IgA Anti-tissue Transglutaminase Research Articles

A Dedicated Celiac Disease Program Improves Celiac Quality Care Metrics and Short-Term Outcomes in Real Life

Background and AimsDedicated multidisciplinary programs in gastroenterology are emerging with the goal to improve care. There is little information about the effects of a celiac disease program on disease-related quality care metrics and outcomes. We aimed to compare quality care metrics, symptom resolution, and serological response among patients diagnosed and treated in a celiac disease program with a standard of care cohort.MethodsWe performed a retrospective cohort study with adult celiac disease patients. We divided patients into two groups: celiac disease patients treated in our program and those treated by gastroenterologists not affiliated with the program (standard of care). We abstracted data from electronical medical records and compared frequency at which guideline-driven quality care metrics were obtained, assessed symptom resolution, and serological response based on IgA anti-tissue transglutaminase levels.ResultsWe included 340 patients, 120 in the celiac disease program (89 women) and 220 (166 women) in the standard of care. Frequency of quality care metrics implementation in program patients was significantly greater for all variables (p < 0.0005). Diarrhea resolved in 38/46 (82.6%) in the CD program and 63/98 (64.2%) in the standard of care after starting a gluten-free diet (p = .025); bloating also resolved significantly more often in the former (26/34) than the latter (31/58; p = 0.03). Otherwise, there were no significant differences in resolution of clinical symptoms or serological response.ConclusionA celiac disease program improves celiac-related quality care metrics and may improve outcomes such as diarrhea resolution compared to standard of care.

A69 EXPANDED ROLE OF THE DIETITIAN IN THE CLINICAL MANAGEMENT OF PATIENTS WITH CELIAC DISEASE

Abstract Background The only available treatment for Celiac Disease (CeD) is adhering to a strict gluten-free diet (GFD). However, a GFD has been associated with multiple nutrient imbalance and deficiencies, which are often under-recognized and remain untreated. Aims To identify the reasons for referral to a registered dietitian (RD) and RD-recommended dietary interventions for patients with CeD attending a specialised Adult Celiac Disease Clinic. Methods We conducted a retrospective chart review using nutrition assessment forms completed by the RD between November 2021 and May 2022. CeD diagnosis was performed through specific serology (anti-tissue transglutaminase IgA and anti-deamidated gliadin peptide IgG) and confirmed by duodenal biopsies demonstrating villous atrophy. We collected data on demographics, diagnosis date, nutritional status (BMI), micronutrients measured in serum, gastrointestinal (GI) symptoms, reason for consult, and the recommendations made by the RD. Data was collected in RedCap (v. 11.1, 2021, US) and expressed as both a proportion and Median (IQR). Results A total of 136 visits from 102 patients were included in the analysis. Of them, 77 were female (75.5%) with a mean age of 40.3 yrs (+/- 16.0). The median year of CeD diagnosis was 4 (IQR= 6) from 2002-2022. Patients reported various symptoms including bloating (50.9%), abdominal pain (34.3%), and constipation (23.5%). 56% of patients were overweight or obese (BMI ampersand:003E25), and 4.9% were undernourished (BMIampersand:003C18). The most common nutrient deficiencies were ferritin below 30 ng/mL (58.8%), zinc below 9.4 µmol/L (23.5%), and suboptimal levels of vitamin D (38.2%). The most common reasons for referral to the RD were to assess GFD adherence (44.1%), dietary management of GI symptoms (30.4%) and nutritional optimization (24.5%). We identified 18 different interventions recommended by the RD, the most common being how to prevent gluten cross-contamination (58.8%), tips for dining out (43.1%), GF diet education (32.4%), and increasing fibre intake (30.4%). The most common reasons for follow up visits (n=34) included dietary management of GI symptoms (60.9%) and GFD adherence (43.5%). Conclusions Patients with CeD face multiple nutritional challenges associated with following a GFD, and a number of GI symptoms. Although the GFD is the only available treatment, this review identifies the need for multiple individualized dietary interventions, which require and encourage the inclusion of a specialized RD to ensure personalized, effective care and support in the management of CeD. Funding Agencies None

Prevalence of celiac-related antibodies and its impact on metabolic control in Egyptian children with type 1 diabetes mellitus.

