anti-tTG IgA Research Articles

B-092 Effect of the Increased Specificity in a Recombinant anti-tTG Assay on a Celiac Disease Diagnostic Algorithm

Abstract Background Celiac disease is an autoimmune disease where ingestion of gluten results in damage in the small intestine. Celiac disease is estimated to affect 1 in 100 people worldwide, but only 30% of individuals are correctly diagnosed. If celiac disease is neither diagnosed nor treated, this can lead to additional health problems such as type 1 diabetes, multiple sclerosis, short stature, coronary artery disease and small intestine cancers. The celiac disease diagnostic algorithm at our institution begins with determination of IgA levels in the patient. If the patient is not IgA deficient (IgA > 7 mg/dL), an anti-tissue transglutaminase (anti-tTG) IgA level is determined. In patients who have anti-tTG IgA ≥ 4U/mL, an endomysial antibodies (EMA) IgA is performed by indirect immunofluorescence (IFA). Inova Diagnostics updated the reagent from human-derived native antigen to a more specific assay containing a recombinant antigen. We investigated the impact of this change on the downstream testing in our algorithm. Methods The new assay was implemented in August of 2023, and the monthly test counts and percentage of abnormal results were counted for both anti-tTG IgA and EMA IFA before and after the new assay was implemented. Results As shown in Figure 1., switching to the new recombinant anti-tTG reagent resulted in a decrease in the number of anti-tTG IgA results that were classified as abnormal. Subsequently, the abnormal samples that advanced in the algorithm for EMA IFA testing had a higher percentage of abnormal results, while the number of tests performed was lower. Conclusions Use of a more specific anti-tTG assay results in reduction of false positive results, and tests that continue through the celiac disease algorithm are more likely to represent a true diagnosis of celiac disease.

Investigating the Role of Gluten Sensitivity in the Etiology of Autism Spectrum Disorder.

&lt;b&gt;Background and Objective:&lt;/b&gt; Autism Spectrum Disorder (ASD) is a range of neurodevelopmental disabilities that lack a clear etiology. To date, studies investigating the role of immune reactivity to gluten in ASD have been inconsistent. This study aimed to compare levels of gluten reactivity markers in 319 ASD patients to 172 of their unaffected siblings and 322 of unrelated healthy controls (UHC). &lt;b&gt;Materials and Methods:&lt;/b&gt; Patients younger than 12 years old diagnosed with ASD via experienced child psychiatrists and neuro-pediatricians were recruited and gluten reactivity markers and gastrointestinal (GI) complaints commonly found in children with ASD were also investigated. Serum levels of anti-gluten and anti-tissue transglutaminase IgA (anti-TTG IgA) were measured via ELISA. &lt;b&gt;Results:&lt;/b&gt; No significant differences were detected in IgA levels and IgG levels for anti-TTG among all groups (p<0.05). The anti-gliadin IgG levels were significantly higher in ASD patients and their siblings compared to the UHC group (p<0.05). Also, those IgG levels were not associated with any GI complaints or Electroencephalogram (EEG) abnormalities (p>0.05). &lt;b&gt;Conclusion:&lt;/b&gt; The data suggested gluten sensitivity has no role in ASD pathophysiology or its comorbid symptoms.

Association between Autoimmune Hepatitis and Celiac Disease among Egyptian Children and Adolescents

