Recent PubMed Articles on Coeliac Disease (External)

Maternal genetic markers for risk of celiac disease and their potential association with neural tube defects in offspring.

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Maternal genetic markers for risk of celiac disease and their potential association with neural tube defects in offspring.

Mol Genet Genomic Med. 2019 Apr 09;:e688

Authors: Hoang TT, Lei Y, Mitchell LE, Sharma SV, Swartz MD, Waller DK, Finnell RH, Benjamin RH, Browne ML, Canfield MA, Lupo PJ, McKenzie P, Shaw GM, Agopian AJ, National Birth Defects Prevention Study

Abstract
BACKGROUND: We examined the association between the maternal genotype for celiac disease-associated variants and risk of neural tube defects (NTDs).
METHODS: We conducted a case-control study, using data from the National Birth Defects Prevention Study. We evaluated 667 cases (women with an offspring with NTD) and 743 controls (women with an offspring without a birth defect). We classified women as having low, intermediate, or high risk of celiac disease based on human leukocyte antigen (HLA) variants. We used logistic regression to assess the relationship between HLA celiac risk group (low, intermediate, high) and risk of NTDs. Fifteen non-HLA variants (identified from genome-wide association studies of celiac disease) were individually evaluated and modeled additively.
RESULTS: There was no association between HLA celiac risk group and NTDs (intermediate vs. low risk: aOR, 1.0; 95% CI, 0.8-1.3; high vs. low risk: aOR, 0.8; 95% CI, 0.5-1.3). Of the fifteen non-HLA variants, we observed five significant associations after accounting for multiple comparisons. Three negative associations were observed with rs10903122, rs13314993, rs13151961 (aOR range: 0.69-0.81), and two positive associations were observed with rs13003464 and rs11221332 (aOR range: 1.27-1.73).
CONCLUSION: If confirmed, our results suggest that the maternal variants related to celiac disease may be involved in the risk of NTDs.

PMID: 30968606 [PubMed - as supplied by publisher]

The Profile of Urinary Headspace Volatile Organic Compounds After 12-Week Intake of Oligofructose-Enriched Inulin by Children and Adolescents with Celiac Disease on a Gluten-Free Diet: Results of a Pilot, Randomized, Placebo-Controlled Clinical Trial.

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The Profile of Urinary Headspace Volatile Organic Compounds After 12-Week Intake of Oligofructose-Enriched Inulin by Children and Adolescents with Celiac Disease on a Gluten-Free Diet: Results of a Pilot, Randomized, Placebo-Controlled Clinical Trial.

Molecules. 2019 Apr 05;24(7):

Authors: Drabińska N, Jarocka-Cyrta E, Ratcliffe NM, Krupa-Kozak U

Abstract
The concentration of volatile organic compounds (VOCs) can inform about the metabolic condition of the body. In the small intestine of untreated persons with celiac disease (CD), chronic inflammation can occur, leading to nutritional deficiencies, and consequently to functional impairments of the whole body. Metabolomic studies showed differences in the profile of VOCs in biological fluids of patients with CD in comparison to healthy persons; however, there is scarce quantitative and nutritional intervention information. The aim of this study was to evaluate the effect of the supplementation of a gluten-free diet (GFD) with prebiotic oligofructose-enriched inulin (Synergy 1) on the concentration of VOCs in the urine of children and adolescents with CD. Twenty-three participants were randomized to the group receiving Synergy 1 (10 g per day) or placebo for 12 weeks. Urinary VOCs were analyzed using solid-phase microextraction and gas chromatography⁻mass spectrometry. Sixteen compounds were identified and quantified in urine samples. The supplementation of GFD with Synergy 1 resulted in an average concentration drop (36%) of benzaldehyde in urine samples. In summary, Synergy 1, applied as a supplement of GFD for 12 weeks had a moderate impact on the VOC concentrations in the urine of children with CD.

PMID: 30959740 [PubMed - in process]

Risk of Eating Disorders in Patients With Celiac Disease.

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Risk of Eating Disorders in Patients With Celiac Disease.