The simultaneous presence of celiac disease and type 1 diabetes (T1DM) is coupled with more hazards of comorbidities and complications. This current study aimed to screen for celiac disease in Egyptian children with type 1 diabetes and evaluate its impact on glycemic control. A cross-sectional study was verified with 200 Egyptian children diagnosed with T1DM and having a diabetic duration of less than five years. Testing for anti-tissue transglutaminase IgA (tTG-IgA), anti-tissue transglutaminase IgG (tTG-IgG), anti-Endomysial IgA (EMA), and Hb A1c levels were done. The serological screening revealed that 11 cases (5.5%) tested positive; 8 children with T1DM (4.0%) showed tTG-IgA antibodies ≥ 10 times the upper limit of normal (ULN) with at least one symptom; and 3 cases (1.5%) had levels between 20 and 50 IU/ml (considering a cut-off point of 10 U/ML for positive results). Intestinal biopsy was performed for these three cases, with one case detected to have subtotal villous atrophy, resulting in an overall prevalence of celiac disease in T1DM as 4.5%. Children with positive screening exhibited a higher insulin dose, a higher HbA1c, an increased frequency of hypoglycemic attacks, and recurrent DKA compared to negative cases. A negative correlation was detected between tTG-IgA antibodies with height Z score and hemoglobin level, while a positive correlation was found between tTG-IgA antibodies and HbA1c level. Undiagnosed celiac disease in children with T1DM negatively impacted metabolic control and affected their general health.

Prevalence of celiac disease in Moroccan children with type 1 diabetes mellitus: A 16-year cross-sectional study.

There is limited data available regarding the prevalence of celiac disease (CD) among children with type 1 diabetes mellitus (T1DM) in Arab countries and the Middle East. This cross-sectional study has been designed to explore the prevalence of CD specifically within the population of Moroccan children and adolescents diagnosed with type 1 diabetes mellitus (T1DM). This is a cross-sectional study of patients who underwent regular follow-up for T1DM at the Pediatric Endocrinology Unit, Abderrahim Harouchi Children's University Hospital in Casablanca, over a 16-year period from 2004 to 2020. Patients were screened for CD by measuring anti-tissue transglutaminase IgA, and those with positive antibodies underwent endoscopy assessment. All 550 patients regularly followed up with TIDM were screened for CD. Fifty-five (33 girls/22 boys) of the screened patients had histologically documented CD, yielding a prevalence of 10%. Nineteen (41.9%) patients had developed CD within the initial four years of diagnosis with T1DM. Therefore, among the six confirmed CD patients, the average age at the onset of T1DM was 3.7 years. For twenty-four (57.5%) of the patients, exhibited no apparent clinical indications of CD, and their condition was only identified through systematic screening. This study showed a high prevalence rate of CD associated with type 1 diabetes T1DM, particularly among young children. The results of this paper indicate one of the highest prevalence rates reported in the existing literature for the coexistence of CD and T1DM. These findings may suggest the necessity of a systematic screening of CD in T1DM patients.

Accuracy of the No-Biopsy Approach for the Diagnosis of Celiac Disease in Adults: A Systematic Review and Meta-Analysis

Background & AimsCurrent international guidelines recommend duodenal biopsies to confirm the diagnosis of coeliac disease in adult patients. However, growing evidence suggests that IgA anti-tissue transglutaminase (tTg) antibody levels ≥10 times the upper limit of normal (ULN) can accurately predict coeliac disease, eliminating the need for biopsy. We performed a systematic review and meta-analysis to evaluate the accuracy of the no-biopsy approach to confirm the diagnosis of coeliac disease in adults. MethodsWe systematically searched MEDLINE, EMBASE, Cochrane Library and Web of Science from January 1998 to October 2023 for studies reporting the sensitivity and specificity of IgA-tTG ≥10×ULN against duodenal biopsies (Marsh grade ≥2) in adults with suspected coeliac disease. We used a bivariate random-effects model to calculate the summary estimates of sensitivity, specificity, positive and negative likelihood ratios. The positive and negative likelihood ratios were used to calculate the positive predictive value (PPV) of the no-biopsy approach across different pre-test probabilities of coeliac disease. The methodological quality of the included studies was evaluated using the QUADAS-2 tool. This study was registered with PROSPERO, number CRD42023398812. ResultsA total of 18 studies comprising 12,103 participants from 15 countries were included. The pooled prevalence of biopsy-proven coeliac disease in the included studies was 62% (95% CI, 40% - 83%). The proportion of patients with IgA-tTG ≥10×ULN was 32% (95% CI, 24% - 40%). The summary sensitivity of IgA-tTG ≥10×ULN was 51% (95% CI, 42% - 60%), and the summary specificity was 100% (95% CI, 98% - 100%). The area under the summary receiver operating characteristic curve was 0.83 (95% CI, 0.77 – 0.89). The PPV of the no-biopsy approach to identify patients with coeliac disease was 65%, 88%, 95%, and 99% if coeliac disease prevalence was 1%, 4%, 10% and 40%, respectively. Between-study heterogeneity was moderate (I2 =30.3%), and additional sensitivity analyses did not significantly alter our findings. Only one study had a low risk of bias across all domains. ConclusionThe results of this meta-analysis suggest that selected adult patients with IgA-tTG ≥10×ULN and a moderate to high pre-test probability of coeliac disease could be diagnosed without undergoing invasive endoscopy and duodenal biopsy.