Abstract Background Celiac disease (CD) is an immune-mediated intolerance to gluten .CD has been recognized as a multisystem disorder which may affect other extra intestinal organs, such as the skin, thyroid, heart, nervous system, pancreas and liver. Individuals with CD are at increased risk of liver disease namely cryptogenic liver disorder and autoimmune liver disorder. However, until now, it remains unknown whether these two forms of liver disease are really different entities or only different severities of the same disorder. Objective To evaluate the association of CD with autoimmune hepatitis in pediatrics. Subjects and Methods This was a cross-sectional study that was conducted at the Pediatric Hepatology Clinic and Pediatric Gastroenterology Clinic, Children’s Hospital, Ain Shams University. The study included 2 groups of patients each comprised 20 children and adolescents as follow: Group I: Patients with established diagnosis of autoimmune hepatitis (AIH). All patients were receiving corticosteroids and azathioprine Group II: Patients with established diagnosis of CD. In group I patients with AIH, CD was screened for using anti-tissue transglutaminase (tTG) IgA in addition to measuring serum IgA to determine the need to measure anti-tTG IgG. Immunological markers (ANA, anti-smooth muscle antibody (ASMA) and liver and kidney microsomal (LKM) antibodies in addition to protein electrophoresis were done for group II patients with CD to screen for AIH. Results All patients in group I with AIH had normal serum IgA levels and were found negative for anti-tTG IgA. Also, group II patients with CD were negative for ANA, ASMA and LKM antibodies with normal protein electrophoresis. Conclusion The current study showed that CD does not seem to have significant association with AIH, however, the small sample size is a study limitation. Further wider scale studies are needed to evaluate the risk of AIH in CD.

Celiac disease prevalence in patients with idiopathic inflammatory myopathies, a cross-sectional study.

Up to 30% of patients with celiac disease (CD) suffer from concurrent autoimmune disease, compared to 3% of the general population. The association between CD and the current clinical phenotypes of inflammatory myopathies (IIM) patients has not been thoroughly addressed. Assess the CD features among patients with IIM and their relationship with the clinical phenotype and the myositis specific (MSA) and associated antibodies (MAA). For this cross-sectional study, we recruited 99 adult patients classified as IIM from a tertiary center in Mexico. We assessed serum MSA, MAA, and CD-associated autoantibodies (IgA anti-tissue transglutaminase (tTG) and both IgA and IgG anti-deaminated gliadin peptide (DGP)). Patients with highly suggestive serology for CD were then tested for IgG anti-endomysium antibodies, and a duodenal biopsy was performed. 70.7% of patients were positive for at least one antibody. Nine duodenal biopsies were taken, revealing findings compatible with celiac disease in two cases. Subjects with anti-MDA5 antibodies were more likely to have positive anti-tTG IgA antibodies (OR 6.76, 95% CI 1.85-24.62, P = 0.013) and suggestive CD serology (OR 6.41, 95% CI 1.62-25.29, P = 0.009). Patients with anti-Mi2 antibodies were more likely to have positive anti-DGP IgG antibodies (OR 3.35, 95% CI 1.12-9.96, P = 0.039), while positivity for these autoantibodies was less frequent in patients with anti-NXP2 antibodies (OR 0.22, 95% CI 0.06-0.80, P = 0.035). There is a higher prevalence of serologic and definite CD in patients with IIM compared to the general population. Identifying this subgroup of patients may have prognostic and therapeutic implications. Key points • The study estimated a serological celiac disease (CD) prevalence of 70.7% in patients with idiopathic inflammatory myopathies (IIM) and a biopsy-confirmed prevalence of 2%, suggesting that IIM patients should be considered a high-risk population for CD. • We identified a significant association between serological CD and the presence of anti-MDA5 and anti-Mi2 antibodies, suggesting a potential justification for celiac disease screening in this specific subgroup of patients. • The impact of gluten-free diets on IIM patients with serological markers of CD remains untested and warrants further investigation through prospective, randomized studies.

The use of anti-transglutaminase and anti-gliadin antibodies to compare the effect of gluten active and gluten-free diet patients suffering from celiac disease in child and adult

