THE IMPACT OF HLA-DQ TYPING IN CELIAC DISEASE DIAGNOSTIC

Author(s):  
Alessandra Melegari
Keyword(s):  
Hla Dq ◽  
2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Mara Gagliardi ◽  
Nausicaa Clemente ◽  
Romina Monzani ◽  
Luca Fusaro ◽  
Eleonora Ferrari ◽  
...  

AbstractCeliac disease (CD) is a complex immune-mediated chronic disease characterized by a consistent inflammation of the gastrointestinal tract induced by gluten intake in genetically predisposed individuals. Although initiated by the interaction between digestion-derived gliadin, a gluten component, peptides, and the intestinal epithelium, the disorder is highly complex and involving other components of the intestine, such as the immune system. Therefore, conventional model systems, mainly based on two- or three-dimension cell cultures and co-cultures, cannot fully recapitulate such a complex disease. The development of mouse models has facilitated the study of different interacting cell types involved in the disorder, together with the impact of environmental factors. However, such in vivo models are often expensive and time consuming. Here we propose an organ ex vivo culture (gut-ex-vivo system) based on small intestines from gluten-sensitive mice cultivated in a dynamic condition, able to fully recapitulate the biochemical and morphological features of the mouse model exposed to gliadin (4 weeks), in 16 h. Indeed, upon gliadin exposure, we observed: i) a down-regulation of cystic fibrosis transmembrane regulator (CFTR) and an up-regulation of transglutaminase 2 (TG2) at both mRNA and protein levels; ii) increased intestinal permeability associated with deregulated tight junction protein expression; iii) induction and production of pro-inflammatory cytokines such as interleukin (IL)-15, IL-17 and interferon gamma (IFNγ); and iv) consistent alteration of intestinal epithelium/villi morphology. Altogether, these data indicate that the proposed model can be efficiently used to study the pathogenesis of CD, test new or repurposed molecules to accelerate the search for new treatments, and to study the impact of the microbiome and derived metabolites, in a time- and cost- effective manner.


2021 ◽  
Vol 8 ◽  
Author(s):  
Gregory John Tanner

Endopeptidases containing supplements may digest gluten and reduce the impact on celiac and gluten-sensitive subjects who inadvertently consume gluten. We investigated the relative rate of disappearance of coeliac relevant epitopes in extracts of nine commercial supplements, using two competitive enzyme-linked immunosorbent assays (ELISAs)—Ridascreen (detects QQPFP, QQQFP, LQPFP, and QLPFP) and Gluten-Tec (detects Glia-α20 and PFRPQQPYPQ). All epitopes are destroyed by cleavage after P and Q amino acids. Rates at pH 3.5 and pH 7.0 were measured. These experiments were designed to measure relative rates of epitope digestion not to mimic in vivo digestion. The supplements were: 1 GluteGuard, 2 GlutenBlock, 3 GliadinX, 4 GlutnGo, 5 GlutenRescue, 6 Eat E-Z Gluten+, 7 Glutenease, 8 Glutezyme, and 9 Gluten Digest. The mean initial rate and half-lives of epitope digestion were deduced and extrapolated to rates at the recommended dose of one supplement in a fasting stomach volume. At pH 7, supplement 1 was the fastest acting of the supplements, with Ridascreen ELISA, more than twice as fast as the next fastest supplements, 5, 6, 7, and 8. Supplements 2, 3, and 4 showed little activity at pH 7.0. Supplement 1 was also the fastest acting at pH 7 with Gluten-Tec ELISA, more than three times the rate for supplements 2 and 3, with supplements 4–9 showing minimal activity. At pH 3.5, supplement 1 acted more than five times as fast as the next fastest supplements, 2 and 3, when measured by Ridascreen, but supplements 2 and 3 were over two times faster than supplement 1 when measured by Gluten-Tec. Supplements 4–9 demonstrated minimal activity at pH 3.5 with either ELISA. Supplement 1 most rapidly digested the key immuno-reactive gluten epitopes identified by the R5 antibody in the Codex-approved competitive Ridascreen ELISA method and associated with the pathology of celiac disease.