Effectiveness of a gluten-free diet on the autoantibody frequency of endocrine and neuron disorders in patients with celiac disease

Several possible associations between different types of autoimmune diseases have been reported, therefore this study aimed to investigate the relationship between celiac disease (CD) and some related autoimmune diseases by determining the effect of gluten on severity of these diseases. Two hundred blood samples were collected, 50 samples were withdrawn from healthy donors as a control group, 75 were collected from newly diagnosed (ND) CD patients, while the remaining blood samples (75) were obtained from the same patients after 4 months of gluten free diet (GFD) regime. Sera were separated to measure the level of anti-tissue transglutaminase IgA (tTG-IgA), anti-pituitary IgG, anti- thyroid peroxidase IgG (TPO- IgG), anti-islet IgG and anti-ganglioside IgG (IU/ml) by enzyme linked immunosorbent assay (ELISA). To analyze the results and compare between groups, GraphPad Prism was utilized. The results recorded high significant elevation (p&gt;0.0001) in the concentrations of all autoantibodies of both ND and GFD groups compared with their concentrations in the control group. Furthermore, after 4 months of GFD, all autoantibodies concentrations revealed highly significant decreases (p&gt;0.0001) as compared with ND. Regarding the correlation of all studied autoantibodies with anti tTG-IgA, only anti-ganglioside IgG levels were weakly correlated in pre-GFD treatment patients, meanwhile anti-ganglioside IgG and anti-pituitary IgG were also recorded weak correlations in post- GFD of CD patients. This study concluded that GFD helps to reduce the severity of endocrine and neuron autoimmune disorders in addition to CD, which have been proved by decreasing in the level of their diagnostic autoantibodies.

Prevalence of IgA Anti-tissue Transglutaminase Antibody in a Cohort of Iranians Patients with Inflammatory Bowel Disease

Abstract Background and Aims Some studies have reported the coexistence of inflammatory bowel disease (IBD) and celiac disease (CD). However, the prevalence of anti-tissue transglutaminase antibodies (IgA and IgG) and their screening value in patients with IBD is not yet clear. This study aimed to assess the prevalence of IgA anti-tTG and its potential correlation with disease status in patients with IBD. Materials and Methods This cross-sectional study was conducted on 110 patients with confirmed IBD diagnosis at Ghaem Hospital, Mashhad, Iran. For each patient, all demographic and clinical data including age, extra intestinal manifestations, underlying diseases, types of diseases, and surgical history were collected. IgA anti-tissue transglutaminase titers were assessed by enzyme-linked immunosorbent assay. Results None of the patients with IBD were positive for IgA anti-tTG antibodies, with a mean titer of 3.31 ± 1.3 AU/mL. Also, the mean titers were not associated with age, gender and various disease clinical features including the disease history, underlying disease, diagnosis type, extraintestinal manifestations, and surgery history. Conclusion No significant prevalence pattern of IgA anti-tTG antibody was observed in patients with IBD. Accordingly, serological screening for CeD is not recommended in IBD patients, unless in a relevant clinical CeD suspicion.

Sieving out non-celiac gluten sensitivity amongst patients with irritable bowel syndrome

ObjectivesIt is challenging to make diagnosis of non-celiac gluten sensitivity/non-celiac wheat sensitivity (NCGS/NCWS) in clinical practice, since there is no biomarker and diagnosis is based on response to gluten-free-diet (GFD). We used anti-gliadin antibody (AGA) for screening patients with IBS for gluten-sensitivity. Methods492 Adult-patients with IBS underwent screening for celiac disease and gluten-sensitivity using IgA anti-tissue transglutaminase antibody and IgA-AGA and IgG-AGA, respectively. Patients with positive AGA (IgA and/or IgG) were invited to follow GFD, those willing were put on GFD for 6-weeks. Responsive patients were given gluten re-challenge. Diagnosis of NCGS was confirmed if they had recurrence of symptoms. ResultsOf 492 patients with IBS, AGA was positive in 61(12.4 %), hence suspected to have gluten-sensitivity. Of 31 who agreed to participate and followed GFD for 6-weeks, 17 (54.8 %) had complete (>30 % improvement) and 10(32.2 %) had partial (>20 % improvement) response. All 17 complete-responders were given gluten re-challenge for 6-weeks, symptoms recurred in all and hence were confirmed to have NCGS/NCWS. Significant decrease in AGA levels occurred almost in all GFD-responders. Conclusions12.4 % IBS patients have biological evidence of gluten/wheat-sensitivity. Almost 87 % patients with IBS having AGA responded to GFD. The value of AGA may further be explored as a biomarker for screening for the presence of NCGS, before recommending this test for the clinical practice.

