anti-tTG Levels Research Articles

Frequency of Celiac Disease and Spontaneous Normalization Rate of Celiac Serology in Children and Adolescent Patients with Type 1 Diabetes

Objective:The prevalence of celiac disease (CD) varies between 1% and 10% in patients with type 1 diabetes mellitus (T1DM). This study aimed to determine the frequency of spontaneous recovery of celiac serology and the biopsy-proven CD (BPCD) frequency in patients with T1DM.Methods:The data of 668 patients with available celiac serology tests from a total of 779 patients who were followed for the last 10 years with the diagnosis of T1DM were retrospectively evaluated.Results:Positive serology was detected in 103 out of 668 (15.4%) patients. There was spontaneous normalization in 24 (23.3%), fluctuation in 11 (10.7%) and permanently positive serology in 68 (66%). In 46 out of 53 (86.8%) patients with positive serology and biopsy, CD diagnosis was confirmed by biopsy (BPCD). The frequency of BPCD was 6.9%, and the serology in 76.1% was positive at the time of diagnosis of T1DM. The weight, height and body mass index-standard deviation score at diagnosis were lower in patients with BPCD compared to the group without CD. An anti-tissue transglutaminase-IgA (anti-TTG-IgA) level of 11.8 times the upper limit of normal was the most sensitive (93%) and specific (90%) cut-off for BPCD (area under the curve: 0.95; 95% confidence interval: 0.912-1; p<0.001).Conclusion:In our cohort, the frequency of positive serology for CD was 15.4%, while the rate of BPCD was 6.9%. The majority (97.8%) of cases were diagnosed within the first five years of T1DM. In 23.3% of cases, positive anti-TTG-IgA spontaneously resolved without a gluten-free diet (GFD). Therefore, serological follow-up instead of immediate duodenal biopsy or GFD therapy, particularly for patients with asymptomatic and mild anti-TTG IgA level, is warranted.

Prevalence of celiac disease in irritable bowel syndrome patients: A single centre experience from a large teaching hospital of Lahore, Pakistan

Background: Many studies have been conducted worldwide to evaluate the proportion of patients with Celiac disease (CD) in persons presenting with Irritable Bowel Syndrome (IBS), showing a positive association between the two diseases. However, reports from Pakistan remain scanty. This study aims to find out the prevalence of CD in patients presenting with IBS and to establish the correlation of both diseases.&#x0D; Patients and methods: It was a descriptive cross-sectional study conducted at Combined Military Hospital, Lahore (CMHL) from January 2018 till March 2019. Consecutive, nonprobability sampling was used to include 210 patients of both genders with the age range of 15-65 years fulfilling ROME IV criteria and were not previously diagnosed as CD or CKD or CLD. Demographic data was noted. Serum Anti tTG levels and Duodenal Biopsy from the second part was assessed to diagnose CD. CD was labeled if the disease was present on both serological and Histopathological reports. Data were analyzed by using SPSS version 20. Descriptive statistics were calculated and a Chi-square test was used to compare the outcome variables with P-value &lt; 0.05 as significant.&#x0D; Results: Of 210 enrolled patients, 113 (53, 8%) were male and 97 (46.2%) were female. The mean age of the patients was 28.40 ± 5.06 years. Eight patients (3.8%) were positive for Anti tTg and on histopathological findings suggestive of CD. Seven of 8 were less than 35 years old. Out of 8 positive patients, 6 (75%) were females. However, the p-value was found to be insignificant for age (0.549) and gender (0.096). On stratification with respect to duration of IBS, all 8 patients diagnosed with celiac disease were having symptoms of IBS for less than 12 months (100%) which was significant statistically (7.1% vs 0.0%; p=0.007).&#x0D; Conclusion: The frequency of CD was 3.8% among IBS patients. Considering this percentage of CD in IBS patients s, a high index of suspicion for CD in IBS patients is required,

Impact of Serological and Histological Factors on Neurological Manifestations in Children and Adults with Celiac Disease.