Celiac disease is an autoimmune disorder triggered by the ingestion of gluten in genetically susceptible individuals. The current study aimed to compare the levels of these antibodies in celiac disease patients on active gluten-containing diets and those on gluten-free diets to demonstrate the ability to get rid of Celiac Disease by Gluten-Free Diet. The study involved 100 participants, divided into 60 CD patients and 40 controls, where all participant match in age and gender. The patient group was further divided into two subgroups 40 active celiac and 20 GFD. Blood samples were obtained from all participants, and levels of anti-tTG and anti-gliadin antibodies were using Enzyme-Linked Immunosorbent Assay (ELISA) technology. The results showed The F test indicated a significant difference in the levels of anti-tTG and anti-gliadin antibodies between the active group (G1) and the diet group (G2) in comparison to the control group (G3), with a p-value less than 0.001. Upon conducting a deeper analysis using the least significant difference (LSD) on on anti-tTG IgA and IgG indicate that there are no significant differences between the patient groups G1 and G2, as evidenced by p-values of 0.120 for IgA. However, a significant difference was observed between G1 and G2 for IgG, with a p-value of 0.018. When comparing G1 with G3, and G2 with G3, significant differences were observed, with p-values less than 0.001. In the case of anti-gliadin IgA and IgG, the LSD test revealed a highly significant difference between G1 and G2, as indicated by a p-value less than 0.001. However, no significant differences were found between G1 and G3, with p-values of 0.499 for IgA and 0.110 for IgG. A highly significant difference was none the less observed between G2 and G3, with a p-value less than 0.001.In conclusion, This study highlights the importance of dietary adherence in celiac disease management. Patients on gluten-free diets had significantly lower levels of anti-TG and anti-gliadin antibodies, indicating better control of the autoimmune response. Monitoring these antibody levels can be a valuable tool in assessing the effectiveness of dietary interventions in celiac disease patients.

Frequency of microscopic colitis in patients presenting with chronic diarrhea.

Objective: To evaluate frequency of microscopic colitis in patients presenting with chronic diarrhea at a tertiary care hospital in Karachi, Pakistan. Study Design: Descriptive Cross-sectional study. Setting: Department of Gastroenterology, Liaquat National Hospital, Karachi, Pakistan. Period: January, 2022 to June, 2022. Material &amp; Methods: Patients presenting in out-patient department of age &gt;18 years of any gender with history of diarrhea &gt;1 month, normal thyroid tests, negative serology for Celiac disease (Anti TTG IgA and IgG), and normal colonoscopy findings including terminal ileum were enrolled in the study after written informed consent. MC diagnosis was established using clinical diarrhea history and colonic biopsy findings. Results: Total 130 patients were analyzed with median age of 38 (IQR= 28-55) years. Nearly half were females (n=67, 51.5%). All patients had normal colonoscopy findings. Out of 130 patients, microscopic colitis was seen among 7(5.4%) cases out of which 5(3.8%) had lymphocytic colitis and 2(1.5%) had collagenous colitis. Patients with and without MC shared the same characteristics. Conclusion: A lower microscopic colitis frequency was found in the studied sample. Lymphocytic microscopic colitis is predominant than collagenous microscopic colitis.

Diagnostic accuracy of a novel point-of-care test for simultaneous detection of anti-transglutaminase IgA and anti-deamidated gliadin IgG antibodies.

Point-of-care tests (POCTs) may have a role in detecting undiagnosed cases of Celiac disease (CD). We assessed the diagnostic accuracy of a novel POCT, compared with the conventional serological methods, for simultaneous anti-transglutaminase (tTG) IgA and anti-deamidated gliadin (DGP) IgG antibody detection. Furthermore, we evaluated the effect of different biological matrices (whole blood and serum) on test performance. Serum and whole blood from celiac or suspected celiac patients who underwent duodenal biopsy were assayed for the presence of anti-tTG IgA and anti-DGP IgG both with the reference standard methods (Thermo Fisher Scientific, Uppsala, Sweden) and with the POCT (PRIMA Lab SA, Balerna, Switzerland). 266 sera (101 negative and 165 positive) and 60 whole blood samples (34 positive and 26 negative) were included in the study. POCT for anti-DGP IgG showed a sensitivity of 84.3% and a specificity of 90.1%, with positive (PPV) and negative predictive values (NPV) of 91.07% and 82.73%. POCT for anti-tTG IgA showed a sensitivity of 98.31% and a specificity of 98.02%, with a PPV and NPV of 98.31% and 98.02%. Test accuracies were 86.94% and 98.17%, respectively. The agreement of the results between the two different matrices showed a strong correlation rate: 95% for anti-DGP IgG and 100% for anti-tTG IgA. The anti-tTG IgA/anti-DGP IgG-based POCT showed good diagnostic accuracy with comparable sensitivities and specificities to reference standard methods in detecting CD in symptomatic patients and could be considered as a mass screening test before referring to conventional serology.

