• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.22 no.4
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• pp.350-357
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• 2019

Purpose: This study aimed to evaluate a possible association between the anti-tissue transglutaminase antibody (anti-tTG) titer and stage of duodenal mucosal damage and assess a possible cut-off value of anti-tTG at which celiac disease (CD) may be diagnosed in children in conjunction with clinical judgment. Methods: This observational study was conducted at a gastroenterology clinic in a tertiary hospital from April 2012 to May 2013. Seventy children between 6-months and 18-years-old with suspected CD underwent celiac serology and duodenal biopsy. Statistical analyses were done using SPSS 16. Diagnostic test values were determined for comparing the anti-tTG titer with duodenal biopsy. An analysis of variance and Tukey-Kramer tests were performed for comparing the means between groups. A receiver operating characteristics curve was plotted to determine various cut-off values of anti-tTG. Results: The mean antibody titer increased with severity of Marsh staging (p<0.001). An immunoglobulin (Ig) A-tTG value at 115 AU/mL had 76% sensitivity and 100% specificity with a 100% positive predictive value (PPV) and 17% negative predictive value (NPV) for diagnosis of CD (p<0.001, 95% confidence interval [CI], 0.75-1). Conclusion: There is an association between the anti-tTG titer and stage of duodenal mucosal injury in children with CD. An anti-tTG value of 115 AU/mL (6.4 times the upper normal limit) had 76% sensitivity, 100% specificity, with a 100% PPV, and 17% NPV for diagnosing CD (95% CI, 0.75-1). This cut-off may be used in combination with clinical judgment to diagnose CD.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.19 no.4
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• pp.229-235
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• 2016

Purpose: To study whether breastfeeding and breastfeeding status during gluten introduction influences the age at diagnosis of celiac disease (CD). In addition to study, whether the timing of gluten introduction influences the age at diagnosis of CD. Methods: It was a hospital based observational study. Total 198 patients diagnosed with CD as per modified European Society of Pediatric Gastroenterology, Hepatology and Nutrition (2012) criteria, aged between 6 months to 6 years were included. Detail history taken with special emphasis on breastfeeding and age of gluten introduction. Standard statistical methods used to analyze the data. Results: $Mean{\pm}standard$ deviation age of onset and diagnosis of CD in breastfed cases was $2.81{\pm}1.42$ years and $3.68{\pm}1.55$ years respectively as compared to $1.84{\pm}1.36$ years and $2.70{\pm}1.65$ years respectively in not breastfed cases (p<0.05). Those who had continued breastfeeding during gluten introduction and of longer duration had significantly delayed onset of disease. The age at onset of CD was under one year in 40.42% of the cases, who had started gluten before 6 months of age compared to only 12.58% of those who had started gluten later (p<0.001). The proposed statistical model showed that two variables, i.e., breast feeding status during gluten introduction and age at gluten introduction positively influencing the age at diagnosis of CD. Conclusion: Delayed gluten introduction to infant's diet along with continuing breastfeeding, delays symptomatic CD. However, it is not clear from our study that these infant feeding practices provide permanent protection against the disease or merely delays the symptoms.

• Clinical and Experimental Pediatrics
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• v.64 no.6
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• pp.301-309
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• 2021

Background: Celiac disease (CD) is a chronic autoimmune enteropathy. It results from genetic predisposition and exposure to gluten-containing food. The prevalence and presentation of CD vary among populations. Purpose: This study aimed to describe the prevalence and clinical characteristics of CD in children in Bahrain. Methods: We retrospectively reviewed the medical records of children diagnosed with CD in the pediatric department, Salmaniya Medical Complex, Bahrain, in 1988-2018. Their clinical, biochemical, serological, and histopathological findings were documented. Adherence to the recommended gluten-free diet (GFD) was assessed. Results: Of 86 patients with CD, 67 were included. The CD prevalence was 0.02%. A significant increase in prevalence in the last decade was observed (P<0.0001). Thirty-eight patients (56.7%) were males. The median (interquartile range) age at presentation was 4.45 (1.5-7.3) years. A family history of CD was positive in 13 out of 43 patients (30.2%). Pallor and failure to thrive were the most common presentations. The most frequent associated disease was iron-deficiency anemia in 23 patients (69.7%). Positive serology was found in 32 of 45 patients (71.1%). Marsh-Oberhuber type III was found in 16 of 35 patients (45.7%). Seropositive patients were significantly older (P=0.025) and had more severe duodenal histology (P=0.002). Adherence to GFD was poor in 27 patients (64.3%). Conclusion: This study revealed a significant increase in CD prevalence over the last decade. Atypical presentations were frequent. Most patients had poor adherence to GFD.