PurposeCeliac disease (CD) is a common autoimmune disease with extra-intestinal manifestations, including neurological disorders. There are few reports to assess various factors in increasing the chances of developing neurological disorders in CD, so we designed this study.MethodsAll patients with CD at any age who had been referred to the Celiac Clinic were evaluated for neurological problems. CD was defined as IgA anti-transglutaminase antibodies (anti-tTG) of 18 IU/mL or higher in serology and Marsh type I or more severe in histopathological evaluation. Logistic regression analysis was used to evaluate the impact of various independent variables on the neurological manifestations.ResultsA total of 540 patients enrolled in this study. A 360 (66.7%) of patients were children. A 64.8% and 35.2% were female and male, respectively. Overall, 34.1% of patients had neurological manifestation, including headache, neuropathy, epilepsy, and ataxia. The odds of developing neurological manifestations in children were significantly lower than in adults (odds ratio [OR], 0.66; 95% confidence interval [CI], 0.45–0.96; p=0.03) and in patients with gastrointestinal (GI) symptoms significantly higher than in the group without GI manifestations (OR, 1.77; 95% CI, 1.18–2.63; p=0.005). Other variables, including Marsh classification (OR, 0.44; 95% CI, 0.18–1.11; p=0.08) and anti-tTG levels (OR, 1.00; 95% CI, 0.999–1.001; p=0.59) did not significantly increase the chances of developing neurological disorders.ConclusionOur study showed that increasing age and the presence of GI symptoms, but not serological and histological findings, could increase the chances of developing neurological diseases in CD patients.

Routine Multiple Duodenal Biopsy during Endoscopy of Dyspeptic Patients Seems Unnecessary for Screening of Celiac Disease.

Introduction Celiac disease (CD) is a chronic and common cause of dyspepsia with a rising prevalence worldwide. This study is aimed at investigating the prevalence of CD in dyspeptic patients based on serology and biopsy, determining the associated factors, and assessing the necessity of regular duodenal biopsies from normal mucosa in diagnosis of CD among dyspeptic patients. Methods This cross-sectional study was performed on 530 adult dyspeptic patients who underwent gastroduodenoscopy in Imam Reza hospital, Mashhad, during 2016-2018. Demographic characteristics, clinical data, and laboratory analyses were extracted from hospital records. CD was diagnosed based on intestinal biopsy and serum antitissue transglutaminase (anti-TTG) levels. Mucosal lesions were classified according to the modified Marsh classification. Data were analyzed in SPSS with P < 0.05 being considered significant. Results Overall, 163 males (30.8%) and 367 females (69.2%) with an average age of 46.38 ± 15.54 years were studied. High anti-TTG levels were seen in 36 (6.8%) patients, and duodenal pathologies were seen in 23 (4.5%) patients. Fifteen (2.8%) were diagnosed with CD based on both serology and biopsy. Bloating was the most common type of dyspepsia in CD patients (7, 46.7%), followed by epigastric pain (6, 40%), and postprandial fullness (2, 13.3%). Two CD patients (13.3%) reported a positive family history for CD. Logistic regression model showed that iron deficiency anemia (IDA), anti-TTG level, and Helicobacter pylori infection were predictors of histological changes of CD, whereas IDA was the only independent predictor of CD in dyspeptic patients (OR = 17.65, 95%CI = 1.53‐202.52, and P = 0.021). Conclusion CD is prevalent in dyspeptic patients, but routine biopsy from normal-appearing duodenal mucosa is not recommended for all patients. Serological studies, complete history, and careful endoscopic evaluation may provide better cost-effective clinical solutions to improve the diagnostic yield of celiac disease in dyspeptic patients.

Celiac disease can be predicted by high levels of tissue transglutaminase antibodies in children and adolescents with type 1 diabetes.

ObjectivesChildren with type 1 diabetes (T1D) are not included in guidelines regarding diagnosis criteria for celiac disease (CD) without a diagnostic biopsy, due to lack of data. We explored whether tissue transglutaminase antibodies (anti‐tTG) that were ≥ 10 times the upper limit of normal (10× ULN) predicted CD in T1D.MethodsData from the Swedish prospective Better Diabetes Diagnosis study was used, and 2035 children and adolescents with T1D diagnosed between 2005–2010 were included. Of these, 32 had been diagnosed with CD before T1D. The children without CD were repeatedly screened for CD using anti‐tTG antibodies of immunoglobulin type A. In addition, their human leukocyte antigen (HLA) were genotyped. All children with positive anti‐tTG were advised to undergo biopsy. Biopsies were performed on 119 children and graded using the Marsh‐Oberhüber classification.ResultsAll of the 60 children with anti‐tTG ≥10x ULN had CD verified by biopsies. The degree of mucosal damage correlated with anti‐tTG levels. Among 2003 screened children, 6.9% had positive anti‐tTG and 5.6% were confirmed CD. The overall CD prevalence, when including the 32 children with CD before T1D, was 7.0% (145/2035). All but one of the children diagnosed with CD had HLA‐DQ2 and/or DQ8.ConclusionsAs all screened children and adolescents with T1D with tissue transglutaminase antibodies above 10 times the positive value 10x ULN had CD, we propose that the guidelines for diagnosing CD in screened children, when biopsies can be omitted, should also apply to children and adolescents with T1D as a noninvasive method.

