IgA-tTG Levels Research Articles

The overlap between type 1 diabetes and celiac disease in children and the role of tTG-IgA positivity in endoscopy decision.

Celiac Disease (CD)-related antibody positivity in children with Type 1 Diabetes (T1D) may fluctuate and become negative spontaneously. There are uncertainties about the optimal tTG-IgA titre and timing of endoscopy in the diagnosis of CD, and this study aimed to contribute to the debate on the tTGA-IgA threshold titre for endoscopy decisions in children with T1D. The data of 991 children with T1D who had undergone serologic evaluation for CD were analysed retrospectively. The tTG-IgA positivity rate and the upper limit of normal (ULN) tTG-IgA positivity were assessed. Participants were grouped according to the frequency, course and test results of tTG-IgA tests. Those with and without histopathologic diagnosis of CD by endoscopic biopsy were compared in terms of tTG-IgA screening time and tTG-IgA predictive values. In 10.2% (n:101) of all cases, tTG-IgA antibody was positive and endoscopic biopsy was performed in 68.3% (n:69) of these cases. Of all cases, 4.3% (n:43) were diagnosed with CD by endoscopic biopsy. A tTG-IgA titre of 7xULN and above was found to be the best predictive value for the diagnosis of CD with 79.1% sensitivity, 80.8% specificity 87.2% positive predictive value and 70% negative predictive value. Approximately 10% of antibody positive cases showed fluctuating and low titre positivity, and no CD was detected by endoscopic biopsy in the group with fluctuating antibody course. The results of our study suggest that endoscopy in children with tTG-IgA levels 7xULN or above may prevent both false positive results and missed cases.

Association of Celiac Disease and H. pylori Infection with ATG5 Polymorphism and Interleukin-33

Background: Celiac disease (CD) is an inflammatory small intestine autoimmune disease. The study aims to investigate the association and the detection of ATG5 polymorphism between celiac disease (CD) and H. pylori infection, and the association with Interleukin-33 (IL-33).Methods: The study groups included patients from Iraq, ages 4 to 35. Two primary patient groups were created: sixteen had positive H. pylori and celiac disease, and thirty had positive CD and negative H. pylori disease. The levels of tissue transglutaminase IgA (TTG IgA), H. pylori IgG, and IL-33 were measured using the ELISA method. The primers were amplified using PCR.Results: With celiac disease, the patient group's TTG IgA levels increased dramatically. The test also showed significant variations (P=0.054) in the H. pylori IgG levels between the patient and control groups. The H. pylori seropositivity test showed a statistically significant difference (p ≤0.033) between seropositive and seronegative individuals, while the patient group's IL-33 levels did not significantly differ (P ≤0.299) from the control group.Conclusions: Our results showed that CD is more common in women and occurs in the age range of 24-35 years. It also showed that the mutant variant of ATG5 is associated with CD, and the significance of H. pylori IgG serum levels in the patient group may indicate that the bacteria involved in CD. Furthermore, H. pylori infection is more strongly linked to serum IL-33 levels than CD.Keywords: Celiac disease; H. pylori; PCR; IL-33; ATG5 polymorphism

WHICH IS IMPORTANT? GLUTEN FREE DIET OR INFLAMMATORY BOWEL DISEASE MEDICATIONS IN SUBJECTS WITH AN OVERLAP WITH CELIAC DISEASE AND INFLAMMATORY BOWEL DISEASE: OBSERVATIONS FROM A CASE SERIES AT A LARGE ACADEMIC CENTER

