Recent PubMed Articles on Coeliac Disease (External)

Author Correction: Individual variations in cardiovascular-disease-related protein levels are driven by genetics and gut microbiome.

Author Correction: Individual variations in cardiovascular-disease-related protein levels are driven by genetics and gut microbiome.

Nat Genet. 2018 Oct 19;:

Authors: Zhernakova DV, Le TH, Kurilshikov A, Atanasovska B, Bonder MJ, Sanna S, Claringbould A, Võsa U, Deelen P, Franke L, de Boer RA, Kuipers F, Netea MG, Hofker MH, Wijmenga C, Zhernakova A, Fu J, LifeLines cohort study, BIOS consortium

Abstract
In the version of this paper originally published, there was a typographical error. In the Discussion, the sentence "In line with this, Ep-CAM-deficient mice exhibited increased intestinal permeability and decreased ion transport60, which may contribute to CVD susceptibility risk59" originally read iron instead of ion transport. This error has been corrected in the HTML, PDF and print versions of the article.

PMID: 30341443 [PubMed - as supplied by publisher]

Screening for coeliac disease in 1624 mainly asymptomatic children with type 1 diabetes: is genotyping for coeliac-specific human leucocyte antigen the right approach?

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Screening for coeliac disease in 1624 mainly asymptomatic children with type 1 diabetes: is genotyping for coeliac-specific human leucocyte antigen the right approach?

Arch Dis Child. 2018 Oct 16;:

Authors: Binder E, Rohrer T, Denzer C, Marg W, Ohlenschläger U, Schenk-Huber H, Schierloh U, Skopnik H, Fröhlich-Reiterer EE, Holl RW, Prinz N

Abstract
OBJECTIVES: To investigate the frequency of coeliac disease (CD)-specific human leucocyte antigen (HLA) genotypes in paediatric patients with type 1 diabetes (T1D), who are known to have a higher prevalence of CD than the general population, and to evaluate whether HLA genotyping is a suitable first-line screening method for CD.
STUDY DESIGN: The study was a multicentre observational analysis of patients with T1D aged <20 years of whom a subgroup had undergone HLA genotyping. Patient data were retrieved from the Diabetes Prospective Follow-up database, a large diabetes follow-up registry. The present analysis included data from 439 centres throughout Germany, Austria, Switzerland and Luxembourg.
RESULTS: In March 2017, the database contained 75 202 patients with T1D (53% male, mean age (SD) 14.6 (4.1) years, mean age at diagnosis 8.8 (4.3) years and mean diabetes duration 5.8 (4.3) years). 1624 patients had undergone coeliac-specific HLA genotyping, of whom 1344 (82.8%) were positive for HLA-DQ2, HLA-DQ8 or both, while 17.2% had no coeliac-specific HLA-markers. 26.6% of at-risk patients had a clinical suspected diagnosis of CD, and 3.6% had biopsy-proven CD.
CONCLUSIONS: Genotyping for HLA-DQ2, HLA-DQ8 or both is positive in the vast majority (>80%) of patients with T1D. Therefore, screening for coeliac-specific HLA genotypes as a first-line test is not a suitable method to exclude CD in T1D. Regular screening for coeliac-specific antibodies in T1D is still recommended.

PMID: 30327331 [PubMed - as supplied by publisher]

Genetic correlations among psychiatric and immune-related phenotypes based on genome-wide association data.

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Genetic correlations among psychiatric and immune-related phenotypes based on genome-wide association data.

Am J Med Genet B Neuropsychiatr Genet. 2018 Oct 16;:

Authors: Tylee DS, Sun J, Hess JL, Tahir MA, Sharma E, Malik R, Worrall BB, Levine AJ, Martinson JJ, Nejentsev S, Speed D, Fischer A, Mick E, Walker BR, Crawford A, Grant SFA, Polychronakos C, Bradfield JP, Sleiman PMA, Hakonarson H, Ellinghaus E, Elder JT, Tsoi LC, Trembath RC, Barker JN, Franke A, Dehghan A, 23 and Me Research Team, Inflammation Working Group of the CHARGE Consortium, METASTROKE Consortium of the International Stroke Genetics Consortium, Netherlands Twin Registry, neuroCHARGE Working Group, Obsessive Compulsive and Tourette Syndrome Working Group of the Psychiatric Genomics Consortium, Faraone SV, Glatt SJ