Positive tissue transglutaminase antibodies with negative endomysial antibodies: Unresolved issues in diagnosing celiac disease

BackgroundThe serological screening for celiac disease (CD) is currently based on the detection of anti-transglutaminase (tTG) IgA antibodies, subsequently confirmed by positive endomysial antibodies (EMA). When an anti-tTG IgA positive/EMA IgA negative result occurs, it can be due either to the lower sensitivity of the EMA test or to the lower specificity of the anti-tTG test. This study aimed at verifying how variation in analytical specificity among different anti-tTG methods could account for this discrepancy. MethodsA total of 130 consecutive anti-tTG IgA positive/EMA negative samples were collected from the local screening routine and tested using five anti-tTG IgA commercial assays: two chemiluminescence methods, one fluoroimmunoenzymatic method, one immunoenzymatic method and one multiplex flow immunoassay method. ResultsTwenty three/130 (17.7%) patients were diagnosed with CD. In the other 107 cases a diagnosis of CD was not confirmed. The overall agreement among the five anti-tTG methods ranged from 28.5% to 77.7%. CD condition was more likely linked to the positivity of more than one anti-tTG IgA assay (monopositive = 2.5%, positive with ≥ three methods = 29.5%; p = 0.0004), but it was not related to anti-tTG IgA antibody levels (either positive or borderline; p = 0.5). ConclusionsPatients with positive anti-tTG/negative EMA have a low probability of being affected by CD. Given the high variability among methods to measure anti-tTG IgA antibodies, anti-tTG-positive/EMA-negative result must be considered with extreme caution. It is advisable that the laboratory report comments on any discordant results, suggesting to consider the data in the proper clinical context and to refer the patient to a CD reference center for prolonged follow up.

Measures of gluten-related reactivity in children with autism spectrum disorders in the absence of overt gastrointestinal symptoms: a pilot study from the United Arab Emirates.

ObjectivesThe aetiology of autism spectrum disorder (ASD) is multifactorial, sometimes genetic, and may be associated with abnormal immunological responses to peptides from proteins such as gluten. These peptides may cross the blood-brain barrier and affect neurotransmission, resulting in behavioural symptoms consistent with ASD. The aim of this study was to screen for markers of gluten-related immune reactivity in the absence of overt gastrointestinal symptoms in patients with ASD in the United Arab Emirates, a country associated with a high prevalence of ASD but lacking this type of research.MethodsPatients diagnosed with ASD (using Diagnostic and Statistical Manual of Mental Disorders-IV-based criteria and Autism Diagnostic Observational Schedules) were compared with controls, regarding anti-tissue transglutaminase (tTG) immunoglobulin (Ig) A and anti-deamidated gliadin peptide (DGP) IgA levels.ResultsSixty-six patients with ASD and 101 controls were included. Patients with ASD showed statistically significant lower anti-DGP IgA levels, but no significant difference in anti-tTG IgA levels, versus healthy controls. Correlations between immunological data and clinical symptoms were synergistic, but not statistically significant.ConclusionASD may be associated with reduced levels of anti-DGP IgA.

A Cross Sectional Survey on Tissue Transglutaminase Auto-Antibodies in Patients with Pulmonary and Extra Pulmonary Tuberculosis

Background: Mycobacterium tuberculosis (TB) is a widespread life-threatening infection worldwide. There is an uncertainty in the association between the emergence of autoimmune antibodies and TB. Objectives: We hereby aimed to screen anti-tissue transglutaminase (anti-tTG) IgA in patients with TB in an Iranian population. Methods: This was a cross sectional study conducted on smear positive TB patients admitted to the Respiratory Diseases Management Center of the city of Zabol, Sistan and Baluchestan Province of Iran during 2017 - 2018. Anti-tTG IgA level was determined using an ELISA kit (Pars Azmoun, Iran). Statistical analyses were performed in SPSS 19 software. Results: Overall, 162 patients were evaluated. Females and males constituted 87 (53.7%) and 75 (46.3%) of the patients respectively. The mean age was 51.7 ± 22.3 years (range of 1 - 83). Afghan patients constituted 16 (9.9%) and the remaining were Iranians. The therapy course was successfully completed in 78 (48.1%) patients, and 67 (41.4%) improved following treatments. Overall, 5 patients had active TB with 2 drug-resistant cases. Pulmonary tuberculosis was diagnosed in 127 (78.4%) while 35 (21.6%) had extra-pulmonary disease. The mean titer of anti-tTG IgA was 22.59 ± 107.7 (range of 0.8 - 940). Overall, 19 (11.9%) of the patients showed elevated levels of the antibody. There was no significant association between anti-tTG IgA titer with neither demographic nor clinical variables. Conclusions: Although anti-tTG IgA antibody test was positive in a relatively high ratio of our patients with TB, the clinical implications of this phenomenon were not significant.

