T cell clones recognizing gluten were established. They recognized the gliadin moiety of gluten, but not proteins from other cereals. Inhibition studies with anti-HLA antibodies demonstrated predominant antigen presentation by HLA-DQ molecules. The main antigen-presenting molecule was established to be the CD-associated DQ(alpha 1*0501, beta 1*0201) heterodimer. The gluten-reactive T cell clones were CD4+, CD8-, and carried diverse combinations of T cell receptor (TCR) V alpha and V beta chains. The findings suggest preferential mucosal presentation of gluten-derived peptides by HLA-DQ(alpha 1*0501, beta 1*0201) in CD, which may explain the HLA association.

scholarly journals HLA-DQA1 and HLA-DQB1 Alleles, Conferring Susceptibility to Celiac Disease and Type 1 Diabetes, are More Expressed Than Non-Predisposing Alleles and are Coordinately Regulated

Cells ◽  
2019 ◽  
Vol 8 (7) ◽  
pp. 751 ◽  
Author(s):  
Farina ◽  
Picascia ◽  
Pisapia ◽  
Barba ◽  
Vitale ◽  
...  
Keyword(s):  
T Cells ◽  
Type 1 Diabetes ◽  
Celiac Disease ◽  
Cd4 T Cells ◽  
High Expression ◽  
Transcriptional Level ◽  
Risk Alleles ◽  
Hla Dq ◽  
Hla Dqa1

HLA DQA1*05 and DQB1*02 alleles encoding the DQ2.5 molecule and HLA DQA1*03 and DQB1*03 alleles encoding DQ8 molecules are strongly associated with celiac disease (CD) and type 1 diabetes (T1D), two common autoimmune diseases (AD). We previously demonstrated that DQ2.5 genes showed a higher expression with respect to non-CD associated alleles in heterozygous DQ2.5 positive (HLA DR1/DR3) antigen presenting cells (APC) of CD patients. This differential expression affected the level of the encoded DQ2.5 molecules on the APC surface and established the strength of gluten-specific CD4+ T cells response. Here, we expanded the expression analysis of risk alleles in patients affected by T1D or by T1D and CD comorbidity. In agreement with previous findings, we found that DQ2.5 and DQ8 risk alleles are more expressed than non-associated alleles also in T1D patients and favor the self-antigen presentation. To investigate the mechanism causing the high expression of risk alleles, we focused on HLA DQA1*05 and DQB1*02 alleles and, by ectopic expression of a single mRNA, we modified the quantitative equilibrium among the two transcripts. After transfection of DR7/DR14 B-LCL with HLA-DQA1*05 cDNA, we observed an overexpression of the endogenous DQB1*02 allele. The DQ2.5 heterodimer synthesized was functional and able to present gluten antigens to cognate CD4+ T cells. Our results indicated that the high expression of alpha and beta transcripts, encoding for the DQ2.5 heterodimeric molecules, was strictly coordinated by a mechanism acting at a transcriptional level. These findings suggested that, in addition to the predisposing HLA-DQ genotype, also the expression of risk alleles contributed to the establishment of autoimmunity.

scholarly journals Dynamics and Considerations in the Determination of the Excretion of Gluten Immunogenic Peptides in Urine: Individual Variability at Low Gluten Intake

Nutrients ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 2624
Author(s):  
Laura Coto ◽  
Carolina Sousa ◽  
Angel Cebolla
Keyword(s):  
Celiac Disease ◽  
False Negative ◽  
Individual Variability ◽  
Lateral Flow Immunoassay ◽  
Gluten Free ◽  
Negative Results ◽  
Immunogenic Peptides ◽  
False Negative Results ◽  
Healthy Participants

Background: A lifelong strict gluten-free diet is the only available treatment for celiac disease, but total exclusion of gluten is difficult to achieve. The aim of this study was to determine the range of time and the amount of gluten immunogenic peptides (GIP) excreted in urine after specific gluten ingestions. Methods: 20 healthy participants followed the same diet for 12 days in which 50 mg and 2 g of gluten were ingested and all the urinations were collected. GIP were analyzed by lateral flow immunoassay (LFIA) tests and quantified using an LFIA reader. Results: GIP were detected in 15% and 95% of participants after 50 mg and 2 g gluten intakes, respectively. The higher frequency and concentration of GIP was found between 6 and 9 h after both gluten ingestions. The ranges of detection were 3–12 h (50 mg) and 0–15 h (2 g). Conclusions: An increase in the frequency of urine tests may be a suitable approach to avoid false negative results. The use of the LFIA test in three urine samples collected at different times may show a sensitivity of 19.6% for a gluten ingestion like 50 mg, increasing to 93% after 2 g consumption.

scholarly journals Challenges of Monitoring the Gluten-Free Diet Adherence in the Management and Follow-Up of Patients with Celiac Disease

Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2274
Author(s):  
Herbert Wieser ◽  
Ángela Ruiz-Carnicer ◽  
Verónica Segura ◽  
Isabel Comino ◽  
Carolina Sousa
Keyword(s):  
Celiac Disease ◽  
Clinical Symptoms ◽  
Poor Quality ◽  
Gluten Free Diet ◽  
Gluten Free ◽  
Free Products ◽  
Immunogenic Peptides ◽  
Immune Mediated ◽  
Strict Diet

