High Risk For Celiac Disease Research Articles

Celiac disease in children and adolescents with Down syndrome: behavioural, adaptive and sleep profiles.

Individuals with Down syndrome (DS) exhibit higher risk for celiac disease (CD) than general population. Although literature suggests CD could be associated with behavioural problems in both paediatric and adult age, such association has been poorly explored in children and adolescents DS. Therefore, the current study aimed to investigate differences in emotional/behavioural difficulties, adaptive skills and sleep problems between children with DS with and without CD. Data were retrospectively collected from a database including data from 381 individuals with DS (3-18years). The final sample included 65 participants, 27 with co-occurring CD and 38 age, IQ, sex and body mass index-matched controls without CD. Emotional/behavioural difficulties, adaptive skills and sleep problems were assessed through parent report questionnaires. No group differences emerged in emotional/behavioural difficulties, whereas participants in the CD group showed better adaptive skills in the practical domain than control group. Weak differences emerged in sleep problems. Youth with DS and co-occurring CD do not exhibit more emotional and behavioural problems than youth with DS without co-occurring CD but exhibit better adaptive skills in the practical domain.

Pregnancy- and birth-related risk factors for the development of childhood celiac disease.

To evaluate whether pregnancy and birth-related factors are associated with celiac disease (CD) in a large, United States (US)-based mother-child cohort. We analysed data gathering from the Massachusetts General Hospital Maternal Child Cohort (MMCC) of children born between 1998 and 2016. Data included the mode of delivery, maternal pregnancy and their offspring characteristics. We searched for CD cases by using diagnosis billing codes. Cox proportional hazard regression models were created to identify variables associated with CD. We identified 44 539 mother-child pairs who had at least one encounter by 5 years old and identified 173 children (0.4%) with CD diagnosis; median age at the diagnosis was 6 years. Overall, the adjusted hazard ratio (aHR) of caesarean delivery for CD was 1.39 (95% CI: 0.99, 1.96, p= 0.06) when compared to children born vaginally. After stratifying for the presence of labour, children born by Caesarean delivery without labour had a higher risk of CD (aHR 1.56; 95%CI: 1.01, 2.41; p=0.046) while infants born by Caesarean delivery with labour did not (aHR 1.26; 95% CI: 0.83, 1.93; p=0.28). Being born by Caesarean delivery without labour may be associated with an increased risk for CD in the US children.

Prevalence of haplotype DQ2/DQ8 and celiac disease in children with type 1 diabetes

Type 1 diabetes (T1D) and celiac disease (CD) coexist very often. Identification of the human leukocyte antigen (HLA) DQ2/DQ8 can confirm the genetic predisposition to CD. Negative result of this test allows to exclude CD with a high probability. It was suggested that in individuals with higher risk of CD, including T1D patients, the implementation of genetic testing should reduce the number of patients requiring systematic immunological screening. The aim of this study was to analyze the prevalence of different haplotypes predisposing to CD in children and adolescents with previously diagnosed T1D. Material and methods: A retrospective analysis was performed on 166 T1D children (91 girls) in whom HLA DQ2/DQ8 alleles were tested. In 9.6% CD was also diagnosed. Results: In 12.7% both HLA DQ2/DQ8 were negative. In 87.3% patients HLA DQ2 and/or DQ8 was positive, including 27.7% patients with both haplotypes DQ2.5 and DQ8 positive. In all CD patients the disease predisposing alleles were positive, while none of the HLA DQ2/DQ8 negative children were diagnosed with CD. Conclusions: The prevalence of HLA DQ2.5 and the HLA DQ2.5 / HLA DQ8 configuration is higher in patients with T1D, and CD compared to children with T1D alone. The combination of HLA DQ2 and HLA DQ8 most significantly increases the risk of developing CD. The group of HLA DQ2/DQ8 negative patients with improbable CD diagnosis, is relatively small. Most of T1D patients HLA DQ2/DQ8 positive need further regular antibody assessment. In patients with T1D, who are at high risk of developing CD, genetic testing may be considered to select those who require further systematic serological evaluation. Due to its retrospective nature, the study was not registered in the database of clinical trials and the Clinical trial registration number is not available.

Could I-FABP Be an Early Marker of Celiac Disease in Children with Type 1 Diabetes? Retrospective Study from the Tertiary Reference Centre.