B-062 A Self-Imposed Gray Area? Analysis of Anti-Tissue Transglutaminase and Anti-Endomysial Antibody Discordance in a Celiac Disease Screening Serology Testing Algorithm

Abstract Background Celiac disease (CD) is an autoimmune enteropathy affecting around 1% of the population. While occasionally asymptomatic, the disease can present in a variety of ways and can be triggered by dietary gluten at any age. CD serology, including anti-tissue transglutaminase (anti-tTG) IgA and/or IgG, anti-endomysial antibody IgA and/or IgG, and anti-deamidated gliadin peptide IgA and/or IgG, is a key tool for CD screening, diagnosis, and monitoring. Of these tests, the clinical utility of anti-EMA testing has been questioned due to its high cost and limited sensitivity: 5–10% of CD patients do not test positive for anti-EMA and a negative anti-EMA does not rule out CD. The objective of this study is to: 1) evaluate the concordance between anti-tTG and anti-EMA serology test results, and 2) assess the clinical validity of our current CD reflex testing algorithm in which every positive anti-tTG test result goes on for anti-EMA testing. Methods Using our laboratory’s information system, we conducted a retroactive study on patients who underwent CD serology testing at our institution. Query was performed for all patient data [pediatric (&amp;lt;18 years) and adult (&amp;gt;18 years)] collected between April 2020 and August 2022 for anti-tTG IgA performed on the BioPlex 2200 (BioRad Laboratories Inc., Hercules, CA) and anti-EMA IgA (Euroimmun, Germany) (N = 124 308). Vendor-supplied clinical sensitivity and specificity are as follows: anti-tTG IgA 94.3% sensitivity, 98.8% specificity; anti-EMA IgA 95.3% sensitivity and 98.0% specificity. Results From our data, we calculated a mean positive agreement between our anti-tTG IgA and anti-EMA test results of 53.2% (95% confidence interval (CI) 47.5–58.8%) for all anti-tTG IgA positive cases (N = 6691, 5.4% of total anti-tTG IgA test results). The agreement between anti-tTG IgA and anti-EMA test results is improved if multiples of the upper limit of normal (ULN) for anti-tTG IgA is applied. The mean positive agreement between anti-tTG IgA and anti-EMA test results when the anti-tTG result is &amp;gt;10x ULN is 98.4% (95% CI 97.7–99.2%). However, if an anti-tTG IgA cutoff of &amp;lt;10x ULN is employed a mean positive agreement of 32.3% (95% CI 25.8–38.7%) is observed. At an anti-tTG IgA cutoff of &amp;lt;3x ULN, the mean positive agreement is just 11.8% (95% CI 8.2–15.4%). These findings are consistent in both pediatric (N = 29 381) and adult (N = 94 961) populations and are problematic as 45.4% of our positive anti-tTG IgA test results are accompanied by a negative anti-EMA. Conclusion The agreement between anti-tTG IgA and anti-EMA is dependent on the value of anti-tTG IgA with greater agreement observed with increasing anti-tTG IgA values. As all specimens at our institution with positive anti-tTG IgA test results are automatically reflexed for anti-EMA testing, has led to physician confusion as the majority of patients are falling into a gray area with conflicting CD serology test results. Our algorithm is also out of line with most CD screening guidelines that suggest an initial positive anti-tTG test result is followed up with biopsy. Finally, discontinuing anti-EMA reflex testing could result in cost savings of approximately $120 000 CAD per year.

Serum anti-tissue transglutaminase IgA and prediction of duodenal villous atrophy in adults with suspected coeliac disease without IgA deficiency (Bi.A.CeD): a multicentre, prospective cohort study