Celiac disease (CD) is a chronic gluten-responsive immune mediated enteropathy and is treated with a gluten-free diet (GFD). However, a strict diet for life is not easy due to the ubiquitous nature of gluten. This review aims at examining available evidence on the degree of adherence to a GFD, the methods to assess it, and the barriers to its implementation. The methods for monitoring the adherence to a GFD are comprised of a dietary questionnaire, celiac serology, or clinical symptoms; however, none of these methods generate either a direct or an accurate measure of dietary adherence. A promising advancement is the development of tests that measure gluten immunogenic peptides in stools and urine. Causes of adherence/non-adherence to a GFD are numerous and multifactorial. Inadvertent dietary non-adherence is more frequent than intentional non-adherence. Cross-contamination of gluten-free products with gluten is a major cause of inadvertent non-adherence, while the limited availability, high costs, and poor quality of certified gluten-free products are responsible for intentionally breaking a GFD. Therefore, several studies in the last decade have indicated that many patients with CD who follow a GFD still have difficulty controlling their diet and, therefore, regularly consume enough gluten to trigger symptoms and damage the small intestine.

scholarly journals The Interaction among Microbiota, Immunity, and Genetic and Dietary Factors Is theCondicio Sine Qua NonCeliac Disease Can Develop

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
D. Pagliari ◽  
R. Urgesi ◽  
S. Frosali ◽  
M. E. Riccioni ◽  
E. E. Newton ◽  
...  
Keyword(s):  
Celiac Disease ◽  
Wheat Gluten ◽  
Signs And Symptoms ◽  
Dietary Factors ◽  
Mucosal Barrier ◽  
Genetic Determination ◽  
Immune Mediated ◽  
Hla Dq ◽  
Mucosal Barrier Function ◽  
Environmental Trigger

Celiac disease (CD) is an immune-mediated enteropathy, triggered by dietary wheat gluten and similar proteins of barley and rye in genetically susceptible individuals. This is a complex disorder involving both environmental and immune-genetic factors. The major genetic risk factor for CD is determined by HLA-DQ genes. Dysfunction of the innate and adaptive immune systems can conceivably cause impairment of mucosal barrier function and development of localized or systemic inflammatory and autoimmune processes. Exposure to gluten is the main environmental trigger responsible for the signs and symptoms of the disease, but exposure to gluten does not fully explain the manifestation of CD. Thus, both genetic determination and environmental exposure to gluten are necessary for the full manifestation of CD; neither of them is sufficient alone. Epidemiological and clinical data suggest that other environmental factors, including infections, alterations in the intestinal microbiota composition, and early feeding practices, might also play a role in disease development. Thus, this interaction is thecondicio sine qua nonceliac disease can develop. The breakdown of the interaction among microbiota, innate immunity, and genetic and dietary factors leads to disruption of homeostasis and inflammation; and tissue damage occurs. Focusing attention on this interaction and its breakdown may allow a better understanding of the CD pathogenesis and lead to novel translational avenues for preventing and treating this widespread disease.

scholarly journals Influence of Environmental and Genetic Factors Linked to Celiac Disease Risk on Infant Gut Colonization by Bacteroides Species

2011 ◽  
Vol 77 (15) ◽  
pp. 5316-5323 ◽  
Author(s):  
Ester Sánchez ◽  
Giada De Palma ◽  
Amalia Capilla ◽  
Esther Nova ◽  
Tamara Pozo ◽  
...  
Keyword(s):  
Celiac Disease ◽  
Genetic Risk ◽  
Disease Risk ◽  
Feeding Practice ◽  
Content Type ◽  
High Genetic Risk ◽  
Gut Colonization ◽  
Hla Dq ◽  
Breast Fed ◽  
Milk Feeding

ABSTRACTCeliac disease (CD) is an immune-mediated enteropathy involving genetic and environmental factors whose interaction might influence disease risk. The aim of this study was to determine the effects of milk-feeding practices and the HLA-DQ genotype on intestinal colonization ofBacteroidesspecies in infants at risk of CD development. This study included 75 full-term newborns with at least one first-degree relative suffering from CD. Infants were classified according to milk-feeding practice (breast-feeding or formula feeding) and HLA-DQ genotype (high or low genetic risk). Stools were analyzed at 7 days, 1 month, and 4 months by PCR and denaturing gradient gel electrophoresis (DGGE). TheBacteroidesspecies diversity index was higher in formula-fed infants than in breast-fed infants. Breast-fed infants showed a higher prevalence ofBacteroides uniformisat 1 and 4 months of age, while formula-fed infants had a higher prevalence ofB. intestinalisat all sampling times, ofB. caccaeat 7 days and 4 months, and ofB. plebeiusat 4 months. Infants with high genetic risk showed a higher prevalence ofB. vulgatus, while those with low genetic risk showed a higher prevalence ofB. ovatus,B. plebeius, andB. uniformis. Among breast-fed infants, the prevalence ofB. uniformiswas higher in those with low genetic risk than in those with high genetic risk. Among formula-fed infants, the prevalence ofB. ovatusandB. plebeiuswas increased in those with low genetic risk, while the prevalence ofB. vulgatuswas higher in those with high genetic risk. The results indicate that both the type of milk feeding and the HLA-DQ genotype influence the colonization process ofBacteroidesspecies, and possibly the disease risk.

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