A109 CELIAC DISEASE IS A RARE CAUSE OF BENIGN DUODENAL STRICTURE

Abstract Background Benign duodenal stricture is an uncommon problem encountered by gastroenterologists. The most common cause is peptic ulcer disease (PUD). With the diagnosis and eradication of H. Pylori, early diagnosis of PUD and the use of PPIs to treat upper gastrointestinal inflammation, the incidence of benign duodenal stricture has dramatically decreased. Patients with duodenal stricture may present with early satiety, nausea, vomiting and weight loss. We present the case of a man with a refractory web-like stricture in the second part of the duodenum (D2) caused by Celiac disease. Aims To describe a rare endoscopic finding in a patient with Celiac disease Methods Case report with literature review Results We present a case of a 64 year old male was referred for consideration of duodenal stenting of a refractory stricture in the second part of the duodenum D2. The patient had a 1 year history of abdominal pain, early satiety and weight loss (10 lbs). He also reported intermittent episodes of diarrhea. Investigations included a CT scan of the abdomen which showed a stricture at the level of proximal D2 described as a “duodenal band”. Previous attempts at balloon dilation had not resulted in prolonged symptomatic or endoscopic improvement. Testing for H. Pylori was negative and he did not use NSAIDs. Upper endoscopy was performed to assess the stricture prior to consideration of stenting. This showed a tight web-like stricture in proximal D2. The stricture was balloon dilated up to 16.5 mm, enabling the endoscope to pass beyond it. The mucosa in D2 was atrophic with flattening of the folds and scalloping. There was no inflammation seen. Biopsies from D2 revealed moderate villous blunting and intraepithelial lymphocytosis. Celiac serology testing was abnormal, with an anti-tTG Ab level of 32 RU/ml which confirmed the diagnosis of Celiac disease. The balloon dilation and gluten-free diet resulted in resolution of his symptoms. Follow up endoscopy revealed normalization of his duodenal folds and biopsies. In addition, anti-tTG Ab level was normalized. Although stricture improved with prolonged patency, he still has mild recurrence of his stricture requiring balloon dilation on an annual basis. Conclusions This case describes a very uncommon complication of Celiac disease. The likely pathophysiology involves inflammation and potentially ulceration from Celiac disease, resulting in a benign stricture. There have been a few case reports describing duodenal strictures as a complication of Celiac disease. Treatment involves a gluten-free diet and endoscopic therapy. More severe cases of obstruction would likely require surgical intervention. In our case, the gluten-free diet and balloon dilation were successful and duodenal stenting was not necessary. Given the possibility of Celiac disease as a cause of duodenal stricture, it would be reasonable to biopsy D2 and check anti-tTG Ab in cases of duodenal stricture. Funding Agencies None

Can a Synbiotic Supplementation Contribute to Decreasing Anti-Tissue Transglutaminase Levels in Children with Potential Celiac Disease?

PurposeSynbiotics 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.MethodsEighty-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.ResultsThe 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).ConclusionIt may be speculated that a synbiotic supplementation can contribute to decreasing anti-tTG levels in children with potential CD.