Abstract INTRODUCTION Celiac disease (CeD) and inflammatory bowel disease (IBD) are autoimmune diseases of the bowel with similar clinical symptoms. This study aims to characterize the clinical course of both diseases in subjects with overlap of CeD and IBD (CeD+IBD) on a gluten free diet (GFD) and IBD medications. METHODS We conducted a retrospective study of demographic and serological characteristics in subjects with CeD+ IBD at a large academic center using appropriate International Classification of Disease (ICD)-10 codes from 2017 to June 2022. RESULTS 36 subjects had IBD +CeD. 96% of subjects were Caucasian and 67% were female. The diagnosis of CeD post-dated the diagnosis of IBD by 3.6 years. Ulcerative colitis (UC) and Crohn’s disease (CD) occurred equally in IBD +CeD. About 75% of subjects had L2+L3, B1 phenotype per Montreal classification. 44% of UC +CeD subjects had pancolitis with 72% of them being classified as S0 (never severe) per Paris classification. 83% of subjects initiated a self-taught GFD. Only 17% of subjects sough advice from a celiac dietician. Mean duration at which GFD was initiated was 0.7 yrs from the initial diagnosis of CeD. Only 1/36 subjects followed a strict GFD during 6.5 years of follow up. The second and third assessment of GFD happened after a mean of 3.7 yrs and 5.2 yrs from the time of initiation of a GFD with only 1/36 subjects adhering to a strict GFD at these time points. Serum tTG IgA levels were tested on average at 4, 91, 154, 186 and 192 weeks from the diagnosis of CeD, with a consistent drop in mean tTG IgA titers to 45, 33, 19, 25 and 4 respectively. Only 1 subject got tTG IgA measurements over the next 250 weeks of follow up. Over a 10.1 year follow up since the diagnosis of IBD, descending proportions of subjects needing IBD medications were as follows: topical 5-ASA (aminosalicyates) (19/36)>oral steroids (18/36)> anti-TNF (tumor necrosis factor) (18/36)> anti-integrins (12/36)> azathioprine (10/36)> anti-IL12/23 (8/36)> topical 5-ASA (4/36)> MTX (methotrexate) (5/36)> topical steroids at 2/36. Mean time to initiation of IBD medications (in weeks) after GFD initiation as a reference point were in an order of oral 5-ASA (-67) < anti-TNF (-39) < AZA (-14) <MTX (-6) < topical 5-ASA (-2) <oral steroids (82) <anti-integrins (124) <anti-IL 12/23 (137) CONCLUSIONS Majority of subjects depended on a self-educated GFD. A small proportion of CeD +IBD subjects were assessed per clinical guidelines with respect to adherence to a GFD, serology. At least 50% of subjects with CeD+IBD needed escalation of IBD treatment to biologics and/or steroid rescue over 10 years despite initiation of GFD (albeit suboptimal). We need to further substantiate these findings with exclusive IBD and celiac control groups. We suggest establishing CeD centers at tertiary hospitals for adequate clinical guideline adherence.

Serum positivity of serum anti-tissue transglutaminase immunoglobulin A antibodies in Japanese children with inflammatory bowel disease.

Serum anti-tissue transglutaminase immunoglobulin A antibody (tTG-IgA) is a screening test for celiac disease (CeD). In recent years, there have several reports of combined inflammatory bowel disease (IBD) and CeD in children. The purposes of this study are to research the positivity of the tTG-IgA antibody in Japanese children, and whether IBD and CeD co-occur. We examined tTG-IgA as a screening test for CeD in symptomatic pediatric patients with IBD (cases) and those without IBD (controls, non-IBD). Those with tTG-IgA levels of 10U/mL or higher were considered positive. All patients had routine biopsy specimens taken from the second part and bulbus of the duodenum, and were evaluated histologically based on the Marsh classification. Thirty-one patients in the IBD group and 53 patients in the non-IBD group were included. The tTG-IgA was positive in five cases (5.9%) and median titer of positive cases was 12.3U/mL (10.2-41.7). One patient in the IBD group (3.2%) and four patients in the non-IBD group (7.8%) were positive for tTG-IgA. No cases showed histological features of CeD. There were no statistically significant differences in age, sex, symptoms and laboratory tests between the tTG-IgA positive and negative groups. Patients among the IBD and the non-IBD groups that were tTG-IgA positive demonstrated symptoms after wheat consumption. We identified a patient who was positive for tTG-IgA antibodies who experienced abdominal symptoms due to wheat ingestion, indicative of subclinical CeD. Further investigation is needed to clarify the co-occurrence of IBD and CeD among Japanese children.