Abstract
Individuals with psychiatric disorders have elevated rates of autoimmune comorbidity and altered immune signaling. It is unclear whether these altered immunological states have a shared genetic basis with those psychiatric disorders. The present study sought to use existing summary-level data from previous genome-wide association studies to determine if commonly varying single nucleotide polymorphisms are shared between psychiatric and immune-related phenotypes. We estimated heritability and examined pair-wise genetic correlations using the linkage disequilibrium score regression (LDSC) and heritability estimation from summary statistics methods. Using LDSC, we observed significant genetic correlations between immune-related disorders and several psychiatric disorders, including anorexia nervosa, attention deficit-hyperactivity disorder, bipolar disorder, major depression, obsessive compulsive disorder, schizophrenia, smoking behavior, and Tourette syndrome. Loci significantly mediating genetic correlations were identified for schizophrenia when analytically paired with Crohn's disease, primary biliary cirrhosis, systemic lupus erythematosus, and ulcerative colitis. We report significantly correlated loci and highlight those containing genome-wide associations and candidate genes for respective disorders. We also used the LDSC method to characterize genetic correlations among the immune-related phenotypes. We discuss our findings in the context of relevant genetic and epidemiological literature, as well as the limitations and caveats of the study.

PMID: 30325587 [PubMed - as supplied by publisher]

Gluten and Functional Abdominal Pain Disorders in Children.

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Gluten and Functional Abdominal Pain Disorders in Children.

Nutrients. 2018 Oct 12;10(10):

Authors: Llanos-Chea A, Fasano A

Abstract
In children, functional gastrointestinal disorders (FGIDs) are common at all ages. Consumption of certain foods, particularly gluten, is frequently associated with the development and persistence of FGIDs and functional abdominal pain disorders (FAPDs) in adults and children. However, this association is not well defined. Even without a diagnosis of celiac disease (CD), some people avoid gluten or wheat in their diet since it has been shown to trigger mostly gastrointestinal symptoms in certain individuals, especially in children. The incidence of conditions such as non-celiac gluten sensitivity (NCGS) is increasing, particularly in children. On the other hand, CD is a chronic, autoimmune small intestinal enteropathy with symptoms that can sometimes be mimicked by FAPD. It is still unclear if pediatric patients with irritable bowel syndrome (IBS) are more likely to have CD. Abdominal, pain-associated FGID in children with CD does not seem to improve on a gluten-free diet. The threshold for gluten tolerance in patients with NCGS is unknown and varies among subjects. Thus, it is challenging to clearly distinguish between gluten exclusion and improvement of symptoms related solely to functional disorders.

PMID: 30322070 [PubMed - in process]

Extra-Intestinal Manifestation of Celiac Disease in Children.

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Extra-Intestinal Manifestation of Celiac Disease in Children.

Nutrients. 2018 Jun 12;10(6):

Authors: Jericho H, Guandalini S

Abstract
The aim of this literature review is to discuss the extra-intestinal manifestations of celiac disease within the pediatric celiac population.

PMID: 29895731 [PubMed - indexed for MEDLINE]

Prevalence and Clinical Features of Celiac Disease in Healthy School-Aged Children.

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Prevalence and Clinical Features of Celiac Disease in Healthy School-Aged Children.

Dig Dis Sci. 2018 Oct 12;:

Authors: Beser OF, Gulluelli E, Cullu Cokugras F, Erkan T, Kutlu T, Yagci RV, Erbek Alp F, Ercal G, Kepil N, Kucur M, Northern Cyprus Celiac Study Group

Abstract
BACKGROUND/AIMS: The aim of this study was to determine the prevalence of celiac disease (CD) in healthy school-aged children in the northern region of Cyprus and to investigate the existence of potential markers that may accompany CD. This is the first study to measure the prevalence of CD in the northern region of Cyprus.
METHODS: This study included 3792 school-aged children who were between the ages of 6 and 10 years between January 2015 and October 2016. CD was screened using total serum IgA, IgA anti-tissue transglutaminase (tTG), and IgA antiendomysial (EMA) antibodies. Subjects with selective IgA deficiency were further tested for IgG-tTG. Small intestinal biopsies were performed on all subjects with tTG antibody positivity. Risk factors and symptoms related to CD were evaluated using questionnaires in both the CD and control groups.
RESULTS: Of the 3792 subjects, 39 were antibody positive (IgA-tTG was positive only in 14 subjects, IgA-tTG plus IgA-EMA in 21 subjects, and IgG-tTG in 4 subjects). IgA deficiency was detected in 11 subjects (0.29%). IgG-tTG was positive in 4 subjects with IgA deficiency (36.3%). Intestinal biopsies were performed on 28 of the 39 seropositive subjects. The biopsy findings of 15 children were consistent with CD (IgA-tTG positive in 3, IgA-tTG and IgA-EMA positive in 10, and IgG-tTG positive in 2). Thus, biopsies confirmed CD in 1:256 children (0.39%).
CONCLUSIONS: Our study, which is the first study of school-aged children from the northern region of Cyprus, revealed that CD is a prevalent disease in this region.