Correlation of Ultrasonography Parameters with Tissue Transglutaminase Antibody Assay in the Diagnosis of Childhood Celiac Disease

Objective: The present study aimed to evaluate the potential benefits of ultrasonographic (USG) assessment in the diagnostic workup of children suspected of having celiac disease and its correlation with tissue transglutaminase (TTG) antibody assay. Materials and methods: A retro-prospective study, consisting 30 children with biopsy proven celiac disease diagnosis, was conducted. The tissue transglutaminase (tTG) assay was done on all the children, and further the children were subclassified based on the tTG titer values. The transabdominal sonography using convex (3-5 MHz) and linear (7-12 MHz) ultrasound probes was carried on the subjects, assessing the bowel lumen dimeter, bowel wall thickness, abnormal rugal folds count, presence of perihepatic fluid, fatty hepatic changes and mesenteric lymphadenopathy. Routine abdominal sonography was also carried out to complete the detailed evaluation of the abdomen. The sonographic bowel findings and the different classes of the tTG titers were correlated. Results: The median (IQR) age at onset of symptoms and at diagnosis was 6 (4-9) years. The median (IQR) value of blood tissue transglutaminase level (tTG) was 535 U/mL (63-7100), and most of the children belonged to class A (n=18, 60%) subclassification followed by class C (n=7, 23.3%) and class B (n=5, 16.6%). On sonological evaluation, the bowel abnormalities including bowel thickening was seen in 8 (26.6%) of the children, followed by the reduced jejunal folds and transient intussusception in the same frequency (n=5, 16.6%) and, hyper-peristalsis in 4 (13.3%) children. No dilated bowel loops were seen. Extra-intestinal observations like fatty liver changes, mesenteric lymphadenopathy, and peritoneal free fluid were noted in 23 (76.6%), 6 (20%), and 4 (13.3%) of the children respectively. Conclusion: Ultrasound is the most widely used first imaging tool in the evaluation of abdominal ailments. Multiple small bowel abnormalities are found in the celiac patients, which may vary according to the study population’s demographic and clinical features. More than half of the children with celiac disease showed small bowel abnormalities, and small bowel thickening, if present, may vary with the anti-tTg titer level. Multicentric and large size sample studies are required to accurately assess the association of serological antibodies titers with the bowel wall abnormality.

Frequency of autoimmune thyroiditis in children with Celiac disease and effect of gluten free diet.

Objective:To determine the frequency of autoimmune thyroiditis in children with Celiac disease and the effect of gluten free diet on autoimmune thyroiditis.Methods:We enrolled 100 patients, age 1-12 years of either gender diagnosed as Celiac disease (CD) in this prospective observational study in the Department of Pediatric Medicine, from 1st January 2018 to 30th June 2019. Diagnosis of autoimmune thyroiditis was made if anti–thyroperoxidase >35 iu/ml or anti–thyroglobulin >20 iu/ml at diagnosis of CD and then at one year on gluten free diet (GFD) in all cases. Children with repeat anti-tTG levels > 10 times upper limit normal at 6-months after enrollment were labelled as non-compliant to GFD. Descriptive statistics were used to analyze the data.Results:Mean age of the participants was 5.94±3.16 years and 53% were females. Fourteen cases of autoimmune thyroiditis were detected at enrollment and six (7%, n/N = 6/86) were later diagnosed on follow-up who were initially negative. Seven hypothyroid cases among the autoimmune thyroiditis were treated with thyroxine and became euthyroid on follow-up testing. Compliance to GFD was 52%. Autoimmune thyroiditis improved on gluten free diet in four cases (28.6%). Of the six euthyroid cases at diagnosis three cases became hypothyroid and all were non-compliant.Conclusion:Frequency of autoimmune thyroiditis was 20% over a follow-up period of one year. Good compliance with the GFD has some effect on improving autoimmune thyroiditis and maintaining euthyroid status of CD patients.

2604 Celiac Disease: No Longer a Diagnosis of Exclusivity

INTRODUCTION: Celiac disease (CD) is a chronic autoimmune enteropathy that occurs in genetically susceptible individuals when exposed to gluten proteins. In the past, CD was thought to be exclusive to Caucasians of European descent. With the advent of serological screening tests, CD has become increasingly recognized in other ethnic populations around the world. CASE DESCRIPTION/METHODS: A 56-year-old female of Indian descent was evaluated for chronic epigastric abdominal pain. The pain did not radiate and worsened with certain movements and spicy foods. She also reported an occasional acidic taste suggestive of reflux. Medical history included arthritis, hyperlipidemia, and a cholecystectomy. A colonoscopy performed two years ago was unremarkable. She underwent an EGD which demonstrated a normal esophagus, mild antral gastritis, and flattening of duodenal villi. Biopsies were obtained and an anti-tissue transglutaminase (anti-tTG) IgA level was ordered for suspicion of CD. Histology of the duodenal mucosa revealed moderate villous atrophy and increased intraepithelial lymphocytes. Anti-tTG IgA levels were elevated at 39 U/mL (normal 0–3 U/mL). H. pylori testing was negative. CD was diagnosed based on the histological findings and positive serology. The patient was instructed to begin a gluten-free diet (GFD) and referred to a medical nutritionist for further assistance. After starting a GFD, she reported significant symptomatic improvement. DISCUSSION: Few population studies in the past have looked at the prevalence of CD in non-Caucasian ethnic groups where the disease may have been underdiagnosed. Several recent studies suggest that gluten intolerance is more common than previously estimated in certain populations. Cataldo et al reported that 26–49% of Indian children presenting to tertiary care hospitals with chronic diarrhea had been diagnosed with CD.1 And a review by Yachha et al of an earlier study from the UK found 20 of 106 CD patients to be of South Asian origin.2 This case highlights the changing global paradigm of CD prevalence and provides valuable insight for clinicians in Western countries serving diverse immigrant populations. In conclusion, we recommend that physicians assess for CD without racial bias if clinical suspicion warrants an evaluation.