Whether coeliac disease in adults can be diagnosed with serology alone remains controversial. We aimed to evaluate the accuracy of serum anti-tissue transglutaminase IgA (tTG-IgA) in the diagnosis of coeliac disease. In this multicentre, prospective cohort study, adult participants (aged ≥18 years) with suspected coeliac disease without IgA deficiency who were not on a gluten-free diet and who had a local serum tTG-IgA measurement, were enrolled from Feb 27, 2018, to Dec 24, 2020, by 14 tertiary referral centres (ten from Europe, two from Asia, one from Oceania, and one from South America) to undergo local endoscopic duodenal biopsy. Local serum tTG-IgA was measured with 14 different test brands and concentration expressed as a multiple of each test's upper limit of normal (ULN), and defined as positive when greater than 1 times the ULN. The main study outcome was the reliability of serum tests for the diagnosis of coeliac disease, as defined by duodenal villous atrophy (Marsh type 3 or Corazza-Villanacci grade B). Histology was evaluated by the local pathologist, with discordant cases (positive tTG-IgA without duodenal villous atrophy or negative tTG-IgA with duodenal villous atrophy) re-evaluated by a central pathologist. The reliability of serum tests for the prediction of duodenal villous atrophy was evaluated according to sensitivity, specificity, positive predictive value, negative predictive value, and the area under the receiver operating characteristic curve (AUC) for categorical and continuous data. We enrolled 436 participants with complete local data on serum tTG-IgA and duodenal histology (296 [68%] women and 140 [32%] men; mean age 40 years [SD 15]). Positive serum tTG-IgA was detected in 363 (83%) participants and negative serum tTG-IgA in 73 (17%). Of the 363 participants with positive serum tTG-IgA, 341 had positive histology (true positives) and 22 had negative histology (false positives) after local review. Of the 73 participants with negative serum tTG-IgA, seven had positive histology (false negatives) and 66 had negative histology (true negatives) after local review. The positive predictive value was 93·9% (95% CI 89·2-98·6), the negative predictive value was 90·4% (85·5-95·3), sensitivity was 98·0% (95·3-100·0), and specificity was 75·0% (66·6-83·4). After central re-evaluation of duodenal histology in 29 discordant cases, there were 348 true positive cases, 15 false positive cases, 66 true negative cases, and seven false negative cases, resulting in a positive predictive value of 95·9% (92·0-99·8), a negative predictive value of 90·4% (85·5-95·3), a sensitivity of 98·0% (95·3-100·0), and a specificity of 81·5% (73·9-89·1). Either using the local or central definition of duodenal histology, the positive predictive value of local serum tTG-IgA increased when the serological threshold was defined at increasing multiples of the ULN (p<0·0001). The AUC for serum tTG-IgA for the prediction of duodenal villous atrophy was 0·87 (95% CI 0·81-0·92) when applying the categorical definition of serum tTG-IgA (positive [>1 × ULN] vs negative [≤1 × ULN]), and 0·93 (0·89-0·96) when applying the numerical definition of serum tTG-IgA (multiples of the ULN). Additional endoscopic findings included peptic gastritis (nine patients), autoimmune atrophic gastritis (three), reflux oesophagitis (31), gastric or duodenal ulcer (three), and Barrett's oesophagus (one). In the 1-year follow-up, a midgut ileum lymphoma was diagnosed in a woman on a gluten-free diet. Our data showed that biopsy could be reasonably avoided in the diagnosis of coeliac disease in adults with reliable suspicion of coeliac disease and high serum tTG-IgA. None.

Helicobacter Pylori and Celiac Disease Antibody Positivity Have a Higher Prevalence in Patients With Distal Gastrectomy: A Cross-Sectional Retrospective Study.

Aims and objectives Distal gastrectomy was a widely used therapeutic option for peptic ulcer and gastroesophageal reflux disease until quite recently. The consequences of anatomical and physiological changes following surgery in the gastric mucosa have been the object of interest for the scientist. In this study, we aimed to determine whether Helicobacter pylori (HP) infection and celiac disease were more common in patients with a history of distal gastrectomy. Materials and methods This is an observational retrospective study conducted at Giresun University Faculty of Medicine. The medical files of 35 patients with dyspepsia who had a history of distal gastrectomy for benign etiologies (antrectomy group) and 50 patients with dyspepsia (control group) were retrospectively analyzed. Results There were more males and older patients in the antrectomy group. Concerning the lab parameters, platelets, lymphocyte, and albumin levels were significantly lower, and urea, creatinine, anti-Endomisium Ig A (anti-EMA), and anti-tissue transglutaminase IgA (anti-tTGA) antibody positivity were significantly higher in the antrectomy group. Gastric biopsy results revealed a higher positivity of HP, atrophy, neutrophil, and lymphocytes in the antrectomy group. Correlation analysis revealed an inverse correlation between albumin and anti-EMA/atrophy positivity whereas a positive correlation between anti-EMA and HP/atrophy positivity. Conclusions HP infection and coeliac disease (CD) could be the problems that distal gastrectomy patients with dyspepsia can face during their follow-up. Concerning the pre-malignant potential of HP, its screening and eradication should be performed to prevent the malignant transformation of the remnant gastric tissue.

HMGB1 is related to disease activity in children with celiac disease

IntroductionWe aim to evaluate of the relationship between high mobility gene box-1 (HMGB1) levels and clinical, laboratory and histopathological findings at diagnosis and in remission in children with Celiac Disease (CD). Material and MethodsThe study included 36 celiac patients at diagnosis, 36 celiac patients in remission, and 36 healthy controls. Patients with intestinal pathologies other than CD, and accompanying inflammatory and/or autoimmune diseases were excluded. Relationship between HMGB1 levels and clinical, laboratory and histopathological findings were evaluated. ResultsA total of 72 celiac patients [36 (18 girls, 18 boys, mean age 9.41±3.9 years) in group 1 and 36 (18 girls, 18 boys, mean age 9.91±3.36 years) in group 2] and 36 healthy controls in group 3 (19 girls, 17 boys, mean age 9.56±4 years) were included. The HMGB1 level was significantly higher in group 1 compared to group 2 and group 3 [36.63 (17.98–54.72) ng/ml vs 20.31 (16.89–29.79) ng/ml, p = 0.028 and 36.63 (17.98–54.72) ng/ml vs 20.38 (17.54–24.53) ng/ml p = 0.012, respectively]. A serum HMGB-1 level of 26.553 ng/ml was found to be a cut-off value for the CD with 61% sensitivity, 83% specificity, 78% positive predictive value, and 68% negative predictive value. Higher HMGB1 values were seen in patients with intestinal findings, anemia, anti-tissue transglutaminase IgA levels that were greater than 10 times upper limit of normal, and patients with a higher degree of atrophy as classified by Marsh-Oberhuber. ConclusionsIn conclusion, it was thought that HMGB-1 might be a marker that reflects the severity of atrophy at the time of diagnosis and could be used to control dietary compliance in the follow-up. However, there is need for larger population studies in order to evaluate its value as a serological marker for the diagnosis and follow-up of CD and to find a more reliable cut-off value.