PMID: 30311156 [PubMed - as supplied by publisher]

The association of Inflammatory Bowel diseases with autoimmune disorders: a population-based report from the epi-IIRN.

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The association of Inflammatory Bowel diseases with autoimmune disorders: a population-based report from the epi-IIRN.

J Crohns Colitis. 2018 Oct 09;:

Authors: Bar Yehuda S, Axlerod R, Toker O, Zigman N, Goren I, Mourad V, Lederman N, Cohen N, Matz E, Dushnitzky D, Gavish M, Borovsky N, Schwarts D, Dotan I, Turner D

Abstract
Introduction: There are conflicting data on the association between inflammatory bowel diseases (IBD) and autoimmunity disorders. The aim of this study was to explore this association including the effect of medications on this association.
Methods: We utilized health administrative data collected by 3 of 4 Israel's Health Maintenance Organizations (HMO) covering 52% of the population of Israel. We explored the prevalence of the following autoimmune disorders: Insulin Dependent Diabetes Mellitus (IDDM), psoriasis, Sjögren syndrome, celiac, systemic lupus erythematosus (SLE), primary sclerosis cholangitis (PSC) and autoimmune thyroiditis, among all IBD patients versus non-IBD controls. Case ascertainment was determined according to validated computerized algorithms.
Results: 12,625 IBD patients were compared to 12,625 controls. A total of 1,395 (11.1%) IBD patients had at least one autoimmune disease compared with 740 (5.9%) of non-IBD controls (OR 95%CI=1.99 (1.81-2.19); P<0.05); all autoimmune diseases, except for thyroiditis, were more prevalent among IBD patients. Adjusted for confounding variables, anti-TNF medications were associated with a higher prevalence of psoriasis (54 (5.7%) in IBD vs 177 (4.1%) in controls; OR 95%CI=1.50 (1.07-2.08); P<0.05) but lower prevalence of Sjögren (1 (0.1%) vs. 39 (0.9%); OR 95%CI=0.13 (0.02-0.94); P<0.05) and celiac disease (11 (1.2%) vs. 68 (1.6%); OR 95%CI=0.51 (0.27-0.99); P<0.05). Thiopurines and 5ASA were not associated with any autoimmune disorder.
Conclusion: IBD is associated with all autoimmune diseases explored here except for thyroiditis. Anti-TNF users have a higher prevalence of psoriasis, and lower prevalence of Sjögren and celiac disease.

PMID: 30304371 [PubMed - as supplied by publisher]

Headache Associated with Coeliac Disease: A Systematic Review and Meta-Analysis.

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Headache Associated with Coeliac Disease: A Systematic Review and Meta-Analysis.

Nutrients. 2018 Oct 06;10(10):

Authors: Zis P, Julian T, Hadjivassiliou M

Abstract
OBJECTIVE: The aim of this systematic review was to explore the relationship between coeliac disease (CD) and headache. The objectives were to establish the prevalence of each entity amongst the other, to explore the role of gluten free diet (GFD), and to describe the imaging findings in those affected by headaches associated with CD.
METHODOLOGY: A systematic computer-based literature search was conducted on the PubMed database. Information regarding study type, population size, the age group included, prevalence of CD amongst those with headache and vice versa, imaging results, the nature of headache, and response to GFD.
RESULTS: In total, 40 articles published between 1987 and 2017 qualified for inclusion in this review. The mean pooled prevalence of headache amongst those with CD was 26% (95% CI 19.5⁻33.9%) in adult populations and 18.3% (95% CI 10.4⁻30.2%) in paediatric populations. The headaches are most often migraine-like. In children with idiopathic headache, the prevalence of CD is 2.4% (95% CI 1.5⁻3.7%), whereas data for adult populations is presently unavailable. Brain imaging can be normal, although, cerebral calcifications on CT, white matter abnormalities on MRI and deranged regional cerebral blood flow on SPECT can be present. GFD appears to be an effective management for headache in the context of CD, leading to total resolution of headaches in up to 75% of patients.
CONCLUSIONS: There is an increased prevalence of CD amongst idiopathic headache and vice versa. Therefore, patients with headache of unknown origin should be screened for CD, as such patients may symptomatically benefit from a GFD.

PMID: 30301194 [PubMed - in process]

Oxidative and Antioxidative Status of Children with Celiac Disease Treated with a Gluten Free-Diet.

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Oxidative and Antioxidative Status of Children with Celiac Disease Treated with a Gluten Free-Diet.