Correlation of Serum Tissue Transglutaminase Antibody Levels and Marsh Grading of Duodenal Biopsy in Patients of Celiac Disease

Background: Celiac disease (CD) is a chronic small intestinal immune-mediated enteropathy precipitated in genetically predisposed individuals by ingestion of wheat gluten and related proteins of barley and rye. It is an under-diagnosed gluten-sensitive enteropathy, usually presenting with atypical/extra-intestinal features. Duodenal biopsy is considered as the gold standard in the diagnosis of CD. Serum anti tissue transglutaminase (anti-tTG) antibodies is auto antibodies directed against tissue transglutaminase (tTG) enzyme. Aims and objective: The aim of the study is to find out the prevalence of CD among clinically suspected cases of malabsorption, to assess the correlation of anti-tTG levels with modified Marsh grading of duodenal biopsy, to find out sensitivity, specificity and predictive values of anti-tTG test and to calculate the cut off values of anti-tTG diagnostic of high grade CD. Methodology: The present study included 118 clinically suspected patients of malabsorption in which both duodenal biopsy and anti-tTG test was done. The mucosal damage graded according to the modified Marsh grading and anti-tTG tests were done in serum using ELISA kit. Results: The prevalence of CD among clinically suspected cases of malabsorption was 12.7%. The incidence was highest in middle aged male patients. The most common clinical symptom was chronic diarrhea and commonest presenting sign was anemia. Anti-tTG levels were found to be proportionately increasing with the severity of CD and showed a positive correlation(r=0.433). Patients with anemia and chronic diarrhea showed statistically significant (p value=0.0242 and 0.0089 respectively) mean anti-tTG levels in Celiac patients in relation to non-Celiac patients. Although the mean levels of anti-tTG was 6.3 times higher than baseline in grade 3 disease, the ROC analysis showed that anti-tTG in isolation had no significance in exactly grading the disease (AUC=0.30). Conclusion: Positive correlation was found between anti-tTG levels and modified Marsh grading. Anti-tTG showed proportionate increase with severity of duodenal damage. Anti-tTG test showed low sensitivity (42.86%) and high specificity (84.34%). Hence it is not a reliable tool in isolation to screen CD but should be used in combination with duodenal biopsy. It can be used to assess the severity of CD and for follow up.

Role of anti-tissue transglutaminase IgA+IgG antibodies in detection of potential celiac disease in patients with type 1 diabetes.

Background & objectives:Celiac disease (CD) can exist in various forms in type 1 diabetes (T1D) patients and can remain undetected, leading to severe complications. This study was aimed to evaluate five commercially available anti-tissue transglutaminase (tTG) ELISA kits with distinct formats for the detection of CD and potential CD in T1D patients. Clinical and demographic profiles of the patients with different disease subsets were also studied.Methods:Fifty T1D patients with classical and non-classical symptoms of CD and 100 T1D patients without any symptoms of CD were included in this study. Anti-tTG autoantibody levels were estimated by five ELISA kits followed by histological examination of duodenal biopsy. HLA DQ2-DQ8 and DRB1-DQB1 typing was done, and serum levels for transforming growth factor (TGF)-β1 were also estimated.Results:Assay format detecting anti-tTG IgA antibodies against recombinant antigens along with neopeptides of gliadin was most efficient in the detection of CD in symptomatic patients, and assay format detecting IgA+IgG helped in the detection of potential CD in asymptomatic T1D patients. These findings were supported by histological examination and human leucocyte antigen analysis. Patients with potential CD were found to have markedly deranged glycaemic control parameters and also had significantly raised serum levels of TGF-β1, (P<0.05) compared to T1D patients.Interpretation & conclusions:Potential CD can be frequently seen in T1D patients. This can be attributed to the dietary patterns prevalent in the subcontinent and the genetic basis of the disease. Anti-tTG IgA+IgG antibodies can be useful in the detection of these potential CD cases in T1D patients. Early intervention with gluten-free diet can be considered in these patients for better disease management.