Frequency of Celiac Disease in Microcytic Anemia Patients of Nowshera

Background: Celiac disease a chronic gastrointestinal disorder is caused by an immune response to the gluten. Numerous studies have been conducted worldwide on the relationship between anemia and celiac disease. Objective: To find out the frequency of celiac disease in microcytic anemia patients of Nowshera Methodology: The current study was cross sectional carried out at the Gastroenterology department, Qazi Hussain Ahmad Medical Complex, Nowshera from October 2021 to October 2022. For serological diagnosis of the celiac disease, all the patients were tested for IgA and IgG tTG (anti-tissue transglutaminase). OesophagoGastroDuodenoscopy (OGD) was done for all the patients with raised level of IgA and IgG tTG (anti-tissue transglutaminase). All the analysis of collected data was done by employing IBM SPSS version 24. Results: In this study a total of 300 patients with microcytic anemia were enrolled. There were 165 (55%) female participants while 135 (45%) patients were male. IgA and IgG tTG (anti-tissue transglutaminase) levels were raised in 15 (5%) patients amongst 300 patients with microcytic anemia. In duodenal biopsy of 15 patients with celiac disease, Marsh I was observed in 4 (33.33%) patients, Marsh II in 5 (41.67%) patients, Marsh III in 3 (25%) patients, while 3 (20%) cases showed normal histo-pathological findings. Thus the overall frequency of celiac disease amongst microcytic anemia patients was 15 (5%). Conclusion: Our study concludes that celiac disease is more prevalent amongst the patients with microcytic anemia. The microcytic anemia can be considered as additional gastrointestinal manifestation of the celiac disease. Keywords: Frequency; Celiac disease; Microcytic anemia

A191 PERSISTENT BENEFIT OF DIETITIAN-LED GLUTEN-FREE DIET EDUCATION AT CD DIAGNOSIS ON DIETARY ADHERENCE IN CHILDREN AND ADULTS WITH TYPE 1 DIABETES AND CELIAC DISEASE

BackgroundCeliac disease (CD) is a common autoimmune comorbidity of type 1 diabetes (T1D) with a gluten-free diet (GFD) being the current gold standard treatment for this condition. Adherence to a GFD can be impacted by several factors including dietetic counselling, yet little is known about the impact of clinic-based interventions on long-term GFD adherence in this population.AimsTo prospectively evaluate the impact of a dietitian-led GFD education intervention on adherence to a GFD in children and adults with T1D and CD over a 3-year period.MethodsA cohort of N=62 pediatric and adult subjects who screened seropositive for CD as part of the CD-DIET clinical trial were followed over a 3-year period post-CD diagnosis and assessed on the basis of the GFD education regimen they received at initial CD diagnosis. This included 3 groups: 1) intensive dietitian training (IDT = 5 dietitian visits over 1 year while following GFD), 2) single dietitian training (SDT = 1 GFD training session after 1 year of following GCD) and 3) no dietitian training (NDT) at CD diagnosis. Annual visits included serologic testing of TTG-IgA titres, anthropometric assessments and the completion of questionnaires evaluating diet and adherence to a GFD. Data was analysed longitudinally using linear mixed effects and generalized estimating equations (GEE) regression modeling adjusting for the fixed effects of age, sex, duration of diabetes and time.ResultsAt baseline, participants who received IDT (n=15), SDT (n=16) and NDT (n=31) represented 24.2%, 25.8%, and 50.0% of the cohort, respectively. Over the 3-year study period, participants in the IDT group had the greatest odds of self-reporting being a GFD, with odds 4.3 (95%CI: 1.1 to 16.4; P=0.033) and 9.5 (95%CI: 2.7 to 33.7; P<0.001) greater than the SDT and NDT groups, respectively. The assessment of daily gluten intakes less than 10mg, as recommended for a GFD, revealed a lack of differences between the IDT and SDT groups. In contrast, the NDT group had significantly lower odds of meeting this threshold relative to those who received IDT (OR=0.2; 95%CI: 0.04 to 0.56; P=0.004). No longitudinal differences in TTG-IgA levels were seen between groups over the 3-year period.ConclusionsIn diabetes patients greater contact with a dietitian at CD diagnosis was associated with higher levels of GFD adherence over time, which was not reflected in follow-up Serologic evaluation. These findings highlight the importance of nutritional support in patients with both diabetes and celiac disease at the time of CD diagnosis. In addition, following TTG-IgA alone does not fully inform dietary compliance to a GFD.Diet teaching stratification Diet assignmentFunding AgenciesJuvenile Diabetes Research Foundation / PSI