• International journal of advanced smart convergence
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• v.7 no.2
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• pp.101-111
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• 2018

Celiac disease (CD) is an immune-mediated enteropathy of small intestine diagnosed in both childhood and adulthood. CD is caused by gluten, which produces gliadorphin during its digestion. The enzyme dipeptidyl peptidase-4 (DPP4) breaks gliadorphin down nevertheless the last tripeptide remains and eventually inhibits DPP4, thus slowing down its process. Therefore, the idea is to produce an additional DPP4 enzyme which is crucial. Consequently, the functional DPP4 gene was cloned into pCDNA3 intermediate (FLAG+DPP4) vector and finally a recombinant plasmid pSB1C3 (Andersons promoters+FLAG+DPP4) was constructed using synthetic biology. Normally, a DPP4 inhibitor is used as a cure for diabetes. Another important concern was overexpression of DPP4, which might lead to diabetes, accordingly the work was also performed for the regulation of the DPP4 gene expression. In this regard, three types of Anderson promoters (strong, moderate and weak) were utilized to study the control overexpression. This is the first report of idealistic trial for control the exogenous DPP4 gene-expression by molecular biologic tools.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.23 no.4
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• pp.397-404
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• 2020

Purpose: Synbiotics can alleviate some intestinal pathologies or prevent trigger mechanisms for some diseases such as celiac disease (CD). If patients with high levels of anti-tissue transglutaminase (anti-tTG) immunoglobulin A (IgA) antibodies have normal duodenal histology, they are followed as potential CD patients. The aim of this study was to investigate the effect of synbiotic use on the blood levels of anti-tTG antibodies in children. Methods: Eighty-two patients with high anti-tTG levels were included in this study. Patients were randomly divided into two groups. The synbiotic group was treated with a daily dose of a synbiotic including multi-strain probiotics for 20 days. The control group was not administered any medication. Anti-tTG values at baseline and repeat measurements and the percentage change in anti-tTG levels between groups were compared. Results: The anti-tTG level at baseline was 36 U/mL (interquartile range [IQR], 26.4-68 U/mL) in the synbiotic group, and it decreased significantly to 13 U/mL (IQR, 6.5-27.5 U/mL) after 20 days (p<0.05). The anti-tTG level at baseline was 46 U/mL (IQR, 31-89 U/mL) in the control group, which also decreased significantly to 23 U/mL (IQR, 7-41 U/mL) after 20 days (p<0.05). Anti-tTG levels exhibited 73% and 56% decreases in the synbiotic and control groups, respectively (p<0.05). Conclusion: It may be speculated that a synbiotic supplementation can contribute to decreasing anti-tTG levels in children with potential CD.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.24 no.5
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• pp.492-499
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• 2021

Purpose: Celiac disease (CD) is an autoimmune disorder of the small intestine caused by an abnormal immune response to gluten proteins and is often characterized by gastrointestinal symptoms. Food allergy (FA) is an adverse immune sensitivity to ingested food proteins leading to inflammation in various organs including the gastrointestinal tract. The relationship between CD and FA remains unclear. This study aimed to assess the prevalence and clinical relevance of immunoglobulin E (IgE)-mediated food sensitization in children with CD. Methods: Fifty-nine children diagnosed with CD were reviewed for clinical symptoms and evidence of IgE-sensitization to food and airborne allergens using the PolyCheck method. Results: IgE-mediated sensitization has been diagnosed in 20.3% of children with CD (CD/A). In the CD/A group, 58.3% of children were sensitized to food and 66.7% to airborne allergens. Further, 41.7% of patients with CD and allergy reported gastrointestinal tract symptoms associated with the ingestion of sensitizing foods. Analysis of the clinical status revealed that the incidence of other allergic disorders in the CD/A group was as follows: atopic dermatitis (33.3%), asthma (25.0%), and allergic rhinitis (16.7%). The percentage of eosinophils was significantly higher in the CD/A group than in the CD group (0.33±0.25 vs. 0.11±0.09; p=0.006). Conclusion: The diagnosis of CD does not exclude FA. The gastrointestinal symptoms in children with CD may be the result of both CD and FA; therefore, children with CD should be evaluated for the presence of FA regardless of age.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.25 no.2
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• pp.138-146
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• 2022

Purpose: Children with celiac disease (CD) are at an increased risk of low bone mineral density (BMD) owing to malabsorption of fat-soluble vitamins, inflammation, and malnutrition. This study aimed to determine the prevalence and risk factors for low BMD in Iranian children with CD. Methods: This prospective cohort study examined 149 Iranian children with CD between 2011 and 2018 at Zabol University of Medical Sciences. BMD was measured using dual-energy X-ray absorptiometry. Demographic, clinical, and laboratory data were collected from patients' medical records. Logistic regression analysis was performed to identify the factors associated with low areal BMD (BMD-Z <-2) in the lumbar spine and femoral neck. Descriptive data were analyzed using the mean, standard deviation, and relative frequency. Data were analyzed using the chi-square test, t-test, and analysis of variance. Results: Of the 149 children with CD, 27.5% had osteoporosis. The mean body mass index (BMI) Z score was -1.28±1.2. Lower BMI was associated with a higher likelihood of BMD-Z (odds ratio 2.17; p≤0.05). Conclusion: Overall, the findings of this study showed that there was no correlation among Marsh classification, presence of specific human leukocyte antigens, and low BMD in Iranian children with CD. BMI can be a predictor of bone density in children with CD and may be applied clinically in early screenings to evaluate the bone health status in these children.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.25 no.4
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• pp.312-320
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• 2022