Patients with type 1 diabetes (T1D) are at higher risk of celiac disease (CD). Recently, intestinal fatty acid binding protein (I-FABP) has been shown to be a serological biomarker of impaired intestinal barrier in CD. Thus, the aim of this study was to verify whether I-FABP could be an early marker of CD in pediatric T1D patients. I-FABP was measured in sera of patients with T1D (n = 156), active CD (n = 38), T1D with active CD (T1D-CD, n= 51), and age-matched healthy children (n = 55). Additionally, I-FABP was determined in T1D patients with negative CD serology at least one year before CD diagnosis (T1D-CD-1, n = 22), in CD patients on a gluten-free diet (CD-GFD, n = 36), and T1D-CD patients on GFD (T1D-CD-GFD, n = 39). Sera were tested using immunoenzymatic assay. Significantly increased levels of I-FABP were found in the T1D, active CD, and T1D-CD groups (1153 ± 665, 1104 ± 916, and 1208 ± 878, respectively) in comparison to healthy with controls (485 ± 416, p < 0.05). GFD induced a significant decrease in I-FABP levels in CD and T1D-CD groups (510 ± 492 and 548 ± 439, respectively). Interestingly, in T1D-CD-1 and T1D, I-FABP levels were comparable (833 ± 369 vs. 1153 ± 665), and significantly increased in relation to healthy controls and T1D-CD values on GFD. The results indicate that the epithelial barrier is disrupted in T1D patients independently of CD development; therefore, I-FABP cannot serve as an early marker of CD in T1D patients. Although GFD can improve epithelial recovery, the question remains as to whether GFD could exert beneficial effects on the intestinal barrier in early stages of T1D.

Differential expression of predisposing HLA-DQ2.5 alleles in DR5/DR7 celiac disease patients affects the pathological immune response to gluten

The DR5-DQ7/DR7-DQ2 genotype is very frequent among patients affected by celiac disease (CD), in Europe. This genotype, associated to high risk of CD, carries the HLA-DQA1*05 and HLA-DQB1*02 predisposing alleles, in trans configuration. The alleles encode the DQ2.5 heterodimer responsible of gluten peptide presentation on the surface of antigen-presenting cells (APCs), and consequent pathogenic CD4+ T cell activation. We demonstrated that DR5/DR7 APCs induce an anti-gluten CD4+ T cell response, of comparable intensity to that observed with APCs carrying DR1/DR3 genotype, which risk alleles are in cis configuration. In addition, we showed that DR5/DR7 APCs from celiac patients stimulated an effector CD4+ T cell response higher with respect to that induced by DR5/DR7 APCs from healthy subjects. To explain these findings, we assessed the DQ2.5 RNA and protein quantity. We showed that the expression of DQA1*05 and DQB1*02 risk alleles is much higher than the expression of non-CD-associated alleles, in agreement with the previous results obtained with DR1/DR3 genotype. The differential expression of transcripts influences the quantity of DQα1*05 and DQβ1*02 chains and, as consequence, the cell surface density of DQ2.5 heterodimers. Moreover, both RNA and proteins, are more abundant in APCs from celiac patients than controls. Finally, to unravel the mechanism regulating the expression of predisposing DQA1*05 and DQB1*02 alleles, we quantified the new synthetized RNA and found that the differential expression is explained by their transcription rate. Our results confirmed that the strength of antigen-specific CD4+ T cell response is mainly determined by the amount of gluten in the diet and provided a new possible approach for a personalized diagnosis and for risk stratification.

Prevalence of celiac disease in Iranian patients with type 1 diabetes: Asystematic review and meta-analysis.