Recommendations for Clinical Decision-making in Children with Type 1 Diabetes and Celiac Disease: Type 1 Diabetes and Celiac Disease Joint Working Group Report

It is well-known that in children with type 1 diabetes (T1D), the frequency of Celiac disease (CD) is increased due to mechanisms which are not fully elucidated but include autoimmune injury as well as shared genetic predisposition. Although histopathologic examination is the gold standard for diagnosis, avoiding unnecessary endoscopy is crucial. Therefore, for both clinicians and patients’ families, the diagnosis of CD remains challenging. In light of this, a joint working group, the Type 1 Diabetes and Celiac Disease Joint Working Group, was convened, with the aim of reporting institutional data and reviewing current international guidelines, in order to provide a framework for clinicians. Several controversial issues were discussed: For CD screening in children with T1D, regardless of age, it is recommended to measure tissue transglutaminase-immunoglobulin A (tTG-IgA) and/or endomysial-IgA antibody due to their high sensitivity and specificity. However, the decision-making process based on tTG-IgA titer in children with T1D is still debated, since tTG-IgA titers may fluctuate in children with T1D. Moreover, seronegativity may occur spontaneously. The authors’ own data showed that most of the cases who have biopsy-proven CD had tTG-IgA levels 7-10 times above the upper limit. The decision for endoscopy based solely on tTG-IgA levels should be avoided, except in cases where tTG-IgA levels are seven times and above the upper limit. A closer collaboration should be built between divisions of pediatric endocrinology and gastroenterology in terms of screening, diagnosis and follow-up of children with T1D and suspicious CD.

Repeat Biopsy to Assess Duodenal Healing in Children With Celiac Disease and Eosinophilic Gastrointestinal Disorders.

A retrospective chart review was performed of children with CD and EGID seen at the Children's Hospital of Philadelphia between 2003 and 2018. Data collected included duodenal biopsy pathology, celiac serology including tTG-IgA, and symptom reports. Duodenal healing was defined as normal villous architecture and no intraepithelial lymphocytes. These data were compared with tTG-IgA level. Data were analyzed with Fisher exact test and t test methods. Thirty-nine patients had normal IgA and diagnoses of both CD and EGID. At second biopsy, 44% (17/39) of patients showed no histologic evidence of active CD and 36% (14/39) of patients had negative tTG-IgA values. Sixty percent (9/15) of patients with no evidence of CD on biopsy had abnormal tTG-IgA levels, and 57% (8/14) of patients with normal tTG-IgA levels had evidence of active disease on biopsy. The data show that an abnormal tTG-IgA drawn after initiation of a gluten-free diet is not correlated with duodenal mucosal injury in pediatric patients with CD and EGID. This suggests that serologic surveillance with tTG-IgA is not sufficient to monitor CD intestinal healing in this patient cohort. Persistent elevations of tTG-IgA in CD patients with normal duodenal biopsies should prompt investigation into other potential causes.

Response of Hepatitis B Vaccine in Children with Celiac Disease – An Experience at Ayub Teaching Hospital, Abbottabad Pakistan

Background: Celiac Disease (CD), characterized by chronic small intestinal inflammation, is an immune-mediated disorder, with a strong family history and association with DQ2 HLA haplotype. It has been postulated that children with CD show less response to hepatitis B vaccine due to overexpression of HLA-DQ2 haplotype. This study was done to determine the response of hepatitis B vaccine in children with CD in our tertiary care setting in the Hazara region of eastern Khyber Pakhtunkhwa, Pakistan.Material and Methods: This cross-sectional study was conducted in the Pediatrics outpatient department (OPD) of Ayub Teaching Hospital, Abbottabad Pakistan from April 2018 till March 2020. Children with CD (n=38) aged 1-14 years with completed HBV vaccination, anti-tissue transglutaminase IgA antibody (tTG-IgA) &gt;150 IU/ml and/or typical histological findings of CD on small-bowel biopsy, were included in the study. Hepatitis B surface antibody (HbsAb) titer of ≥10 mIU/ml was taken as antibody positive, while HbsAb levels &lt; 10 mIU/ml were considered as vaccine non-responsive. Data was analyzed using SPSS version 20.0. Chi square test was applied for comparison with P-value &lt; .05 taken as significant.Results: Out of 38 diagnosed cases of CD, 15 (39.5%) were males and 23 (60.5%) were females. Mean age of children was 8.32±3.26 years with an age range of 3-14 years. HbsAb levels ranged from 0.10 to 62.7 mIU/ml with a mean of 11.2+17.42 mIU/ml. HbsAb levels were less than 10.0 IU/ml in 73.7% of children with CD. Small intestinal biopsy was performed in 11 (28.9%) patients. There was a significant relationship between anti tTG-IgA levels and histopathology findings with P-value of .001.Conclusions: In children having celiac disease, there was low rate of protective antibody response to hepatitis B vaccine.