Anti-tissue transglutaminase antibodies not related to gluten intake

Abstract Introduction Anti-tissue transglutaminase antibodies (tTG) have high specificity for coeliac disease (CD). However, positive anti-tTG antibodies have been described in non-coeliac patients. Aim To assess positive anti-tTG antibodies not related to gluten intake. Patients and methods Retrospective review and follow up conducted on patients with suspected CD (increase anti-tTG levels and gastrointestinal symptoms) but with atypical serology results, positive anti-tTG with gluten free diet and a decrease in anti-tTG levels despite gluten intake. Results A total of 9 cases were reviewed in which 5 cases had Marsh 3 involvement in the initial biopsy, and were diagnosed with CD (Group A). They began a gluten free diet and also a cow's milk protein (CMP) free diet because of their nutritional status. When CMP was re-introduced, anti-tTG increased, and returned to normal after the CMP was withdrawn again. The other 4 patients had a normal initial biopsy (Group B). Gluten was not removed from their diet, but they started a CMP free diet because a non IgE mediated CMP allergy was suspected. Symptoms disappeared, and anti-tTG was normal after CMP free diet with gluten intake. All the patients had susceptibility haplotype HLA DQ2/DQ8. Conclusions CMP ingestion after an exclusion diet can induce an increase in anti-tTG in some coeliac subjects. CMP can produce this immune response if there were no gluten transgressions. This response has also been observed in non-IgE mediated CMP allergy patients with the susceptibility haplotype HLA DQ2/DQ8.

Relationships between Clinical Presentation, Serology, Histology, and Duodenal Deposits of Tissue Transglutaminase Antibodies in Pediatric Celiac Disease

Background: The clinical, histological, and serological spectrum of celiac disease (CD) vary widely. We aimed to examine relationships between symptoms, serum anti-tissue transglutaminase antibodies (tTG) levels, mucosal damage, and mucosal anti-tTG deposits in pediatric CD. Methods: A retrospective single-center, cohort study of children referred for endoscopy with suspected CD during 2011–2014. We retrieved the clinical data, blindly reviewed duodenal biopsies, and performed immunohistochemical staining for anti-tTG deposits. Patients were classified as monosymptomatic or polysymptomatic. Mucosal anti-tTG deposits were classified according to the location of deposits, dominant intensity, maximal intensity, and percentage of stained area. Results: Of 252 patients with confirmed CD, complete data were available for 100: 37 males in the age range 1.3–16.7 with median 4.0 years. Monosymptomatic patients (n = 54) presented at an older age than polysymptomatic patients (1.3–15.5, median 8.1 vs. 1.3–16.7, median 6.3 years, p = 0.026). Marsh 2–3c was more prevalent in polysymptomatic patients (93 vs. 78%, p = 0.028). The intensity of mucosal anti-tTG deposits correlated with serum anti-tTG levels but not with the clinical presentation. Conclusions: Multiple symptoms and high serum anti-tTG antibody levels correlated with mucosal damage in children with CD. The role of immunohistochemical staining for intestinal anti-tTG mucosal deposits in the diagnosis of borderline CD is not yet established.

Elevated anti-tissue transglutaminase antibodies in children newly diagnosed with type 1 diabetes do not always indicate coeliac disease.

Elevated levels of anti-tissue transglutaminase (anti-tTG) antibody may spontaneously normalise in children with newly diagnosed type 1 diabetes, even if they eat gluten. The prevalence of this phenomenon and predictors of a subsequent coeliac disease (CD) diagnosis were determined. The medical records of children diagnosed with type 1 diabetes at Ha'Emek Medical Centre, Israel, from 2007 to 2015, were retrospectively reviewed for elevated anti-tTG antibody levels. Demographic, clinical, laboratory and histological findings were compared between CD patients and those with transient coeliac serology. Of 425 patients with new onset type 1 diabetes, 34 (8%) had elevated anti-tTG antibodies: CD was diagnosed in 14, anti-tTG normalisation occurred in 13 and duodenal biopsies did not suggest CD in seven without anti-tTG antibody normalisation. Protective factors for a subsequent CD diagnosis were older age (p = 0.009) and mildly elevated anti-tTG antibody levels at the time of the type 1 diabetes diagnosis (p = 0.007), and decreased anti-tTG levels within six months of diagnosis (p = 0.03). Serological follow-up of a diet containing gluten is recommended for children who have newly diagnosed type 1 diabetes and slightly elevated anti-tTG antibodies with no symptoms that suggest CD.