Patients with type 1 diabetes mellitus (T1DM) are at high risk for celiac disease (CD) due to the common genetic background and interaction between environmental and immunological factors. The purpose of this systematic review and meta-analysis was to estimate the prevalence of CDamong Iranian patients with type 1 diabetes. The search for articles was conducted using the following keywords: "celiac disease," "celiac," "coeliac disease," "diabetes," "Iran," and all other possible combinations of these terms. The following databases were searched from inception to June 2019: Scientific Information Database (SID), MagIran, Web of Science, PubMed, and Scopus. Meta-analysis was performed using the random-effects models, and the heterogeneity of results across the studies was assessed using the Cochran's Q test and quantified by the I2 statistic. Data analysis was performed by Stata version 14. A total of 14 papers were included in the meta-analysis, involving 2030 Iranian patients with T1DM. The pooled prevalence of CD in patients with T1DM was 5% (95% CI 3-7). The prevalence of CD in Tehran (4%; 95% CI 1-6) was lower than in other provinces of the country (6%; 95% CI 4-8). Meta-regression analysis showed that, with increasing sample size, the prevalence of CD was significantly reduced (p = 0.018).Given the adverse effects of CD, such as osteoporosis and malignancy (especially lymphoma), patients with T1DM must be screened for CD.

IL-10 gene promoter region polymorphisms and their association with celiac disease.

in celiac disease (CD), immune response activation results in local cytokine network impairment. Interleukin 10 (IL-10) is a key anti-inflammatory cytokine in the prevention of inflammatory conditions. to analyze the association of single nucleotide polymorphisms in the IL-10 gene promoter region with CD in a population of Misiones Province, Argentina. DNA from whole blood was extracted from 40 patients with CD and 80 controls and the IL-10 gene promoter region containing polymorphisms rs1800896A/G, rs1800871T/C and rs1800872A/C was amplified. Risk was established by calculating odds ratios (OR) and statistical significance was considered as p < 0.05. there were no significant differences in rs1800896 genotype distribution between celiac patients and controls. The frequency of the CC genotype for rs1800871T/C and rs1800872A/C was lower among celiac patients (35 % vs 65 %; p = 0.002). CD risk was associated with carriers of the more uncommon T allele of rs1800871T/C and the more uncommon A allele of rs1800872A/C, with a dominant model (OR = 2.79; 95 % CI: 1.27-6.09; p = 0.01). A risk effect was found for haplotype ATA (OR = 3.05; 95 % CI: 1.25-7.46; p = 0.01). carriers of the less common T allele of rs1800871T/C and the less common A allele of rs1800872A/C in the IL-10 gene promoter are at high risk of CD with a dominant model. There was no risk for rs1800896A/G. The ATA haplotype showed an association with CD development.

Celiac autoantibody positivity in relation to clinical characteristics in children with type 1 diabetes

Type 1 diabetes is an autoimmune disorder with a high risk of celiac disease (CD). This study aimed to determine the celiac autoantibody status and the clinical characteristics among children with type 1 diabetes and autoantibody positivity for CD compared to those without serological evidence of CD. In this cross-sectional study, 240 children with type 1 diabetes underwent serological screening CD. Blood glucose, glycated hemoglobin (HbA1c), hemoglobin, calcium, phosphorous, Vitamin D, alanine aminotransferase (ALT), alkaline phosphatase (ALP), aspartate aminotransferase (AST), and gamma-glutamyl transferase (GGT) were evaluated. The participants were screened for human anti-endomysial antibody and human anti-tissue transglutaminase antibody. Of the 240 children with type 1 diabetes, 66 children were antibody positive for either anti-endomysial or anti-tissue transglutaminase or both autoantibodies for CD. There were 36 (54.5%) female and 30 (45.5%) male children with the mean age of 15.5±2.1 years. The mean duration of diabetes was 6.8±3.8 years. Only 35 (14.6%) children were found to have serological evidence of CD. CD is associated with type 1 diabetes. Serological screening for CD autoantibody should be performed routinely in children with type 1 diabetes. There is discrepancy in screening CD with antibodies, so a prospective follow-up of this cohort is needed for endoscopic evaluation and histopathological examination of intestinal biopsy to confirm CD in this population. Anti-endomysial and anti-tissue transglutaminase autoantibodies should be included for screening CD among children with type 1 diabetes. Patients should undergo an endoscopy to confirm a diagnosis of CD.