Accuracy of a no-biopsy approach for the diagnosis of coeliac disease across different adult cohorts

ObjectiveWe aimed to determine the predictive capacity and diagnostic yield of a 10-fold increase in serum IgA antitissue transglutaminase (tTG) antibody levels for detecting small intestinal injury diagnostic of coeliac...

Evaluation of the Utility of Amino Acid Citrulline as a Surrogate Metabolomic Biomarker for the Diagnosis of Celiac Disease.

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

Automated Analyzers Are Suited for Diagnosing Celiac Disease Without a Biopsy.

The European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) 2012 guidelines, enabled for the first time, a nonbiopsy approach in the diagnosis of celiac disease (CD). We aimed to prospectively assess 4 tissue-transglutaminase (tTg) IgA assays of 4 random-access analyzers and examine their accuracy in diagnosing CD without a biopsy. We enrolled 186 consecutive children referred to upper endoscopy and intestinal biopsy. One group included 109 patients with positive tTg that was referred for suspected CD. Another group included 77 patients with negative tTg referred because of other indications. All participants had a blood sample taken at the time of endoscopy. Samples were tested with 4 tTg IgA assays on automated analyzers and 1 Elisa kit. All intestinal biopsies were evaluated by a local pathologist, a central pathologist, and a CD expert blinded to each other. CD was diagnosed when full agreement was reached. Analytical performance of the assays included precision with controls and samples, lot to lot variation, and carryover. In our cohort, all tested tTg IgA-automated assays showed sensitivities above 98% and specificities above 99%. ROC analysis demonstrated AUC (area under the curve) >0.99 for all 4 analyzers. The positive-predictive values (PPV) were all >0.99 and negative-predictive values (NPV) were >0.97. The Elisa kit had sensitivity of 95%, specificity of 96%, AUC of 0.96, PPV of 0.98 and NPV of 0.93. CD can be accurately diagnosed without biopsy based on tTg IgA levels at least 10 times the ULN using the 4 high-volume random-access analyzers used in our study.

Optimization of serologic diagnosis of celiac disease in the pediatric setting.

The clinical presentation of celiac disease (CD) varies between children. The objective of this study was to document the pre-test probability for CD based on symptoms and routine laboratory test and to evaluate the performance of two IgA anti-tissue transglutaminase (tTG) assays. We critically reviewed the concept of using multiples of the manufacturer's upper limit of normal (ULN), as proposed in the ESPGHAN guidelines (if IgA tTG is >10 times ULN, no biopsy is needed). The retrospective study included 91 children with newly diagnosed CD and 605 controls (<16 years). All underwent upper endoscopy with small bowel biopsies. Four laboratory parameters and 16 symptoms were registered. All patients were tested for IgA anti-tTG antibodies with assays from Inova Diagnostics and Thermo Fisher Scientific. Some combinations of clinical symptoms and laboratory parameters had a high pre-test probability for CD, such as (combinations of) anorexia, failure to thrive, low ferritin level and elevated AST. The diagnostic performance of both IgA anti-tTG assays was excellent and comparable (no difference in ROC curve area under the curve). At a threshold that corresponds to a specificity of 100% (5 times ULN for Inova Diagnostics and 2 times ULN for Thermo Fisher), the sensitivity was 82% for both assays. At the 10 times ULN threshold, the sensitivity differed between the assays (77% vs. 57%), indicating that such threshold does not completely align interpretation across companies. Our study showed that some combinations of symptoms and aberrant laboratory parameters had a high pre-test probability. The use of the ESPGHAN non-biopsy approach could reduce small bowel biopsies, but thresholds for IgA-tTG levels are not aligned across assays and should be based on predefined likelihood ratios or specificity.