2021 ◽  
Vol 14 ◽  
pp. 117863882110606
Author(s):  
Avinash Lomash ◽  
Anupa Prasad ◽  
Raghvendra Singh ◽  
Somesh Kumar ◽  
Rishi Gupta ◽  
...  

Introduction: Citrulline is regarded as a biomarker for celiac disease (CD). Its utility for assessment and evaluation of additive predictive value for latent, potential CD and first degree relatives (FDRs) needs exploration. Method: Consecutive 558 index cases diagnosed as per European Society for Pediatric Gastroenterology and Nutrition (ESPGHAN) 2012 guidelines and their 1565 FDRs were evaluated over five and half year period. Serology negative FDRs at initial visit and follow ups were served as controls. HLA typing for DQ2 and DQ8 genotypes, along with plasma and dried blood spot (DBS) filter paper citrulline were evaluated. Results: Median plasma citrulline values were 20.1 and 37.33 µMol/l in cases and controls ( P < .001). Cut off values for Marsh grade 3a, 3b, and 3c were 35.0, 32.8, 25.26 µMol/l in CD patients and 36.51, 30.10, 25.26 µMol/l in biopsy proven FDR. Increasing trends of plasma citrulline levels with decreasing tTG-IgA levels were observed on follow up. Low plasma citrulline levels were observed with HLA DQ 2.5 genotype ( P < .05). Agreement between DBS and plasma citrulline was 94.8%. Conclusion: Citrulline is a good surrogate biomarker for identification of histopathological grade of damage, extent of mucosal recovery and has negative correlation with tTG-IgA. It identifies the silent and latent phase of CD. DBS citrulline provides adequate information and can be used for monitoring CD patients at remote locations.


Helicobacter ◽  
2018 ◽  
Vol 23 (2) ◽  
pp. e12465 ◽  
Author(s):  
Maria P. Dore ◽  
Roberta Salis ◽  
Maria F. Loria ◽  
Vincenzo Villanacci ◽  
Gabrio Bassotti ◽  
...  

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Anna Rybak ◽  
Aldona Wierzbicka ◽  
Piotr Socha ◽  
Anna Stolarczyk ◽  
Bożena Cukrowska ◽  
...  

Introduction and Objectives. Celiac disease (CD) is a complex autoimmune disorder occurring in genetically susceptible individuals. There is limited data on the impact of gluten-free diet (GFD) on the risk of developing cardiovascular diseases. Hereby, we present our study regarding the impact of treatment with GFD on the biochemical risk factors of atherosclerosis. Material and Methods. 277 patients with CD from 7 Polish clinics were enrolled in the study (210 children treated for at least 5 years and 67 children included in the study on the day of CD diagnosis and observed for 1 year on a GFD). We obtained selected clinical data, and we assessed lipid profile, apolipoproteins (A1, B, and E), lipoprotein (a), homocysteine, as well as antioxidants (folic and uric acid), and high-sensitivity CRP (hsCRP) for all patients. The compliance to GFD was verified using anti-transglutaminase antibodies and deamidated gliadin peptide antibodies. As a reference group, the data of 95 healthy children recruited for another project was used, for which we had the results of selected parameters. Results. We found significantly lower concentrations of total cholesterol, lipoprotein LDL-C, apolipoproteins A1 and B, as well as hCRP in all children with CD. We showed decreased level (<5 ng/mL) of folic acid among 46% of children treated for >5 years. Moreover, we showed significant decrease of folic acid level already after 1 year of a GFD (12 vs. 5.6 ng/mL; p<0.001). We also found significant negative correlation of z-score body mass index (BMI) with HDL and APOA1 level (r=−0.33; p=0.015 and r=−0.28; p=0.038, respectively) and modest positive correlation of z-score BMI with atherogenic factor of total cholesterol-HDL ratio and LDL-HDL ratio (r=0.40; p=0.002 and r=0.36; p=0.006, respectively). Analysis of physical activity showed an increase in the insulin levels with inactivity (r=0.36; p=0.0025). We also found positive correlation of the sleep duration with the adiponectin level (r=0.41; p=0.011). Conclusions. In children with CD treated with a GFD, decreased level of folic acid together with increased BMI, sedentary behavior, and an improper lipid profile may predispose them to atherosclerosis in the long run. This data suggests the need of further studies to determine the need for metabolic cardiovascular risk screening in children with CD.