Association of Gluten Intake During the First 5 Years of Life With Incidence of Celiac Disease Autoimmunity and Celiac Disease Among Children at Increased Risk

High gluten intake during childhood may confer risk of celiac disease. To investigate if the amount of gluten intake is associated with celiac disease autoimmunity and celiac disease in genetically at-risk children. The participants in The Environmental Determinants of Diabetes in the Young (TEDDY), a prospective observational birth cohort study designed to identify environmental triggers of type 1 diabetes and celiac disease, were followed up at 6 clinical centers in Finland, Germany, Sweden, and the United States. Between 2004 and 2010, 8676 newborns carrying HLA antigen genotypes associated with type 1 diabetes and celiac disease were enrolled. Screening for celiac disease with tissue transglutaminase autoantibodies was performed annually in 6757 children from the age of 2 years. Data on gluten intake were available in 6605 children (98%) by September 30, 2017. Gluten intake was estimated from 3-day food records collected at ages 6, 9, and 12 months and biannually thereafter until the age of 5 years. The primary outcome was celiac disease autoimmunity, defined as positive tissue transglutaminase autoantibodies found in 2 consecutive serum samples. The secondary outcome was celiac disease confirmed by intestinal biopsy or persistently high tissue transglutaminase autoantibody levels. Of the 6605 children (49% females; median follow-up: 9.0 years [interquartile range, 8.0-10.0 years]), 1216 (18%) developed celiac disease autoimmunity and 447 (7%) developed celiac disease. The incidence for both outcomes peaked at the age of 2 to 3 years. Daily gluten intake was associated with higher risk of celiac disease autoimmunity for every 1-g/d increase in gluten consumption (hazard ratio [HR], 1.30 [95% CI, 1.22-1.38]; absolute risk by the age of 3 years if the reference amount of gluten was consumed, 28.1%; absolute risk if gluten intake was 1-g/d higher than the reference amount, 34.2%; absolute risk difference, 6.1% [95% CI, 4.5%-7.7%]). Daily gluten intake was associated with higher risk of celiac disease for every 1-g/d increase in gluten consumption (HR, 1.50 [95% CI, 1.35-1.66]; absolute risk by age of 3 years if the reference amount of gluten was consumed, 20.7%; absolute risk if gluten intake was 1-g/d higher than the reference amount, 27.9%; absolute risk difference, 7.2% [95% CI, 6.1%-8.3%]). Higher gluten intake during the first 5 years of life was associated with increased risk of celiac disease autoimmunity and celiac disease among genetically predisposed children.

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

BackgroundWe examined the association between the maternal genotype for celiac disease‐associated variants and risk of neural tube defects (NTDs).MethodsWe 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.ResultsThere 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).ConclusionIf confirmed, our results suggest that the maternal variants related to celiac disease may be involved in the risk of NTDs.

Infant milk-feeding practices and diagnosed celiac disease and inflammatory bowel disease in offspring: a systematic review

During the Pregnancy and Birth to 24 Months Project, the USDA and US Department of Health and Human Services initiated an evidence review on diet and health in these populations. The aim of these systematic reviews was to examine the relationships of never versus ever feeding human milk, shorter versus longer durations of any and exclusive human milk feeding, and feeding a lower versus a higher intensity of human milk to mixed-fed infants with diagnosed celiac disease and inflammatory bowel disease (IBD). The Nutrition Evidence Systematic Review team (formerly called the Nutrition Evidence Library) conducted systematic reviews with external experts. We searched CINAHL, Cochrane, Embase, and PubMed for articles published January, 1980 to March, 2016, dual-screened the results using predetermined criteria, extracted data from and assessed risk of bias for each included study, qualitatively synthesized the evidence, developed conclusion statements, and graded the strength of the evidence. We included 9 celiac disease and 17 IBD articles. Limited case-control evidence suggests never versus ever being fed human milk is associated with higher risk of celiac disease, but concerns about reverse causality precluded a conclusion about the relationship of shorter versus longer durations of any human milk feeding with celiac disease. Evidence examining never versus ever feeding human milk and IBD was inconclusive, and limited, but consistent, case-control evidence suggests that, among infants fed human milk, shorter versus longer durations of any human milk feeding are associated with higher risk of IBD. For both outcomes, evidence examining the duration of exclusive human milk feeding was scant and no articles examined the intensity of human milk fed to mixed-fed infants. Limited case-control evidence suggests that feeding human milk for short durations or not at all associates with higher risk of diagnosed IBD and celiac disease, respectively. The small number of studies and concern about reverse causality and recall bias prevent stronger conclusions.