A23 NUTRITIONAL DEFICIENCIES ARE FREQUENT IN CELIAC PATIENTS ON A GLUTEN-FREE DIET, REGARDLESS OF THE DURATION AND COMPLIANCE OF THE DIET

Abstract Background The only available treatment for celiac disease (CD) is adherence to a strict gluten-free diet (GFD). CD is associated with several nutritional deficiencies, which could be explained by malabsorption when the disease is active. However, the magnitude of nutritional deficiencies in treated CD and how this is influenced by the duration and compliance of GFD is less clear. Aims We aim to evaluate the presence of nutritional deficiencies in celiac patients on short term (≤2yrs) vs long-term (&amp;gt;2yrs) GFD, and in those with persistent symptoms or asymptomatic in the follow up. Methods We included consecutive biopsy-proven CD patients attending the McMaster Adult Celiac Clinic. GFD adherence was assessed by validated Celiac Dietary Adherence Test (CDAT) and by anti-tissue transglutaminase antibody IgA(tTG IgA) levels. Serology, vitamins and minerals were measured in blood samples collected at enrolment. Continuous data was expressed as Median (IQR) and categorical data as proportion%. Mann-U-Whitney and Chi2 were used to compare difference between groups. Results We enrolled 171 CD patients (80% female; Median age 43 years). 76/171 (44%) of CD patients were following a GFD for over 2 years. Eighty-two percent of the patients (141/171) had persistent symptoms in the follow up and 80.7% had normal tTG IgA levels. The most common nutritional abnormalities were deficiencies in zinc (56%), iron (23%), copper (20%). Chromium was increased in 74% of patients. There were no differences in nutritional deficiencies between group of patients with short and long-term duration of GFD, nor between those strictly compliant with GFD compared to those fairly compliant (p&amp;gt;0.05). Conclusions Nutritional deficiencies are frequent in celiac patients on a GFD regardless of the presence of symptoms, dietary compliance or duration. The previous suggest that nutrients deficiencies may be more related to GFD nutritional inadequacy rather than malabsorption. Funding Agencies None

Can individuals with celiac disease identify gluten-free foods correctly?

Patients with celiac disease (CD) often report inadvertent gluten exposures and challenges reading labels. The most common cause of non-responsive CD is gluten exposure. We aimed to assess whether recently diagnosed CD patients can determine whether a food is gluten-free based on labeling, and to assess skills over time. A secondary aim was to identify factors associated with label reading proficiency. Inception cohort with follow-up at 6, 12, and 24 months after diagnosis. Participants were asked to determine whether 25 food items were gluten-free based on labeling information. Diet adherence was assessed using the Celiac Diet Assessment Tool (CDAT) and the Gluten-Free Eating Assessment Tool (GF-EAT). 144 adults with newly diagnosed celiac disease were enrolled. The initial quiz at 6 months was completed by 83%. Quizzes were completed by 72% at 12 months and 70% at 24 months. Median overall accuracy scores were: 23/25, 24/25 and 21/25at 6, 12 and 24 months respectively. Gluten-free products with explicit "gluten-free" claims had the fewest errors. Quiz scores were not correlated with tTG IgA levels, or CDAT or GF-EAT scores. Diet adherence was generally good (>85% with CDAT <13 suggesting adequate GFD adherence); however, at 24 months, only 11% reported no gluten exposure. CD patients may be unable to consistently choose gluten-free foods based on product labeling. Explicit identification of gluten-free products may be helpful. Label reading ability appears stable over time. Further studies are needed to evaluate whether erroneous label reading or misleading labels are associated with persistent villous atrophy.

Prevalence of celiac disease in a large cohort of young patients with type 1 diabetes.