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.

Evaluation of Frequency of Celiac Disease in Children with Idiopathic Epilepsy.

Extra gastrointestinal symptoms in celiac disease (CD), such as neurological manifestations, might be common in pediatrics. The present study aimed to evaluate the frequency of CD in children with idiopathic epilepsy. In a cross-sectional study, signs and symptoms of CD were evaluated in 40 children aged 2-14 years with idiopathic epilepsy who were referred to the Pediatric Neurology Clinic of Shahid Sadoughi Medical Sciences University, Yazd, Iran. Then, serum levels of tissue transglutaminase antibody (tTG) and total IgA were measured in them. Upper gastrointestinal endoscopy and small intestine biopsy were recommended for patients with abnormal serum IgA Anti-tTG. Eighteen girls and 22 boys with a mean age of 5.29±2.4 years were evaluated. In this study, only three patients (7.5%) with epilepsy had abnormal serum IgA Anti-tTG and serum Total IgA. Upper gastrointestinal endoscopy and pathological examination of duodenal biopsy of those three children reported total villous atrophy (Marsh type 3). The age of onset of seizures in children with CD was more than three years, while in children without CD, 62.2% of cases were less than three years. These results indicate that CD is associated with the age of onset of seizures in children. Due to the accompaniment of celiac with neurological manifestations, patients with neurological symptoms and gastrointestinal symptoms should be examined for celiac.

Diagnostic Accuracy of Tissue Transglutaminase and Combined Assay of Tissue Transglutaminase and Deamidated Gliadin Peptide in Children with Coeliac Disease: A Cross-sectional Study

Introduction: Coeliac Disease (CD) is a systemic immune disorder caused by gluten in genetically susceptible individuals. A serological screening assay for CD has been designed to detect Immunoglobulin A (IgA) and IgG anti-tissue Transglutaminase (a-tTG) and IgA and IgG Deamidated Gliadin Peptide antibodies (a-DGP) simultaneously. The seronegative gap can be closed when these two antigens are combined on a single solid phase. This is primarily because untreated CD children who are negative for antibodies of one of the antigens may exhibit a positive result for the other. Aim: To determine the diagnostic parameters {sensitivity, specificity, Positive Predictive Value (PPV), Negative Predictive Value (NPV)} of tTG-IgA and htTG-DGP (Coeliac fusion- a combination of IgA and IgG to human tTG and synthetic DGP) for the diagnosis of CD in clinically symptomatic children. Materials and Methods: This cross-sectional study was conducted at the Paediatric Outpatient Department (OPD) of Santokhba Durlabhji Memorial Hospital, Jaipur, Rajasthan, India from April 2023 to November 2023. The study population comprised 45 children (age &gt;6 months and &lt;18 years) showing clinical features of CD. Considering biopsy as the gold standard, the diagnostic parameters (sensitivity, specificity, PPV, NPV) of tTG-IgA and htTG-DGP were calculated with a 95% confidence interval for both tests. To determine the agreement between the two tests, Cohen’s kappa was calculated. A p-value less than 0.05 was considered statistically significant. Results: Out of the study population, 23 (46%) CD patients were in the age group of 3-6 years, while 13 (26%) patients were in the age group of 6-9 years. A total of 24 (53.3%) CD patients were males, and 21 (46.7%) were females. Chronic diarrhoea was the most common clinical feature in 31 (62%) patients. Considering duodenal biopsy as the gold standard, the study results showed that the anti tTG-IgA antibody test had a sensitivity of 91.1%, specificity of 80%, PPV of 97.6, and NPV of 50%. In comparison, the htTG-DGP antibody test had a sensitivity of 95.6%, specificity of 100%, PPV of 100%, and NPV of 71.43%. Conclusion: Currently, tTG-IgA is considered the best CD screening test. However, the inclusion of DGP IgG could increase diagnostic sensitivity, and a Combined IgA/G-DGP/ tTG assay could be even better than tTG-IgA for the diagnosis of childhood CD.