Sex Difference in Celiac Disease in Undiagnosed Populations: A Systematic Review and Meta-analysis

A higher proportion of female vs male patients receive a diagnosis of celiac disease. Little isknown about sex-based differences in the prevalence of celiac disease in undiagnosed populations. We aimed to address this knowledge gap with a systematic review and meta-analysis. We searched MEDLINE, Embase, Cochrane, and Scopus databases through 2017 for studies of screen-detected or undiagnosed celiac disease. Our final analysis included studies that included screening and confirmatory tests (either second serologic analysis or a small intestine biopsy) and provided information on the sex of participants. Studies were excluded if they were performed with specific, high-risk, or referral populations. The primary outcome was the percentage of undetected celiac disease among female and male patients. We identified 4070 articles and analyzed data from 87. Our meta-analysis comprised data from 291,969 study participants. The pooled prevalence of undetected celiac disease in female participants was 0.589% (95% CI, 0.549%-0.629%) and in male participants was 0.415% (95% CI, 0.343%-0.487%). The risk of undetected celiac disease was higher among female than male participants (relative risk [RR], 1.42; 95% CI, 1.27-1.57; P < .00001). The I2 was 5% (low heterogeneity among studies). In subgroup analyses, the RR of celiac disease for girls vs boys was 1.79 (95% CI, 1.44-2.22; P < .00001; I2= 18%), the RR for female vs male blood donors was 1.13 (95% CI, 0.76-1.69; P= .54; I2= 0), and the RR for women vs men with villous atrophy was 1.38 (95% CI, 1.07-1.79; P= .01; I2= 0). In a systematic review and meta-analysis, we found a higher risk for celiac disease in women than men in an undiagnosed populations (identified through general population screening). The increased risk for celiac disease among girls and women should be considered for screening, diagnosis, and management strategies.

PMD52 - YIELD AND COSTS OF POINT-OF-CARE SCREENING TEST VERSUS CASE FINDING TO DIAGNOSE CELIAC DISEASE IN PEDIATRIC PATIENTS

Celiac Disease (CD) is an immune-mediated systemic disorder, common worldwide, caused by the ingestion of gluten in genetically-predisposed people. Low awareness of CD often leads to delays in diagnosis, which adds to medical costs because unrecognized CD is associated with excessive consumption of healthcare services and on-demand medications. This study has assessed the diagnostic yield and cost consequences of 2 strategies of pediatric CD in primary care: screening regardless of symptoms using a point-of-care test (POCT) for the detection versus case finding (CF). Children who went to their family pediatrician were offered POCT for anti-transglutaminase immunoglobulin A antibodies. Immediately after the test, but before knowing the results, a systematic search for one or more symptoms or conditions associated with higher risk for CD was performed. All POCT-positive subjects and those who were symptomatic at CF were referred to the CD Centers for disease confirmation. The costs of examinations and diagnostic and laboratory tests were estimated with regional outpatient tariffs (Sicily), and a price of €2.50 was used for each POCT. Two sensitivity analyses were performed, using ±20% of POCT price and a pediatrician visit cost of €15.31. POCT was offered to 3,358 children. This screening detected 16 new cases of CD; CF detected 5 new cases of CD, but all of these had positive POCT. In the base case, total costs and mean cost per CD patient detected were €10,932.83 and €683.30 for screening strategy with POCT, and €3,953.90 and €790.78 for CF, respectively. In both sensitivity analyses, POCT was less costly than CF. The results of our study suggest that mass screening may bridge the diagnostic gap for CD in children. The analysis has shown that POCT is more effective and less costly, for CD patient identified, than CF strategy.

Frequency of Celiac Disease in Children with Peptic Ulcers.