2019 ◽  
Vol 35 (1) ◽  
pp. 37-41 ◽  
Author(s):  
Grant L. Hom ◽  
Brian L. Hom ◽  
Barbara Kaplan ◽  
A. David Rothner

Background: Few studies exist examining the frequency of primary headache in children with celiac disease and the impact of a gluten-free diet on primary headache symptomology. This study explores characteristics and frequency of headaches in children with celiac disease and response to gluten-free diet at a single institution. Methods: Medical records were reviewed for children with celiac disease confirmed by the presence of elevated tissue transglutaminase IgA levels and histologic changes consistent with the diagnosis of celiac disease on small bowel biopsy. Eligible participants were contacted via letter for participation in a phone survey regarding headaches. Phone interviews were conducted 2 weeks after notification and lasted approximately 10 minutes. Headaches were classified according to ICHD-3 criteria. Results: 247 eligible patients or their families were contacted. A total of 132 (53.44%) agreed to participate. One participant was excluded due to insufficient information provided. Overall, 51 of 131 participants had recurrent headache defined as at least 1 episode per month (39%, 95% confidence interval [CI]: 31%-47%) and 33 had migraine with or without aura (25%, 95% CI: 18%-33%). Twenty-eight had frequent tension-type headache (22%, 95% CI: 15%-29%). Thirty-two participants noted headaches before a confirmed diagnosis of celiac disease. Twenty-two of 32 participants (68.75%) noticed decreased headache frequency or intensity, or both, after starting the gluten-free diet. Conclusion: This study suggests that at least one-third of children and adolescents with celiac disease have recurrent headaches at the time of diagnosis. A gluten-free diet led to improved headache symptomology in a significant number of these patients.


2015 ◽  
Vol 34 (2) ◽  
pp. 112-116 ◽  
Author(s):  
Bisman Khurana ◽  
Avinash Lomash ◽  
Sumaira Khalil ◽  
Malvika Bhattacharya ◽  
K. Rajeshwari ◽  
...  

2014 ◽  
Vol 46 ◽  
pp. e109
Author(s):  
Silvia Nastasio ◽  
Lorenza Lepore ◽  
Elena Chiocca ◽  
Giulia Marsalli ◽  
Silvia Ghione ◽  
...  

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Eva Turk ◽  
Dušanka Mičetić-Turk ◽  
Maja Šikić-Pogačar ◽  
Alojz Tapajner ◽  
Veljko Vlaisavljević ◽  
...  

Abstract Background Measurements of health-related quality of life (HRQoL) among celiac disease patients using a validated questionnaire have been lacking in Slovenia. This study aims to measure HRQoL in celiac disease (CD) patients using EQ-5D internationally validated questionnaire and comparing it to the HRQoL of the general population. Methods In this cross sectional analysis all of the approximately 2000 members of the Slovenian Celiac Society were invited to take part. We used a 3 step approach for recruitment and data collection. HRQoL was evaluated through the EuroQoL EQ-5D-5L instrument (Slovenian version) and analysed using the ordinal logistic regression. Results Out of 321 patients who gave their consent, 247 celiac patients were included in the study (77%). 68% of the participants were female and 53% of them lived in an urban setting. Most patients originated from North-East Slovenia, whereas approximately 30% of patients came from other Slovenian regions. The EQ-5D respondents’ self-reported health status at the time of the study show that most patients have slight or no problems when living with CD. The duration of the gluten-free diet, academic education and rare (< 1 × year) doctor visits affect EQ-5D in a positive way. On the other hand, higher age and chronic rheumatic disease were negatively associated with EQ-5D also when compared to the general population. Conclusion This is the first Slovenian study to measure the HRQoL of Slovenian CD patients, using an internationally validated questionnaire. The results of our study show that HRQoL is slightly impaired among Slovenian patients with CD. Clinical characteristics are better determinants of their HRQoL than socio-demographic factors. Greater awareness of the impact of CD on patients’ HRQoL would improve the holistic management of CD patients.


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