Oxid Med Cell Longev. 2018;2018:1324820

Authors: Rowicka G, Czaja-Bulsa G, Chełchowska M, Riahi A, Strucińska M, Weker H, Ambroszkiewicz J

Abstract
Aims: Oxidative stress is a factor involved in the pathogenesis of celiac disease (CD), possibly affecting the course of the disease and celiac-related complications. We assessed the intensity of oxidative processes and the efficiency of antioxidant defense in children with celiac disease. Methods. Group I (n = 32) consisted of children with CD treated with a gluten-free diet, and group II (n = 24) consisted of healthy children on a traditional diet. Antioxidative and oxidative status was assessed by measurement of serum total antioxidant capacity (TAC), total oxidant capacity (TOC), and oxidized low-density lipoprotein (ox-LDL) and on the basis of oxidative stress index (OSI).
Results: There were no significant differences in serum TAC, TOC, ox-LDL, and OSI between children with CD and healthy children. Cluster analysis showed that the group of children with CD is not homogeneous in terms of serum TAC and TOC levels. About 50% of these children had TAC levels < 1.3 mmol/L and TOC levels > 0.35 mmol/L.
Conclusions: Strict adherence to a gluten-free diet by children with CD seems to be important for maintaining oxidative-antioxidant balance. However, further research is needed to identify factors potentially responsible for increased oxidative stress in some children with celiac disease despite adherence to a gluten-free diet.

PMID: 29854070 [PubMed - indexed for MEDLINE]

Characterization of globulin storage proteins of a low prolamin cereal species in relation to celiac disease.

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Characterization of globulin storage proteins of a low prolamin cereal species in relation to celiac disease.

Sci Rep. 2017 01 04;7:39876

Authors: Gell G, Kovács K, Veres G, Korponay-Szabó IR, Juhász A

Abstract
Brachypodium distachyon, a small annual grass with seed storage globulins as primary protein reserves was used in our study to analyse the toxic nature of non-prolamin seed storage proteins related to celiac disease. The main storage proteins of B. distachyon are the 7S globulin type proteins and the 11S, 12S seed storage globulins similar to oat and rice. Immunoblot analyses using serum samples from celiac disease patients were carried out followed by the identification of immune-responsive proteins using mass spectrometry. Serum samples from celiac patients on a gluten-free diet, from patients with Crohn's disease and healthy subjects, were used as controls. The identified proteins with intense serum-IgA reactivity belong to the 7S and 11-12S seed globulin family. Structure prediction and epitope predictions analyses confirmed the presence of celiac disease-related linear B cell epitope homologs and the presence of peptide regions with strong HLA-DQ8 and DQ2 binding capabilities. These results highlight that both MHC-II presentation and B cell response may be developed not only to prolamins but also to seed storage globulins. This is the first study of the non-prolamin type seed storage proteins of Brachypodium from the aspect of the celiac disease.

PMID: 28051174 [PubMed - indexed for MEDLINE]

Non-celiac gluten/wheat sensitivity (NCGS)-a currently undefined disorder without validated diagnostic criteria and of unknown prevalence: Position statement of the task force on food allergy of the German Society of Allergology and Clinical Immunology...

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Non-celiac gluten/wheat sensitivity (NCGS)-a currently undefined disorder without validated diagnostic criteria and of unknown prevalence: Position statement of the task force on food allergy of the German Society of Allergology and Clinical Immunology (DGAKI).

Allergo J Int. 2018;27(5):147-151

Authors: Reese I, Schäfer C, Kleine-Tebbe J, Ahrens B, Bachmann O, Ballmer-Weber B, Beyer K, Bischoff SC, Blümchen K, Dölle S, Enck P, Enninger A, Huttegger I, Lämmel S, Lange L, Lepp U, Mahler V, Mönnikes H, Ockenga J, Otto B, Schnadt S, Szepfalusi Z, Treudler R, Wassmann-Otto A, Zuberbier T, Werfel T, Worm M

Abstract
Within the last decade, non-celiac gluten/wheat sensitivity (NCGS) has been increasingly discussed not only in the media but also among medical specialties. The existence and the possible triggers of NCGS are controversial. Three international expert meetings which proposed recommendations for NCGS were not independently organized and only partially transparent regarding potential conflicts of interest of the participants. The present position statement reflects the following aspects about NCGS from an allergist's and nutritionist's point of view: (A) Validated diagnostic criteria and/or reliable biomarkers are still required. Currently, this condition is frequently self-diagnosed, of unknown prevalence and non-validated etiology. (B) Gluten has not been reliably identified as an elicitor of NCGS because of high nocebo and placebo effects. Double-blind, placebo-controlled provocation tests are of limited value for the diagnosis of NCGS and should be performed in a modified manner (changed relation of placebo and active substance). (C) Several confounders hamper the assessment of subjective symptoms during gluten-reduced or gluten-free diets. Depending on the selection of food items, e.g., an increased vegetable intake with soluble fibers, diets may induce physiological digestive effects and can modify gastrointestinal transit times independent from the avoidance of gluten. (D) A gluten-free diet is mandatory in celiac disease based on scientific evidence. However, a medically unjustified avoidance of gluten may bear potential disadvantages and risks. (E) Due to a lack of diagnostic criteria, a thorough differential diagnostic work-up is recommended when NCGS is suspected. This includes a careful patient history together with a food-intake and symptom diary, if necessary an allergy diagnostic workup and a reliable exclusion of celiac disease. We recommend such a structured procedure since a medically proven diagnosis is required before considering the avoidance of gluten.