Mode of presentation and performance of serology assays for diagnosing celiac disease: A single-center study in the United Arab Emirates.

To characterize patients with celiac disease (CD), examines the clinical spectrum of CD, and evaluate the performance of serologic tests used for CD screening, in the United Arab Emirates (UAE). Medical charts of patients received at the Digestive Diseases Institute of Cleveland Clinic Abu Dhabi from January 2015 to December 2020 were reviewed. Patients who were screened for four serologic biomarkers (anti-tissue transglutaminase IgA [Anti-tTG-IgA], anti-tissue transglutaminase IgG [Anti-TtG-IgG], anti-deamidated gliadin peptide IgG [Anti-DGP-IgG], and anti-deamidated gliadin peptide IgA [Anti-DGP-IgA]) were included. Histopathology was performed on patients with the seropositive test. Marsh score > 1 considered to confirm CD. Characteristics of the Anti-tTG-IgA seropositive patients were described and that correlated with histopathologically confirmed CD were explored. Of the 6,239 patients, 1.4, 2.9, 4.7, and 4.9%, were seropositive to Anti-tTG-IgG, Anti-TtG-IgA, Anti-DGP-IgA, and Anti-DGP-IgG, respectively. Overall, 7.7% were seropositive to either of the four biomarkers. Of the biopsy-screened 300 patients, 38.7% (1.9% of the total serologically screened) were confirmed with CD. The mean age of Anti-TtG-IgA seropositive patients was 32.1 ± 10.3 SD years, 72% of them were females, and 93.4% were Emirati. In those patients, overweight (28.7%) and obesity (24.7%) were common while 5.8% of patients were underweight. Anemia prevalence was 46.7%, 21.3% had Gastroesophageal reflux disease (GERD), 7.7% with autoimmune thyroid disease, 5.5% (type 1), and 3.3% (type 2) were diabetic. Vitamin D deficiency was observed in 47.8% of the Anti-TtG IgA seropositive patients. Twelve (10.3%) histopathologically confirmed CD patients were seronegative to Anti-TtG-IgA but seropositive to anti-DGP-IgA and/or Anti-DGP-IgG. Body mass index, GERD, autoimmune thyroid disease, type 1 diabetes, asthma, hemoglobin, and vitamin D concentration, were all correlated with biopsy-confirmed CD (P < 0.05). Compared to the gold-standard biopsy test, Anti-TtG-IgA had the highest sensitivity (89.7%) and specificity (83.7%). Three and two of every 100 patients were serologically (anti-tTG-IgA positive) and histopathologically diagnosed with CD, respectively. Although Anti-TtG-IgA is the most sensitive, specific, and commonly used test, one of every ten histopathologically confirmed patients and Anti-tTG-IgA seronegative were seropositive to Anti-DGP. To avoid missing patients with CD, a comprehensive serological investigation covering DGP-IgG/IgA is warranted.

Role of age in dynamics of autoantibodies in pediatric Celiac disease

BackgroundCeliac disease (CD) is characterized by elevated serum titers of autoantibodies IgA anti-tissue transglutaminase 2 (TGA-IgA) and IgA anti-endomysial (EMA), with small bowel mucosa atrophy. We evaluated age differences between CD children exhibiting variable antibody titers at diagnosis.MethodsCD children diagnosed between January 2014 and June 2019, according to 2012 ESPGHAN guidelines were studied. All had EMA and TGA-IgA measurements, while a proportion of them underwent esophagogastroduodenoscopy (EGD). Patients were grouped based on serum TGA-IgA titers normalized to the upper limit of normal (ULN) and differences in median age (years) assessed by analysis of variance (ANOVA) and creation of orthogonal contrasts.ResultsCD was diagnosed in 295 subjects (median age: 4.4 [IQR: 2.60–8.52]) with a biopsy sparing protocol (high titer: ≥ 10xULN) and in 204 by EGD biopsy. Of the latter, 142 (median age: 8.5 [IQR: 5.81–11.06]) and 62 (median age: 9.5 [IQR: 6.26–12.76]) had a low (< 5xULN) and a moderate (≥ 5 < 10xULN) TGA-IgA titer, respectively. Potential CD was diagnosed in 20 patients (median age: 3.6 [IQR: 2.47–6.91]). The median age was significantly lower in the no-biopsy group (ANOVA: F(3, 516) = 25.98, p < .001) than in low- and moderate titer groups (p < 0.0001), while there was no statistical difference between biopsy-sparing and potential CD groups.ConclusionCD patients with greatly elevated antibody titers (≥ 10xULN) were diagnosed at an earlier age than those with lower titers. This may indicate that an increase in TGA-IgA is independent of age and suggests a polarization of autoimmunity in younger individuals with higher serum antibody levels.