Serological screening for celiac disease (CD) allows the identification of individuals genetically predisposed, as type 1 diabetes mellitus (T1DM). However, the diagnosis is confirmed by intestinal biopsy. The aim was to determine the prevalence of immunoglobulin-A anti-tissue transglutaminase antibodies (IgA-tTG) and CD in a large cohort of young T1DM patients. Screening for CD was randomly conducted in 881 T1DM by IgA-tTG and total IgA. Individuals with positive antibodies were referred to endoscopy/duodenal biopsy. The age of the cohort at the screening was 14.3 ± 5.9 years and at T1DM onset was 7.9 ± 4.4 years. The prevalence of positive serology was 7.7%. Median IgA-tTG levels were 117.7 U/mL (interquartile range [IQR] 35.7-131.5 U/mL). Of the 62 duodenal biopsy, CD was diagnosed in 79.0%, yielding an overall prevalence of 5.6%. The mean age of CD patients was 15.6 ± 6.5 years and, at T1DM onset was 6.3 years (4.0-9.9 years). The modified Marsh-Oberhuber histological classification was 22.5% (3a), 36.7% (3b), and 40.8% (3c). In the biopsy-proven patients, T1DM onset occurred at slightly younger ages (6.3 vs 9.7 years, P = 0.1947), gastrointestinal (GI) manifestations, predominantly abdominal pain and distension, were more prevalent (71.4% vs 38.5%, P = 0.027) and higher IgA-tTG titers (128.0 vs 26.3 U/mL, P = 0.0003) were found than in those with negative-biopsies. Our results demonstrate the prevalence of 7.7% of IgA-tTG and 5.6% of CD in T1DM patients in South Brazil and, emphasize the importance of the screening in high-risk individuals. Furthermore, the presence of GI manifestations and higher IgA-tTG titers strongly suggest the diagnosis of CD.

Identifying True Celiac Disease and Wheat Allergy in the Era of Fashion Driven Gluten-Free Diets

Background: Diagnosing both celiac disease (CD) and wheat allergy (WA) might be challenging due to the increasingly popular gluten-free diets. Objectives: This study investigates the value of anti-tissue transglutaminase IgA (tTGIgA) and wheat-specific IgE (WIgE), and identifies clinical and serological features associated with CD and WA. Method: Serological markers of autoimmunity and allergy along with medical charts of patients assessed for tTGIgA and WIgE between 2010 and 2016 were evaluated. Results: During the last years, an increasing number of patients have been tested for tTGIgA, while the number of positive results decreased linearly. Among the 2,965 patients included, 128 patients showed at least once a positive tTGIgA. All patients with tTGIgA levels higher than the 12-fold upper normal limit had CD. The ratio of tTGIgA/total IgA did not perform better as a diagnostic test for CD compared to tTGIgA. tTGIgA and anti-nuclear antibodies were significantly associated. WA was only rarely investigated, particularly in adults. However, positive WIgE were found in nearly 50% of the cases. WIgE and tTGIgA values were negatively correlated. Conclusions: tTGIgA were increasingly tested, while the rate of positive results decreased in recent years, possibly reflecting the impact of current alimentary trends on clinical practice. Associated autoimmune disease was frequently found in CD. High levels of tTGIgA accurately predicted CD diagnosis. WA was rarely investigated and deserves more attention, in particular in children with atopic background. WA does not seem to be associated with CD.

Beneficial effects of gluten free diet on IgA tissue transglutaminase levels and various growth parameters in celiac disease patients.

Context:In the resource poor country like India it is difficult to get HLA screening and EMA testing in patients with celiac disease in small centres.Aims:To study the effect of gluten free diet on IgA tissue transglutaminase levels and various growth parameters in patients with celiac disease.Settings and Design:This was a prospective study conducted in the department of paediatrics of a tertiary referral hospital in north India in 3 stages viz. on presentation, after 3 months and 6 months of initial presentation.Materials and Methods:392 patients with symptoms suggestive of celiac disease were screened for IgA tTG levels more than 10 folds of upper limit of normal. 50 cases (who followed up for 6 months regularly) were enrolled in the study. Spectrum of various growth and clinical parameters were also studied. Statistical analysis used: Statistical analysis was performed by the SPSS version 20.0. Data were checked for normality before statistical analysis. p value less than 0.05 was considered statistically significant.Results:50 cases were enrolled in study. After initiation of gluten free diet, improvements were seen in various growth factors like height (12.71%) and weight (3.47 cm) after 6 months. Serum tTG(IgA) levels decreased to 94.88±55.35 U/mL from baseline level of 202±83.96 U/mL after 6 months.Conclusions:Gluten free diet has major role in improvement in growth parameters as well as anemia. So, early detection of celiac disease is an important step in prevention of morbidity associated with this chronic disease.