Purpose: Screening serologic tests are important tools for the diagnosis of celiac disease (CD). Immunoglobulin (Ig)G anti-deamidated gliadin peptide (anti-DGP) is a relatively new autoantibody thought to have good diagnostic accuracy, comparable to that of anti-tissue transglutaminase (anti-tTG) antibody. Methods: Pediatric patients (n=86) with a clinical suspicion of CD were included. Duodenal biopsy, anti-tTG, and IgG anti-DGP antibody tests were performed. The patients were divided into CD and control groups based on the pathological evaluation of duodenal biopsies. The diagnostic accuracy of serological tests was determined. Results: IgA anti-tTG and IgG anti-DGP antibodies were positive in 86.3% and 95.4% of patients, respectively. The sensitivity, specificity, and diagnostic accuracy of the IgA anti-tTG test were 86.3%, 50.0%, and 68.6%, respectively, and those of the IgG anti-DGP test were 95.4%, 85.7%, and 90.7%, respectively. The area under the receiver operating characteristic (ROC) curve was 0.84 (95% confidence interval [CI], 0.74-0.91) for IgA anti-tTG test and 0.93 (95% CI, 0.86-0.97) for IgG anti-DGP test. The comparison of IgA anti-tTG and IgG anti-DGP ROC curves showed a higher sensitivity and specificity of the IgG anti-DGP test. Conclusion: IgG anti-DGP is a reliable serological test for CD diagnosis in children. High tTG and DGP titers in the serum are suggestive of severe duodenal atrophy. The combined use of IgA anti-tTG and IgG anti-DGP tests for the initial screening of CD can improve diagnostic sensitivity.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.26 no.1
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• pp.50-57
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• 2023

Purpose: The purpose of this study was to determine the pattern of human leukocyte antigen (HLA)-DQ genotype in children diagnosed with celiac disease (CD) (biopsy proven), and to compare this with a control group; and secondarily, to correlate HLA genotypes with clinical profiles of CD. Methods: This cross-sectional comparative observational study included 26 controls and 52 patients diagnosed with CD who presented at Sir Padampat Mother and Child Health Institute, Jaipur, from May, 2017 to October, 2018. HLA DQ genotype was assessed for each patients and correlated with clinical profiles. Results: HLA DQ2/DQ8 genotypes were significantly more common in CD (present in 100.0% cases) than in controls (23.1%) in Northern India (Rajasthan). When HLA DQ2.5 and DQ8 were present together, individuals had significantly more atypical presentations and severe findings on duodenal biopsy. Similarly, patients with the HLA DQ 2.5 genotype were also predisposed to more severe endoscopic findings, while HLA DQ2.2 predisposed them to less severe biopsy findings. HLA DQ8 was significantly associated with later age at diagnosis (>5 years) and shorter stature. The highest HLA DQ relative risk (RR) for CD development was associated with HLA DQ2.5 and DQ2.2 in combination, followed by HLA DQ2.5 and DQ8 in combination, while HLA DQx.5 and HLA DQ2.2 together had the lowest risk. Conclusion: HLA DQ2/DQ8 genotypes are strongly associated with pediatric CD patients in northern India. These genotypes and their combinations may be associated with different clinical presentations of CD, and may help predict severity of CD.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.24 no.2
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• pp.218-229
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• 2021

Purpose: Serological tests of tissue transglutaminase (TTG) and deamidated gliadin (DGP) antibodies for celiac disease diagnosis show conflicting correlation with histology in young children and in type 1 diabetes mellitus (T1DM). Tests' ability to predict histology and cutoff values based on age and T1DM was evaluated. Methods: A retrospective study of children who had celiac serological tests between 6/1/2002 and 12/31/2014 at a pediatric hospital. Results: TTG IgA displayed similar results in predicting histology between <4.0 and ≥4.0 years age groups with sensitivity 98% and 93%, and specificity 88% and 86%, respectively. In children <4.0 years old, sensitivity for DGP antibodies was 100% and specificity 94%; in ≥4.0 years age groups, sensitivity was 60%, 88% for DGP IgA and IgG and specificity 95%, 96%, respectively. TTG IgA had low specificity in patients with T1DM compared with non-T1DM, 42% vs. 91%. Positive TTG IgA with normal histology was associated with higher T1DM prevalence at 36% compared with negative tests at 4%. Finally, the TTG IgA cutoff value was higher in T1DM at 36 vs. 16.3 units in non-T1DM. DGP IgG cutoff showed similar values between age groups; TTG IgA and DGP IgA cutoffs were lower in <4.0 years at 8.3 and 11.9 units than ≥4.0 years at 23.4 and 19.9, respectively. Conclusion: TTG IgA is sufficient for the <4.0 years age group and DGP antibodies had no advantage over TTG IgA in older children. The cutoff value to determine a positive TTG IgA should be higher for children with T1DM.