The aim of the present study is to investigate the frequency of celiac disease in children with peptic ulcers and to compare it with that of non-celiac peptic ulcers in terms of clinical and laboratory values. Upper gastrointestinal endoscopy was performed in 1769 patients at the Department of Pediatric Gastroenterology, The Faculty of Medicine, Cukurova University, Turkey, between January 2012 and January 2017. These cases consisted of subjects presenting with various GIS symptoms and indicated for endoscopy (with chronic diarrhea, delayed growth and development, abdominal pains, GIS bleeding, etc.). The levels of immunoglobulin A (IgA) serum anti-tissue transglutaminase antibodies, IgA anti-endomysial antibodies (EMA), and IgA serum were estimated in the patients with peptic ulcers. Celiac disease was diagnosed with serology, endoscopy, and histopathology in 250 (14%) of all cases undergoing endoscopy. Peptic ulcers were diagnosed in 74 patients (4.2%) of all cases undergoing endoscopy. tTGA and EMA (+) levels were determined in 22 (29%) of the 74 patients with peptic ulcers, and then the presence of peptic ulcers was investigated in the upper gastrointestinal system using gastrointestinal endoscopy, followed by histopathological confirmation of celiac disease. HP infection was present in 14 (63%) of the patients with celiac disease and in 23 (44%) of non-celiac peptic ulcers; the difference was not statistically significant (p = 0.12). In the total ulcer group, 10.8% (8/74) of patients with celiac peptic ulcers were negative for HP infection, whereas 21% (8/37) of HP-negative patients with ulcers had celiac disease. There exists a high risk of celiac disease in children with peptic ulcers. We thus recommend celiac disease to be investigated, particularly in HP-negative patients with peptic ulcers but with no history of NSAID use.

Prevalence of celiac disease serological markers in a cohort of Italian rheumatological patients.

To assess the prevalence of celiac disease (CD) serological markers in a cohort of patients referred to an Italian rheumatological outpatient clinic. Current guidelines do not suggest CD screening in patients with rheumatological diseases and these subjects are not considered to be at high risk for CD. A total of 230 sera of rheumatological patients referred to the Division of Internal Medicine at the Department of Medical and Surgical Sciences between January 2005 and December 2013 were screened for CD by testing IgA antitransglutaminase (TTG IgA), IgG deamidated gliadin peptides (DGP IgG) and IgA antiendomysium (EMA) antibodies. Of the 230 patients tested, 67 had a diagnosis of rheumatoid arthritis (RA), 52 Sjögren's syndrome (SjS), 42 systemic sclerosis (SCL), 35 systemic lupus erythematosus (SLE), 15 mixed connective tissue disease, 11 polymyositis and 10 dermatomyositis. TTG IgA antibodies were identified in 7/230 cases (3%), 3 in SjS (3/42 - 5.8%), 2 in SCL (2/42 - 4.8%), 1 in RA (1/67 - 1.5%) and 1 in SLE sera (1/35 - 2.8%). All the seven sera were also positive for DGP IgG and EMA IgA. DGP IgG were the most frequent antibody detected, being found in 16 (7%) sera. This study identified a high prevalence of CD antibodies in adult patients referred to a rheumatology outpatient clinic. These results highlight the importance of CD screening in subjects presenting with rheumatological features.

Weaning and complementary feeding in preterm infants: management, timing and health outcome.

The introduction of solid food is necessary for any infant in order to provide adequate nutrition because when they grow up milk is insufficient for their nutritional needs. Infants born preterm have increased nutritional requirements. The high nutrient demands as well as the organ immaturity of preterm infants combine to render it difficult to achieve dietary intakes that will allow preterm infants to match their in utero growth rates. Current guidelines for the introduction of solid food to term infants cannot be directly translated to preterm infants. For preterm infants such guidelines are lacking. Based on the limited available evidence, it could be concluded that a corrected age of 3 months (13 weeks) may be an appropriate age to start introducing solid food for most preterm infants. About celiac disease (CD), gluten may be introduced into the infant's diet anytime between 4 and 12 completed months of age. In children at high risk for CD, earlier introduction of gluten (4 vs 6 months or 6 vs 12 months) is associated with earlier development of CD autoimmunity (defined as positive serology) and CD, but the cumulative incidence of each in later childhood is similar. Relatively to weaning and allergies, the European Society of Pediatric Allergy and Clinical Immunology and the European Society for Paediatric Gastroenterology Hepatology and Nutrition have produced joint guidelines. They recommend exclusive breastfeeding for 4-6 months or use of hypoallergenic formulas if exclusive breastfeeding is not possible. In addition, The American Academy of Pediatrics recommendations now state that there is no evidence to recommend maternal dietary restrictions during pregnancy or breastfeeding. However, there is no evidence that delaying introduction of solids including allergenic foods after 4-6 months is protective.