Prevalence of celiac disease in children with type 1 diabetes mellitus and the accuracy of serological tests

In children with type 1 diabetes mellitus (DM), prevalence of some autoimmune diseases like celiac disease (CD) has been increased. It is also reported that CD often can be asymptomatic and only serologically evident in patients with type 1 DM. In our study, we aimed to investigate the prevalence of asymptomatic CD and the specificity and sensitivity of anti-gliadin antibodies (AGA), anti-endomysium (EMA) and tissue transglutaminase (tTG) antibodies that used for diagnosis of CD in these patients. Anti-gliadin-IgA, AGA-IgG, EMA, tTG-IgA levels were evaluated. Small-intestine biopsies were applied to the children that parents were positive for at least one of AGA-IgA, AGA IgG, EMA and tTG-IgA. A total of 268 Type 1 DM children were included in the study. Of these sixty-four children who had at least one serological positive underwent small intestine biopsies and in five children (1.9%) CD was diagnosed. Anti-endomysium and tTG-IgA positivity were detected in all cases with Celiac disease, and sensitivity was 100% for both and 95% and 86% for specificity, respectively. The sensitivity and specificity of anti-endomysium and tTG-IgA antibodies were considered to be the most reliable indicator because of their higher specificity than other serological tests. Our results, which support current guidelines, suggest that children with Type 1 DM can be screened with tTG-IgA and EMA, which are the most sensitive and specific tests to detect asymptomatic CD in these patients.

Tests for Serum Transglutaminase and Endomysial Antibodies Do Not Detect Most Patients With Celiac Disease and Persistent Villous Atrophy on Gluten-free Diets: a Meta-analysis

Tests to measure serum endomysial antibodies (EMA) and antibodies to tissue transglutaminase (tTG) were developed to screen for celiac disease in patients consuming gluten. However, they are commonly used to monitor patients on a gluten-free diet (GFD). We conducted a meta-analysis to assess the sensitivity and specificity of tTG IgA and EMA IgA assays in identifying patients with celiac disease who have persistent villous atrophy despite a GFD. We searched PUBMED, EMBASE, BIOSIS, SCOPUS, clinicaltrials.gov, Science Citation Index, and Cochrane Library databases through November 2016. Inclusion criteria were studies of subjects with biopsy-confirmed celiac disease, follow-up biopsies, and measurement of serum antibodies on a GFD, biopsy performed on subjects regardless of symptoms, or antibody test results. Our analysis excluded subjects with refractory celiac disease, undergoing gluten challenge, or consuming a prescribed oats-containing GFD. Tests were considered to have positive or negative findings based on manufacturer cut-off values. Villous atrophy was defined as a Marsh 3 lesion or villous height:crypt depth ratio below 3.0. We constructed forest plots to determine the sensitivity and specificity of detection for individual studies. For the meta-analysis, a bivariate random effects model was used to jointly model sensitivity and specificity. Our search identified 5408 unique citations. Following review of abstracts, 442 articles were reviewed in detail. Only 26 studies (6 of tTG assays, 15 of EMA assays, and 5 of tTG and EMA assays) met our inclusion criteria. The most common reason studies were excluded from our analysis was inability to cross-tabulate histologic and serologic findings. The serum assays identified patients with persistent villous atrophy with high levels of specificity: 0.83 for the tTG IgA assay (95% CI, 0.79-0.87) and 0.91 for the EMA IgA assay (95% CI, 0.87-0.94). However, they detected villous atrophy with low levels of sensitivity: 0.50 for the tTG IgA assay (95% CI, 0.41-0.60) and 0.45 for the EMA IgA assay (95% CI, 0.34-0.57). The tests had similar levels of performance inpediatric and adult patients. In a meta-analysis of patients with biopsy-confirmed celiac disease undergoing follow-up biopsy on a GFD, we found that tests for serum tTG IgA and EMA IgA levels had low sensitivity (below 50%) in detection of persistent villous atrophy. We need more-accurate non-invasive markers of mucosal damage in children and adults with celiac disease who are following aGFD.