J Pediatr Gastroenterol Nutr. 2018 01;66(1):53-57

Authors: Babio N, Alcázar M, Castillejo G, Recasens M, Martínez-Cerezo F, Gutiérrez-Pensado V, Vaqué C, Vila-Martí A, Torres-Moreno M, Sánchez E, Barrubés L, Salas-Salvadó J

Abstract
OBJECTIVES: Several cases of eating disorders (EDs) have been reported in patients with celiac disease (CD), suggesting that ED could be a comorbidity associated with CD. Few epidemiological studies have, however, assessed this potential association. We aimed to evaluate the risk of EDs in individuals diagnosed with CD in comparison to healthy controls.
METHODS: A total of 98 cases and 98 controls matched for sex, age, and body mass index between 10 and 23 years old were studied. A questionnaire was completed on medical history and sociodemographic as well as anthropometric characteristics. Various ED screening self-reported tests were administered.
RESULTS: A total of 61.2% of the study population were girls with a mean age of 15.3 ± 3.7 years old. Patients with CD scored nonsignificantly higher on all the ED screening tests than control participants. No differences were observed between study groups in terms of the frequency of individuals who exceeded the clinical cutoff identifying those at risk of ED. Patients with CD above 13 years old were associated with a 2.15-point increase in the Eating Attitude Test score compared with controls [β-coefficient = 2.15 SE 1.04; P = 0.04] after adjusting for various confounders.
CONCLUSIONS: Although being a patient with CD was associated with a significantly higher Eating Attitude Test score in individuals older than 13 years old, no clear differences were observed between individuals with CD and controls in terms of risk of ED when other screening tests were used. More studies with larger samples and prospective designs are warranted to confirm these findings.

PMID: 28562523 [PubMed - indexed for MEDLINE]

Celiac Disease Symptom Resolution: Effectiveness of the Gluten-free Diet.

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Celiac Disease Symptom Resolution: Effectiveness of the Gluten-free Diet.

J Pediatr Gastroenterol Nutr. 2018 01;66(1):48-52

Authors: Sansotta N, Amirikian K, Guandalini S, Jericho H

Abstract
OBJECTIVE: The aim of the study was to evaluate the efficacy of the gluten-free diet (GFD) on gastrointestinal (GI) and extra-intestinal (EI) symptom resolution and identify predictors for persistence of symptoms in all celiac patients at the University of Chicago.
METHODS: We conducted a retrospective chart review from 2002 to 2015. GI symptoms included abdominal pain, bloating, constipation, diarrhea, failure to thrive/weight loss, nausea, reflux, and vomiting. EI symptoms included abnormal liver enzymes, arthralgia/arthritis, dermatitis herpetiformis, alopecia, fatigue, headache, anemia, stomatitis, myalgia, psychiatric disorders, rashes, seizures, neuropathy, short stature, delayed puberty, osteoporosis, and infertility.
RESULTS: A total of 554 patients (227 children) with celiac disease (CeD) were included. Abdominal pain, diarrhea and failure to thrive were the most common GI symptoms in children whereas diarrhea, bloating, and abdominal pain were most common in adults. Short stature, fatigue, and headache were the most common EI symptoms in children whereas iron deficiency anemia, fatigue, and headache/psychiatric disorders were most common in adults. Children had significantly higher rates of EI and GI symptom resolution as compared to adults, with greater rates of improvements in GI versus EI symptoms at more than 24 months. Long duration of symptoms, female sex, and non-adherence to a GFD were the most important significant predictors of failure to clinically improve.
CONCLUSIONS: On a strict GFD, children report greater rates of both GI and EI symptom resolution as compared to adults with greater rates of improvement in GI over EI symptoms. Early recognition of CeD and close attention to diet adherence may help in symptom resolution.

PMID: 28514243 [PubMed - indexed for MEDLINE]

Celiac Disease Autoimmunity.

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Celiac Disease Autoimmunity.

Arch Immunol Ther Exp (Warsz). 2018 Dec;66(6):423-430

Authors: López Casado MÁ, Lorite P, Ponce de León C, Palomeque T, Torres MI

Abstract
Celiac disease is an autoimmune condition triggered by the ingestion of gluten, the protein fraction of wheat, barley and rye. It is not simply an intestinal disease; it is multifactorial caused by many different genetic factors acting together with non-genetic causes. Similar to other autoimmune diseases, celiac disease is a polygenic disorder for which the major histocompatibility complex locus is the most important genetic factor, and is the result of an immune response to self-antigens leading to tissue destruction and the autoantibodies production. Celiac disease exemplifies how an illness can have autoimmune-like features having to be driven by exogenous antigen and how can be reasonably considered as a model of organ-specific autoimmunity.

PMID: 30167716 [PubMed - indexed for MEDLINE]

A new ELISA for autoantibodies to steroid 21-hydroxylase.

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A new ELISA for autoantibodies to steroid 21-hydroxylase.