PMID: 30294520 [PubMed]

Adherence to Gluten-Free Diet in Children with Celiac Disease.

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Adherence to Gluten-Free Diet in Children with Celiac Disease.

Nutrients. 2018 Oct 04;10(10):

Authors: Czaja-Bulsa G, Bulsa M

Abstract
Celiac disease (CD) can only be treated by rigorous life-long gluten-free diet (GFD). The study included 102 mothers and their CD children treated with GFD for at least two years. Frequency and cause of diet failure in children treated at present (54 children) and 10 years ago (48 children) were compared. Dietary adherence was evaluated serologically (tTG), while diet management difficulties were examined by means of a questionnaire. The study shows that one-third of patients fail to follow GFD, more often 10 years ago than now (40% vs. 26%; p < 0.05), mainly children aged 13⁻18 (54% vs. 40% now; p < 0.05). Younger children (up to 12) are less likely to abandon the diet (27% vs. 8%; p < 0.05). In this age group non-intentional diet failure prevails, while teenagers interrupt their diet intentionally (45% vs. 33%; p = ns (small population of children in this groups)). Currently, the most common causes of teenage diet failure are the absence of symptoms after consuming a small amount of gluten and, even more often, troublesome diet administration. Previously, the absence of peer acceptance prevailed. With this study we found that: 1. In West Pomerania, every fourth CD child does not follow GFD. 2. For years, teenagers have failed to follow GFD due to the absence of symptoms after consuming small amounts of gluten. 3. The incidence of non-intentional failure to follow GFD has significantly decreased over years, which indicates better dietary care.

PMID: 30287732 [PubMed - in process]

Allergic Diseases and Immune-Mediated Food Disorders in Pediatric Acute-Onset Neuropsychiatric Syndrome.

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Allergic Diseases and Immune-Mediated Food Disorders in Pediatric Acute-Onset Neuropsychiatric Syndrome.

Pediatr Allergy Immunol Pulmonol. 2018 Sep 01;31(3):158-165

Authors: Rosa JS, Hernandez JD, Sherr JA, Smith BM, Brown KD, Farhadian B, Mahony T, McGhee SA, Lewis DB, Thienemann M, Frankovich JD

Abstract
Background: The prevalence and impact of allergic and immune-mediated food disorders in pediatric acute-onset neuropsychiatric syndrome (PANS) are mostly unknown. Objective: We sought to explore the prevalence of atopic dermatitis (AD), asthma, allergic rhinitis (AR), IgE-mediated food allergies (FAs), and other immune-mediated food disorders requiring food avoidance in patients with PANS. In addition, to further understand the extent of food restriction in this population, we investigated the empiric use of dietary measures to improve PANS symptoms. Methods: Pediatric patients in a PANS Clinic and Research Program were given surveys regarding their caregiver burdens, allergic and food-related medical history, and whether food elimination resulted in perception of improvement of PANS symptoms. A review of health records was conducted to confirm that all responses in the survey were concordant with documentation of each patient's medical chart. Results: Sixty-nine (ages 4-20 years) of 80 subjects who fulfilled PANS criteria completed the surveys. Thirteen (18.8%) had AD, 11 (15.9%) asthma, 33 (47.8%) AR, 11 (15.9%) FA, 1 (1.4%) eosinophilic gastrointestinal disorders, 1 (1.4%) food protein-induced enterocolitis syndrome, 3 (4.3%) milk protein-induced proctocolitis syndrome, and 3 (4.3%) celiac disease. Thirty subjects (43.5%) avoided foods due to PANS; elimination of gluten and dairy was most common and was associated with perceived improvement of PANS symptoms (by parents). This perceived improvement was not confirmed with objective data. Conclusions: The prevalence of allergic and immune-mediated food disorders in PANS is similar to the general population as reported in the literature, with the exception of AR that appears to be more prevalent in our PANS cohort. More research will be required to establish whether diet or allergies influence PANS symptoms.

PMID: 30283713 [PubMed]

Early fecal microbiota composition in children who later develop celiac disease and associated autoimmunity.

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Early fecal microbiota composition in children who later develop celiac disease and associated autoimmunity.