Is it Celiac Disease or CVID-Associated “Celiac-Like Disease”?

Common Variable Immunodeficiency (CVID) is the most common primary immunodeficiency in adults. Gastrointestinal (GI) symptoms are common in CVID patients, and up to 50% of patients have chronic diarrhea with malabsorption. CVID is commonly associated with intestinal villous atrophy mimicking Celiac Disease (CD). The prevalence of true CD in CVID remains unknown. We present a case of gluten-free diet (GFD) responsive CD in a patient with CVID. A 67 year old Caucasian female with long standing history of CVID on IgG replacement therapy, chronic kidney disease, and severe iron deficiency presented for evaluation of persistent nausea, anorexia, weight loss and non-healing chronic leg ulcer. She underwent EGD after initial anti tissue transglutaminase (anti-TTG) was found to be 17 U/mL, which showed marked villous blunting and mild lymphocytic infiltration with inflammatory pathology. Enteral access was obtained for nutritional supplementation in a setting of ongoing weight loss. An EGD 1 month after high fidelity enteral GFD showed resolution of inflammatory changes and improvement in villous blunting. (Table 1) The ensuing 3 months of strict diet adherence resulted in removal of the feeding tube with resolution of anorexia and nausea, as well as a 35 pound weight gain with return to healthy baseline weight. A dramatic improvement in her chronic leg wound was observed that had previously been resistant to all therapies. Anti-TTG levels at 4 month mark improved to 8 U/mL. Common variable immunodeficiency (CVID) with an estimated prevalence of 1/100,000 to 1/50,000 is the most common symptomatic primary antibody deficient syndrome. Up to 50% of CVID patients have chronic diarrhea with malabsorption. CVID is commonly associated with intestinal villous atrophy mimicking Celiac Disease (CD). Due to unreliable antibody testing and inconsistent response to GFD making a diagnosis of CD in CVID remains a challenge. Based on a few recent studies, the only criterion to confirm CD in CVID population is histological response to GFD. Our patient had significant improvement in symptoms and showed a histological response with GFD. CVID and CD can co-exist, hence a high level of clinical suspicion is warranted to diagnose CD in the CVID population.Table: Table. Sequential Duodenal Bulb Biopsies

The Relationship Between The Type 1 Diabetes And Celiac Disease: A Study Based On Anti Tissue Transglutaminase Antibodies And Anti-Glidine Antibodies Screening

Background: The present investigation aims to study the prevalence rate and clinical characteristics of celiac disease(CD)among Iraqi children with type1 diabetes mellitus using a combination of the most sensitive and specific screening serologic tests anti-tissue transglutaminase antibodies IgA,IgG(tTG)and anti-gliaden antibodies IgA,IgG(AGA) and to determine the lower cut-off value of anti-tTG and anti-AGA level that best predicts celiac disease in patient with type1 diabetes. Materials: Two patient groups have investigated (each to NO =30) in this study one with celiac disease and the other with type1 diabetes mellitus compared to third group of apparently healthy control group of 20 individuals. patient with positive anti-tTG titer and AGA titer (&gt;18 U/ml) and patient with equivocal of anti-tTG and AGA titers(12–18 U/ml) and negative titers (&lt;18 U/ml ) Results: The median calculation of Anti-gliadin IgA (U\ml) were ;1.6 ,6.15 and 27.4 among healthy group ,type1 diabetes mellitus, and celiac disease patient respectively. An interesting ROC values (AUC 0.949-1.000) for this auto-antibodies as a perfect test in this aspect. In the same context, the IgG ,class of this auto-antibody occurred in median concentration of 3.05, 5.7 , and 21.85 among the three groups ,respectively. It significantly differed among this group and as compared to each other's. For anti-tissue transglutamenase assays ,Both IgA and IgG were provided with significant differentiation tools when compared among the three studied groups both classes provided had high ROC (0.947- 1.000). Conclusion: From the result of this study, we concluded the overlapping auto-antibodies profile celiac disease and type1 diabetes mellitus.