Early Antibody Dynamics in a Prospective Cohort of Children At Risk of Celiac Disease.

The purpose of this study was to identify possible serum biomarkers predicting celiac disease (CD) onset in children at risk. A subgroup from an ongoing, international prospective study of children at risk of CD was classified according to an early trajectory of deamidated gliadin peptides (DGPs) immunoglobulin (Ig) G and clinical outcomes (CD, potential CD, and CD autoimmunity). Thirty-eight of 325 children developed anti-tissue transglutaminase IgA antibody (anti-tTG IgA) seroconversion. Twenty-eight of 38 children (73.6%) showed an increase in anti-DGPs IgG before their first anti-tTG IgA seroconversion. Anti-DGPs IgG can represent an early preclinical biomarker predicting CD onset in children at risk.

Diagnostic performances of celiac disease serological tests among Saudi patients.

: The prevalence of celiac disease (CD) is relatively high in Saudi Arabia, and little is known about the accuracy of serological markers in the local population. This study aimed to assess the diagnostic performance of various serological markers for detecting CD in Saudi children and adults. We conducted a retrospective study of 148 CD patients and 512 controls to assess the diagnostic performances of IgA anti-tissue transglutaminase antibodies (TTG), IgG anti-TTG, IgA anti-deamidated gliadin peptide antibodies (anti-DGP), IgG anti-DGP, and endomysium antibodies (EMA). : Immunoglobulin A (IgA) anti-TTG was the most sensitive test [98.9% (95% confidence interval (CI) 94.1-99.8%)], while EMA was the most specific [100%, 95%CI 98.6-100%]. By applying the criteria of IgA anti-TTG titers ≥10 × upper limit of normal (ULN) and positive EMA, 57.3% of patients could have avoided intestinal biopsy. IgG anti-DGP test had a sensitivity of 85.9% (95% CI = 77.3-91.5%) and a specificity of 93.5% (95% CI = (90.0-95.9%). Titers of IgA anti-TTG, IgA anti-DGP, and IgG anti-DGP were higher in CD patients with the Marsh 3c class than in those with the Marsh 3b and Marsh 3a classes. IgG anti-TTG and IgA anti-DGP had no additional diagnostic value. : IgA anti-TTG and EMA are excellent CD markers in children and adults. The use of IgA anti-TTG titers ≥10 × ULN and positive EMA as criteria for CD diagnosis in children and adults might be a good alternative to intestinal biopsy.

Identification of celiac disease associated IgA nephropathy by IgA anti-tissue transglutaminase2 antibody deposits in archived formalin-fixed tissues.

The causal association between IgA nephropathy (IgAN) and celiac disease (CeD) is based on their clinical coexistence. In this prospective study, we screened patients with IgAN for CeD and explored the utility of analysis of IgA anti-TG2 antibody deposits, for establishing a causal association. Biopsy-proven patients of IgAN were screened for serum IgA anti-tissue transglutaminase antibody (IgA anti-tTG Ab) titer and thereafter were invited to undergo endoscopic duodenal biopsy. Corresponding duodenal and kidney biopsies were subjected to IgA anti-TG2 antibody colocalization study using dual-color immunohistochemistry and immunofluorescence techniques. Additionally, kidney biopsies from 105 patients with IgAN who did not give consent for serology analysis, 30 non-IgA nephropathies, and 10 normal controls were also included. Dual-color-stained slides were interpreted based on stain distribution and intensity scores, and Pearson's index >0.3-1 on confocal imaging was considered significant. Of a cohort of 151 patients with IgAN, 32 consented to undergo sero-screening and 5 of them had high serum anti-tTG Ab titer. Two out of the latter consented to endoscopic duodenal biopsies, in whom modified Marsh grade 3b changes were identified. Strong IgA anti-TG2 antibody deposits were noted in the kidney and duodenal biopsies of these patients. One patient out of non-consenting 105 patients with IgAN and 3 out of 30 patients with other non-IgA nephropathies also showed IgA anti-TG2 deposits. None of the healthy kidney tissues showed IgA anti-TG2 Ab deposits. Co-localized IgA anti-TG2 deposits in the kidney biopsies in patients with IgAN help to establish a pathogenic link with CeD. A small proportion of patients with IgAN have associated CeD.