Scand J Gastroenterol. 2018 04;53(4):403-409

Authors: Rintala A, Riikonen I, Toivonen A, Pietilä S, Munukka E, Pursiheimo JP, Elo LL, Arikoski P, Luopajärvi K, Schwab U, Uusitupa M, Heinonen S, Savilahti E, Eerola E, Ilonen J

Abstract
OBJECTIVES: Several studies have reported that the intestinal microbiota composition of celiac disease (CD) patients differs from healthy individuals. The possible role of gut microbiota in the pathogenesis of the disease is, however, not known. Here, we aimed to assess the possible differences in early fecal microbiota composition between children that later developed CD and healthy controls matched for age, sex and HLA risk genotype.
MATERIALS AND METHODS: We used 16S rRNA gene sequencing to examine the fecal microbiota of 27 children with high genetic risk of developing CD. Nine of these children developed the disease by the age of 4 years. Stool samples were collected at the age of 9 and 12 months, before any of the children had developed CD. The fecal microbiota composition of children who later developed the disease was compared with the microbiota of the children who did not have CD or associated autoantibodies at the age of 4 years. Delivery mode, early nutrition, and use of antibiotics were taken into account in the analyses.
RESULTS: No statistically significant differences in the fecal microbiota composition were found between children who later developed CD (n = 9) and the control children without disease or associated autoantibodies (n = 18).
CONCLUSIONS: Based on our results, the fecal microbiota composition at the age of 9 and 12 months is not associated with the development of CD. Our results, however, do not exclude the possibility of duodenal microbiota changes or a later microbiota-related trigger for the disease.

PMID: 29504486 [PubMed - indexed for MEDLINE]

Serum brain-derived neurotrophic factor in children with coeliac disease.

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Serum brain-derived neurotrophic factor in children with coeliac disease.

Eur J Clin Invest. 2018 May;48(5):e12916

Authors: Margoni D, Michalakakou K, Angeli E, Pervanidou P, Kanaka-Gantenbein C, Chrousos G, Papassotiriou I, Roma E

Abstract
BACKGROUND: Brain-derived neurotrophic factor (BDNF) is a neurotrophin that has a protective role in the nervous system and is involved in neural plasticity. It is abundant in the central nervous system, but is also expressed in the gastrointestinal tract. Coeliac disease (CD), characterised by intestinal inflammation, has some comorbidity with neurologic and mental disorders. The aim of this study was to evaluate circulating BDNF concentrations in patients with CD at diagnosis or on a gluten-free diet (GFD) for longer than 1 year and in healthy controls (HC).
MATERIALS AND METHODS: Fifty newly diagnosed patients with CD (aged 8.6 ± 3.7 years, 64.0% females), thirty-nine patients on GFD for longer than 1 year (aged 10.4 ± 3.4 years, 71.8% females) and 36 HC (aged 8 ± 1.7 years, 33.3% females) were included in the study. Along with anthropometric evaluation and standard blood chemistry, serum BDNF levels were measured by a specific immunoenzymatic assay.
RESULTS: Patients at diagnosis and on GFD had significantly higher BDNF levels (26 110 ± 8204 and 28 860 ± 7992 pg/mL), respectively, than HC (19 630 ± 8093 pg/mL, P < .001 for both CD groups). Patients on GFD had significantly higher BDNF levels than those at diagnosis (P = .02).
CONCLUSIONS: Serum BDNF concentrations were higher in patients with CD than in HC, regardless of their status of gluten consumption. This could be attributed either to a potential protective response to the inflammation of the intestine or to chronic stress.

PMID: 29469186 [PubMed - indexed for MEDLINE]

Epitope-specific immunotherapy targeting CD4-positive T cells in coeliac disease: two randomised, double-blind, placebo-controlled phase 1 studies.

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Epitope-specific immunotherapy targeting CD4-positive T cells in coeliac disease: two randomised, double-blind, placebo-controlled phase 1 studies.

Lancet Gastroenterol Hepatol. 2017 07;2(7):479-493

Authors: Goel G, King T, Daveson AJ, Andrews JM, Krishnarajah J, Krause R, Brown GJE, Fogel R, Barish CF, Epstein R, Kinney TP, Miner PB, Tye-Din JA, Girardin A, Taavela J, Popp A, Sidney J, Mäki M, Goldstein KE, Griffin PH, Wang S, Dzuris JL, Williams LJ, Sette A, Xavier RJ, Sollid LM, Jabri B, Anderson RP