Clin Chem Lab Med. 2018 05 24;56(6):933-938

Authors: Del Pilar Larosa M, Chen S, Steinmaus N, Macrae H, Guo L, Masiero S, Garelli S, Costa MD, Bossowski A, Furmaniak J, Betterle C, Smith BR

Abstract
BACKGROUND: A new ELISA for autoantibodies to steroid 21-hydroxylase (21-OH Ab) is described.
METHODS: In the assay test sample autoantibodies form a bridge between 21-OH coated onto the plate well and liquid phase 21-OH-biotin. Bound 21-OH-biotin is detected by the addition of streptavidin peroxidase and colorogenic peroxidase substrate.
RESULTS: Of 100 samples from patients with autoimmune Addison's disease, 86 (86%) were positive for 21-OH Ab ELISA whereas 84 (84%) were positive in an immunoprecipitation assay based on 125I-labeled 21-OH. Six (0.6%) of 928 healthy adult blood donors and 1 (2.0%) of 49 adult patients with type 1 diabetes mellitus (T1DM) were positive by ELISA. No samples from adult patients with Graves' disease (GD; n=50), celiac disease (n=29), systemic lupus erythematosis (n=9) or rheumatoid arthritis (n=20) were positive by ELISA. However, 2/51 (3.9%) children with GD, 3/69 (4.3%) children with Hashimoto's thyroiditis (HT) and 3/119 (2.5%) children with T1DM alone or associated with autoimmune thyroid disorders were ELISA positive.
CONCLUSIONS: The new assay should be useful for screening patients known to be at increased risk of developing clinical autoimmune Addison's disease, in particular children with HT, GD and/or T1DM.

PMID: 29267164 [PubMed - indexed for MEDLINE]

[Coeliac disease in children: a changing clinical spectrum].

[Coeliac disease in children: a changing clinical spectrum].

Ned Tijdschr Geneeskd. 2019 Mar 19;163:

Authors: van Kalleveen MW, de Meij T, Plötz FB

Abstract
Over the past decades the clinical spectrum of paediatric coeliac disease has profoundly changed, from a classical presentation with distended abdomen, diarrhoea and failure to thrive to more atypical symptoms. These days, children commonly present with symptoms such as recurrent abdominal pain, fatigue, iron deficiency anaemia and constipation. Age at diagnosis has also increased over the past few years. In the past 20 years the incidence of the disease in the Netherlands has increased from 12.3 to 21.1 per 100,000 inhabitants, reaching a stable level in the past 5 years. In approximately 10% of children, serological test results are negative on first examination but become positive after repeated testing in the years that follow, emphasising the need for alertness when first tests are negative and symptoms persist. We underscore the guidelines' advice to apply a low threshold in testing for coeliac disease in children with atypical symptoms.

PMID: 30945827 [PubMed - in process]

Potential use of MCR-ALS for the identification of coeliac-related biochemical changes in hyperspectral Raman maps from pediatric intestinal biopsies.

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Potential use of MCR-ALS for the identification of coeliac-related biochemical changes in hyperspectral Raman maps from pediatric intestinal biopsies.

Integr Biol (Camb). 2018 06 18;10(6):356-363

Authors: Fornasaro S, Vicario A, De Leo L, Bonifacio A, Not T, Sergo V

Abstract
Raman hyperspectral imaging is an emerging practice in biological and biomedical research for label free analysis of tissues and cells. Using this method, both spatial distribution and spectral information of analyzed samples can be obtained. The current study reports the first Raman microspectroscopic characterisation of colon tissues from patients with Coeliac Disease (CD). The aim was to assess if Raman imaging coupled with hyperspectral multivariate image analysis is capable of detecting the alterations in the biochemical composition of intestinal tissues associated with CD. The analytical approach was based on a multi-step methodology: duodenal biopsies from healthy and coeliac patients were measured and processed with Multivariate Curve Resolution Alternating Least Squares (MCR-ALS). Based on the distribution maps and the pure spectra of the image constituents obtained from MCR-ALS, interesting biochemical differences between healthy and coeliac patients has been derived. Noticeably, a reduced distribution of complex lipids in the pericryptic space, and a different distribution and abundance of proteins rich in beta-sheet structures was found in CD patients. The output of the MCR-ALS analysis was then used as a starting point for two clustering algorithms (k-means clustering and hierarchical clustering methods). Both methods converged with similar results providing precise segmentation over multiple Raman images of studied tissues.

PMID: 29756143 [PubMed - indexed for MEDLINE]

Epitope Selection for HLA-DQ2 Presentation: Implications for Celiac Disease and Viral Defense.

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Epitope Selection for HLA-DQ2 Presentation: Implications for Celiac Disease and Viral Defense.