Machine Learning in Detection of Undiagnosed Celiac Disease

Machine Learning in Detection of Undiagnosed Celiac Disease

Birth weight, sex, and celiac disease: a nationwide twin study.

ObjectiveEarlier research suggests that birth weight may be associated with celiac disease (CD), but the direction of association has been unclear potentially due to confounding effect from genetic and intrafamilial factors. Through within-twin analyses, we aimed to minimize confounding effects such as twins that share genetic and early environmental exposures.Materials and methodsUsing the Swedish Twin Registry, we examined the birth weight of 146,830 twins according to the CD status. CD was defined as having villous atrophy according to a small intestinal biopsy reports.ResultsThe prevalence of diagnosed CD was 0.5% (n=669), and we included 407 discordant pairs of CD–non-CD twins. Comparing the 669 CD patients with non-CD twins, the association between birth weight and future CD was not statistically significant (odds ratio [OR] per 1000 g increase in birth weight: 1.16; 95% confidence interval [CI]=0.97–1.38). In males, the association was positive and statistically significant (OR=1.50; 95% CI=1.11–2.02). However, the association was not significant in within-pair analyses for both dizygotic and monozygotic twins and for both sexes.ConclusionThis population-based study found that in male twins, higher birth weight was associated with higher risk of CD. However, when comparing discordant twin pairs in within-twin pair analyses, there was no statistically significant association between birth weight, intrauterine growth, and future risk of CD.

Is Blood Transfusion Linked to Celiac Disease? A Nationwide Cohort Study.

The vast majority of patients with celiac disease (CD) have disease-specific antibodies. If such antibodies-or other blood-borne factors that cause CD-are transmissible, it might be reflected by a higher risk of CD in individuals who receive blood from donors with incipient CD. In a retrospective nationwide cohort study of 1,058,289 individuals in Sweden who received a blood transfusion between 1968 and 2012, we examined the risk of transmission of CD (defined as having villous atrophy on small intestinal biopsy) using Cox regression. We also examined whether there were clusters of CD patients who received blood transfusions from the same donor independent of the known donor CD status. Overall, 9,455 patients who had undergone transfusions (0.9%) received a blood transfusion from a donor who had been diagnosed with CD. Of these, 14 developed CD, which corresponds to a hazard ratio of 1.0 (95% confidence interval: 0.9, 1.2) compared with recipients of transfusions from unaffected donors. There were no cases of CD among persons who received plasma or platelet units from donors with CD. We found no evidence of CD clustering among recipients of blood from individual donors (P for trend = 0.28). Our results suggest that CD is not transmitted through blood transfusions.

Similar Responses of Intestinal T Cells From Untreated Children and Adults With Celiac Disease to Deamidated Gluten Epitopes

Celiac disease is a chronic small intestinal inflammatory disorder mediated by an immune response to gluten peptides in genetically susceptible individuals. Celiac disease is often diagnosed in early childhood, but some patients receive a diagnosis late in life. It is uncertain whether pediatric celiac disease is distinct from adult celiac disease. It has been proposed that gluten-reactive T cells in children recognize deamidated and native gluten epitopes, whereas T cells from adults only recognize deamidated gluten peptides. We studied the repertoire of gluten epitopes recognized by T cells from children and adults. We examined T-cell responses against gluten by generating T-cell lines and T-cell clones from intestinal biopsies of adults and children and tested proliferative response to various gluten peptides. We analyzed T cells from 14 children (2-5 years old) at high risk for celiac disease who were followed for celiac disease development. We also analyzed T cells from 6 adults (26-55 years old) with untreated celiac disease. All children and adults were positive for HLA-DQ2.5. Biopsies were incubated with gluten digested with chymotrypsin (modified or unmodified by the enzyme transglutaminase 2) or the peptic-tryptic digest of gliadin (in native and deamidated forms) before T-cell collection. Levels of T-cell responses were higher to deamidated gluten than to native gluten in children and adults. T cells from children and adults each reacted to multiple gluten epitopes. Several T-cell clones were cross-reactive, especially clones that recognized epitopes from γ-and ω-gliadin. About half of the generated T-cell clones from children and adults reacted to unknown epitopes. T-cell responses to different gluten peptides appear to be similar between adults and children at the time of diagnosis of celiac disease.