Abstract
BACKGROUND: A gluten-free diet is the only means to manage coeliac disease, a permanent immune intolerance to gluten. We developed a therapeutic vaccine, Nexvax2, designed to treat coeliac disease. Nexvax2 is an adjuvant-free mix of three peptides that include immunodominant epitopes for gluten-specific CD4-positive T cells. The vaccine is intended to engage and render gluten-specific CD4-positive T cells unresponsive to further antigenic stimulation. We assessed the safety and pharmacodynamics of the vaccine in patients with coeliac disease on a gluten-free diet.
METHODS: We did two randomised, double-blind, placebo-controlled, phase 1 studies at 12 community sites in Australia, New Zealand, and the USA, in HLA-DQ2·5-positive patients aged 18-70 years who had coeliac disease and were on a gluten-free diet. In the screening period for ascending dose cohorts, participants were randomly assigned (1:1) by central randomisation with a simple block method to a double-blind crossover, placebo-controlled oral gluten challenge. Participants with a negative interferon γ release assay to Nexvax2 peptides after the screening oral gluten challenge were discontinued before dosing. For the biopsy cohorts, the screening period included an endoscopy, and participants with duodenal histology who had a Marsh score of greater than 1 were discontinued before dosing. Participants were subsequently randomly assigned to either Nexvax2 or placebo in ascending dose cohorts (2:1) and in biopsy cohorts (1:1) by central randomisation with a simple block method. In the three-dose study, participants received either Nexvax2 60 μg, 90 μg, or 150 μg weekly, or placebo over 15 days; in a fourth biopsy cohort, patients received either Nexvax2 at the maximum tolerated dose (MTD) or placebo. In the 16-dose study, participants received Nexvax2 150 μg or 300 μg or placebo twice weekly over 53 days; in a third biopsy cohort, patients also received either Nexvax2 at the MTD or placebo. In the 4-week post-treatment period, ascending dose cohorts underwent a further double-blind crossover, placebo-controlled oral gluten challenge, which had a fixed sequence, and biopsy cohorts had a gastroscopy with duodenal biopsies and quantitative histology within 2 weeks without oral gluten challenge. Participants, investigators, and study staff were masked to the treatment assignment, except for the study pharmacist. The primary endpoint was the number and percentage of adverse events in the treatment period in an intention-to-treat analysis. Both trials were completed and closed before data analysis. Trials were registered with the Australian New Zealand Clinical Trials Registry, numbers ACTRN12612000355875 and ACTRN12613001331729.
FINDINGS: Participants were enrolled from Nov 28, 2012, to Aug 14, 2014, in the three-dose study, and from Aug 3, 2012, to Sept 10, 2013, in the 16-dose study. Overall, 62 (57%) of 108 participants were randomly assigned after oral gluten challenge and 20 (71%) of 28 participants were randomly assigned after endoscopy. In the three-dose study, nine participants were randomly allocated to Nexvax2 60 μg and three to placebo (first cohort), nine were allocated to Nexvax2 90 μg and four to placebo (second cohort), eight were allocated to Nexvax2 150 μg and four to placebo (third cohort), and three were allocated to Nexvax2 150 μg and three to placebo (biopsy cohort). In the 16-dose study, eight participants were randomly allocated to Nexvax2 150 μg and four to placebo (first cohort), ten were allocated to Nexvax2 300 μg and three to placebo (second cohort), and seven were allocated to Nexvax2 150 μg and seven to placebo (biopsy cohort). The MTD for Nexvax2 was 150 μg because of transient, acute gastrointestinal adverse events with onset 2-5 h after initial doses of the vaccine, similar to those caused by gluten ingestion. In the ascending dose cohorts in the three-dose study, six (55%) of 11 placebo recipients, five (56%) of nine who received Nexvax2 60 μg, seven (78%) of nine who received Nexvax2 90 μg, and five (63%) of eight who received Nexvax2 150 μg had at least one treatment-emergent adverse event, as did all three (100%) placebo recipients and one (33%) of three Nexvax2 150 μg recipients in the biopsy cohort. In the ascending dose cohorts of the 16-dose study, five (71%) of seven placebo-treated participants, six (75%) of eight who received Nexvax2 150 μg, and all ten (100%) who received Nexvax2 300 μg had at least one treatment-emergent adverse event, as did six (86%) of seven placebo recipients and five (71%) of seven Nexvax2 150 μg recipients in the biopsy cohort. Vomiting, nausea, and headache were the only treatment-emergent adverse events that occurred in at least 5% of participants in either study. Among participants given the MTD, eight gastrointestinal treatment-emergent adverse events occurred in four (50%) of eight participants in the third cohort and none (0%) of three participants in the biopsy cohort in the three-dose study, and five events occurred in five (63%) of eight participants in the first cohort and three events in two (29%) of seven participants in the biopsy cohort of the 16-dose study. Median villous height to crypt depth ratio in distal duodenal biopsies was not significantly different between those who received the vaccine at the MTD on either schedule and those who received placebo. Of the participants who completed the post-treatment oral gluten challenge per protocol, interferon γ release assay to Nexvax2 peptides was negative (responders to treatment) in two (22%) of nine placebo-treated participants in the three-dose study versus two (33%) of six who received Nexvax2 60 μg, five (63%) of eight who received Nexvax2 90 μg, and six (100%) of six who received Nexvax2 150 μg (p=0·007); in the 16-dose study, none (0%) of five placebo-treated participants had a negative assay versus six (75%) of eight who received Nexvax2 150 μg (p=0·021).
INTERPRETATION: The MTD of Nexvax2 was 150 μg for twice weekly intradermal administration over 8 weeks, which modified immune responsiveness to Nexvax2 peptides without deterioration in duodenal histology. The gastrointestinal symptoms that followed the first intradermal administration of the vaccine resembled those associated with oral gluten challenge. These findings support continued clinical development of this potential therapeutic vaccine for coeliac disease.
FUNDING: ImmusanT.