HEART RATE VARIABILITY IS AFFECTED IN YOUNG ADULT CELIAC PATIENTS, INDICATING AUTONOMIC DYSFUNCTION AND INCREASED CARDIOVASCULAR RISK

Aim: Celiac Disease (CD) is a common autoimmune disease that can present at any age with varied symptoms. Cardiac involvement including vascular and arrhythmic disturbances has an important prognostic value in patients with autoimmune disorders. The aim of this study was to evaluate the effects of CD on cardiovascular autonomic functions by measuring the indices of heart rate variability (HRV).&#x0D; Materials and Methods: Ninety-one CD patients and the ninety-three healthy volunteers were included in the study. We examined both time domain and frequency domain indices of HRV measured by 24-hour ambulatory electrocardiography.&#x0D; Results: All of the time domain and frequency domain HRV parameters, with the exceptions of low frequency power and low frequency to high frequency ratio, were significantly lower in patients with CD compared to the control (p &lt; 0.01). This difference retained for most of the HRV parameters when daytime and nighttime HRV parameters were compared separately. Correlation analysis revealed significant associations of HRV parameters with hemoglobin and ferritin levels and with duration of CD (p &lt; 0.01). No correlation was found between HRV parameters and anti-tissue transglutaminase IgA and IgG levels which indicate the activity of the disease.&#x0D; Conclusion: The study confirmed that patients with CD have reduced HRV, indicating the presence of objective autonomic dysfunction and increased cardiovascular risk.

Evaluation of the effect of probiotics on celiac patients

ABSTRACT&#x0D; Aims:It was aimed to evaluate the effect of yogurt consumption containing Streptococcus thermophilus, Lactobacillus delbrueckii subsp. bulgaricus and Lactobacillus acidophilus probiotic bacteria on the celiac markers, biochemical values and clinical symptoms of celiac diseas.&#x0D; Methods:Fifty celiac patients with positive anti-tissue transglutaminase(anti-tTG) IgA values were evaluated prospectively. The patients were divided into two groups. One group was recommended only gluten-free diet(GFD),while the other group was recommended to eat 200 mL probiotic yogurt containing Streptococcus thermophilus, Lactobacillus delbrueckii subsp. bulgaricus and Lactobacillus acidophilus daily in addition to GFD. The change in biochemical values, vitamin levels, celiac markers and clinical symptoms of both groups was examined after three months of yogurt consumption.&#x0D; Results:Anti-tTg IgA,anti-deamidated gliadin peptide antibody(anti-DGP) IgA and anti-endomysium antibody(EMA) levels of the two groups decreased significantly after three months in both groups.There was a significant decrease in EMA levels in the probiotic yogurt+GFD group(p=0.025) when compared with GFD group. Vitamin D and ferritin levels of the probiotic yogurt+GFD group increased significantly after three months(respectively p=0.004;p=0.039). Folate, vitamin D and iron levels of GFD group increased significantly(respectively p=0.002;p=0.007;p=0.007). In both groups, clinical symptoms significantly decreased after three months. There was a significant decrease in the abdominal pain symptoms in the probiotic yogurt+GFD group when compared with GFD group(p=0.012).&#x0D; Conclusion:Gluten-free diet and consumption of yogurt containing Streptococcus thermophilus, L. delbrueckii ssp. bulgaricus and Lactobacillus acidophilus were found to be statistically significant in decreasing EMA levels and abdominal pain from irritable bowel syndrome (IBS) type symptoms of celiac patients when compared with GFD only.

Characteristics of Pediatric Celiac Disease in Southern West Virginia

Purpose Celiac disease (CD) is a disorder in which gluten ingestion triggers an autoimmune response causing inflammation and damage to the small intestine. With improved awareness and screening availability, prevalence and variation in clinical presentation have subsequently increased. Thus, our study identified the disease characteristics and presentation patterns of pediatric CD in southern West Virginia. Methods We retrospectively reviewed charts for pediatric patients (age &lt;18 years) diagnosed with CD during a 10-year period at a tertiary care hospital. Results A total of 59 patients met inclusion criteria. The mean age of diagnosis was 10.0+4.6 years, with 61% of patients being female. One-third of cases were asymptomatic and diagnosed from screenings of patients with hypothyroidism or type 1 diabetes mellitus. In symptomatic patients (n=40), abdominal pain was the most common presenting symptoms (78%), followed by constipation (30%). Classical symptoms of diarrhea and failure to thrive/unexplained weight loss were less common (n=9). At diagnosis, anti-tissue transglutaminase (tTG) IgA antibodies and deamidated gliadin peptide IgG antibodies were both positive in 88% of cases, and endomysial antibodies were positive in 70% cases. One-year post-diagnosis clinic follow-up rate was 63%. A gluten-free diet improved symptoms and tTG IgA serology levels in all patients with follow-up. Conclusion Our data fills in the gap of the paucity of information available about CD in children from Appalachia. A high index of suspicion is required to screen and diagnose CD as many patients are either asymptomatic or lack classical findings. A gluten-free diet is a highly effective treatment, although follow-up after initial diagnosis remains a challenge.