J Immunol. 2019 Mar 29;:

Authors: Hung SC, Hou T, Jiang W, Wang N, Qiao SW, Chow IT, Liu X, van der Burg SH, Koelle DM, Kwok WW, Sollid LM, Mellins ED

Abstract
We have reported that the major histocompatibility molecule HLA-DQ2 (DQA1*05:01/DQB1*02:01) (DQ2) is relatively resistant to HLA-DM (DM), a peptide exchange catalyst for MHC class II. In this study, we analyzed the role of DQ2/DM interaction in the generation of DQ2-restricted gliadin epitopes, relevant to celiac disease, or DQ2-restricted viral epitopes, relevant to host defense. We used paired human APC, differing in DM expression (DMnull versus DMhigh) or differing by expression of wild-type DQ2, versus a DM-susceptible, DQ2 point mutant DQ2α+53G. The APC pairs were compared for their ability to stimulate human CD4+ T cell clones. Despite higher DQ2 levels, DMhigh APC attenuated T cell responses compared with DMnull APC after intracellular generation of four tested gliadin epitopes. DMhigh APC expressing the DQ2α+53G mutant further suppressed these gliadin-mediated responses. The gliadin epitopes were found to have moderate affinity for DQ2, and even lower affinity for the DQ2 mutant, consistent with DM suppression of their presentation. In contrast, DMhigh APC significantly promoted the presentation of DQ2-restricted epitopes derived intracellularly from inactivated HSV type 2, influenza hemagglutinin, and human papillomavirus E7 protein. When extracellular peptide epitopes were used as Ag, the DQ2 surface levels and peptide affinity were the major regulators of T cell responses. The differential effect of DM on stimulation of the two groups of T cell clones implies differences in DQ2 presentation pathways associated with nonpathogen- and pathogen-derived Ags in vivo.

PMID: 30926644 [PubMed - as supplied by publisher]

Risk of bacterial pneumonia and pneumococcal infection in youths with celiac disease - A population-based study.

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Risk of bacterial pneumonia and pneumococcal infection in youths with celiac disease - A population-based study.

Dig Liver Dis. 2019 Feb 28;:

Authors: Canova C, Ludvigsson J, Baldo V, Barbiellini Amidei C, Zanier L, Zingone F

Abstract
OBJECTIVE: Assess the risk of hospitalizations for bacterial pneumonia or pneumococcal infections, in a cohort of young individuals with celiac disease (CD) compared to matched references.
STUDY DESIGN: The cohort consists of 213,635 individuals, born in 1989-2012 and resident in Friuli-Venezia Giulia (Italy). Through pathology reports, hospital discharge records or co-payment exemptions, we identified 1294 CD patients and 6470 reference individuals matched by gender and birth year. We considered hospital admissions for first episodes of bacterial pneumonia and pneumococcal infections. Hazard ratios (HRs) for episodes after CD diagnosis were calculated with Cox regression and odds ratios (OR) for the ones before CD diagnosis with conditional logistic regression. Further analyses were performed on unvaccinated follow-up periods.
RESULTS: 14 CD patients (in 9450 person-years) and 42 references (in 48,335 person-years) experienced a first episode of bacterial pneumonia, with an increased risk among CD patients (HR 1.82; 95%CI 0.98-3.35). Risks of bacterial pneumonia were significantly increased before CD diagnosis and especially the year before CD diagnosis (OR 6.00, 95%CI 1.83-19.66). Risks of pneumococcal infections showed a non-significant increase in CD patients.
CONCLUSIONS: CD children and youth showed an increased risk of bacterial pneumonia, especially in proximity to CD diagnosis. Anti-pneumococcal vaccination should be recommended to all young CD patients.

PMID: 30926284 [PubMed - as supplied by publisher]

Structural variation in the gut microbiome associates with host health.

Structural variation in the gut microbiome associates with host health.

Nature. 2019 Mar 27;:

Authors: Zeevi D, Korem T, Godneva A, Bar N, Kurilshikov A, Lotan-Pompan M, Weinberger A, Fu J, Wijmenga C, Zhernakova A, Segal E

Abstract
Differences in the presence of even a few genes between otherwise identical bacterial strains may result in critical phenotypic differences. Here we systematically identify microbial genomic structural variants (SVs) and find them to be prevalent in the human gut microbiome across phyla and to replicate in different cohorts. SVs are enriched for CRISPR-associated and antibiotic-producing functions and depleted from housekeeping genes, suggesting that they have a role in microbial adaptation. We find multiple associations between SVs and host disease risk factors, many of which replicate in an independent cohort. Exploring genes that are clustered in the same SV, we uncover several possible mechanistic links between the microbiome and its host, including a region in Anaerostipes hadrus that encodes a composite inositol catabolism-butyrate biosynthesis pathway, the presence of which is associated with lower host metabolic disease risk. Overall, our results uncover a nascent layer of variability in the microbiome that is associated with microbial adaptation and host health.

PMID: 30918406 [PubMed - as supplied by publisher]

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