PMID: 28506538 [PubMed - indexed for MEDLINE]

Evaluation of screening for celiac disease in children with juvenile idiopathic arthritis.

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Evaluation of screening for celiac disease in children with juvenile idiopathic arthritis.

Acta Paediatr. 2018 Sep 28;:

Authors: Öman A, Hansson T, Carlsson M, Berntson L

Abstract
AIM: To study the prevalence of celiac disease (CD) in children with Juvenile Idiopathic Arthritis (JIA), by screening a population-based cohort of children with JIA using autoantibodies against tissue transglutaminase (anti-TG2).
METHODS: All children diagnosed with JIA in three Swedish counties, with disease onset between 2007 and 2014, were included prospectively. Serum levels of IgA anti-TG2 antibodies, IgG anti-TG2 antibodies, and total IgA were analyzed. Children with positive levels of IgA anti-TG2 antibodies and children with IgA deficiency in combination with positive levels of IgG anti-TG2 antibodies were referred to the pediatric gastroenterology unit for gastroscopy and small intestine biopsy.
RESULTS: 216 children were included and analysis of IgA and IgG anti-TG2 antibodies was performed in 213 children. Three children were diagnosed with CD prior to the diagnosis of JIA and three additional children were found through screening, resulting in a CD point prevalence of 2.8% (95% CI 0.6%-5.0%).
CONCLUSION: We found a point prevalence of CD close to previous described prevalence in the general population of Swedish children. Therefore general screening for CD in children with JIA is not supported by our data. However, this study shows that asymptomatic CD in children with JIA may be found by screening. This article is protected by copyright. All rights reserved.

PMID: 30265401 [PubMed - as supplied by publisher]

Prevalence of celiac disease among school-age children in Çorum, Turkey.

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Prevalence of celiac disease among school-age children in Çorum, Turkey.

Turk J Gastroenterol. 2018 Sep;29(5):595-600

Authors: Comba A, Eren NB, Demir E

Abstract
BACKGROUND/AIMS: Celiac disease (CD) is an autoimmune enteropathy that develops in individuals with genetic susceptibility as a result of a permanent sensitivity to gluten found in grains. The prevalence of CD in Turkey is between 0.3% and 1%. However, the prevalence of CD in Çorum, a city in middle Anatolia in Turkey, is unknown. The purpose of this study was to identify the prevalence of childhood CD in Çorum and to detect patients with silent and atypical CD.
MATERIALS AND METHODS: The sample size was calculated using a stratified sampling method, to provide the sample number that would best represent this population. Screenings were conducted using rapid tissue transglutaminase IgA test kits.
RESULTS: A total of 1730 students were included in the study; 877 (50.6%) were female. Of students in the city center, 301 (34%) were in primary school, 299 (34%) were in secondary school, and 283 (32%) were in high school. As for towns, 847 (49%) students from 92 schools were included in the study. Eight children had positive screening results; 4 (50%) were female, and the average age was 11.6±3.4 (9-17) years. According to the celiac serology results and endoscopic duodenum biopsies, all children with positive screening results were diagnosed with CD. The prevalence of CD was found to be 0.46% in schoolchildren.
CONCLUSION: Various studies in Turkey have reported a prevalence of CD between 0.6% and 0.9%, with 0.47% reported in a multicenter study. The present study identified CD prevalence as 0.46% (1 in 216) among children in Çorum, Turkey.

PMID: 30260783 [PubMed - in process]

Autism & Gluten: The Proof By Regression!

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Autism & Gluten: The Proof By Regression!

Pediatr Neurol Briefs. 2018 Sep 14;32:9

Authors: Rahmoune H, Boutrid N

Abstract
Investigators from different clinical and research centers from Paris, France studied the polymorphisms of the HLA class II loci in an autistic population. Through a case control design, they looked for the distribution of HLA class II alleles, genotypes and haplotypes in Autism Spectrum Disorders (ASD) patients meeting DSM-IV TR criteria versus healthy controls (HC).

PMID: 30258271 [PubMed]

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