Myocardial function using two dimension speckle-tracking echocardiography in children with celiac disease

The prevalence of cardiac complications linked to celiac disease (CD) is on expanding. This study aimed to evaluate the cardiac function in children with CD using two dimensional speckle tracking echocardiography (2D-STE) to detect early myocardial dysfunction, if any. This cross-sectional study included 40 children with CD as the patient group and 40 healthy age- and sex-matched children served as the control group. High sensitive troponin T (Hs-troponin T), anti-tissue transglutaminase immunoglobulin A (tTG-IgA), hemoglobin, ferritin, albumin, and vitamin D levels were measured in all participants. Conventional, tissue Doppler imaging (TDI), and 2D-STE were performed for all included children. Conventional echocardiographic parameters showed no significant difference between the two groups. Left ventricular global longitudinal strain (LV GLS) obtained by 2D-STE was substantially lower in children with CD than the control group; however, myocardial performance index (MPI) obtained by TDI was significantly higher in children with CD. Hs-troponin T levels were comparable in both groups. LV GLS was positively correlated with hemoglobin, ferritin, and albumin level, but it was inversely correlated with the duration of the disease and anti tTG-IgA. Conclusion: 2D-STE can detect subclinical early cardiac dysfunction in children with CD and this cardiac injury correlated to the duration and severity of the disease and some nutritional deficiency in these children.What is Known:• The prevalence of cardiac complications linked to celiac disease (CD) is on expanding.• Only one study evaluated cardiac function in children with CD using two dimensional speckle tracking echocardiography (2D-STE).What is New:• Our study found that 2D-STE can detect early subclinical cardiac dysfunction in children with CD. Cardiac injury in theses children correlated to the duration and severity of the disease, hemglobin, ferritin, and albumin levels.

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.

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.

B-055 Comparison of Sensitivity Between Tissue Anti-Transglutaminase and Anti-Endomysium IgA and IgG in Serological Screening for Celiac Disease in a Large Clinical Laboratory in Brazil

Abstract Background Celiac Disease (CD) is a genetic and autoimmune disorder characterized by permanent intolerance to gluten found in foods, resulting in small intestine injury in children and adults. Anti-tissue transglutaminase (anti-tTG) and anti-endomysium (anti-EM) antibodies are important serological markers of this disease. The aim was to analyze the analytical sensitivity of these markers in a large-scale Clinical Laboratory routine. Methods We employed a pure sample and a series of dilutions in the analysis of the functional sensitivity of each marker (anti-tTG IgA/IgG and anti-EM IgA/IgG) and a database survey of a large Clinical Laboratory in Sao Paulo/Brazil, from January to December 2021, analyzing 60 000 samples with concomitant results of anti-tTG IGA and anti-EM IgA and 7075 samples with results of anti-tTG IgG and anti-EM IgG, from patients with no defined clinic condition. The anti-tTG tests were performed by fluorescence enzyme immunoassay (FEIA) and the anti-EM tests by indirect immunofluorescence (IFI), with an initial dilution of 1:10, following the manufacturer's recommendations. Results The determination of functional sensitivity by checking the maximum dilution of antibody detection showed higher sensitivity of the anti-tTG IgA and IgG test (dilution factor 0.3 for both) compared to the anti-EM IgA and IgG (dilution factor 0.7 for both). Of the 60 000 samples analyzed for IgA markers, 59 083 (98.5%) were negative for both tests. Of the remaining 917 samples (1.5%), 609 (66.4%) were positive for both anti-tTG IgA and anti-EM IgA, 308 (33.6%) were positive only for anti-tTG IgA, and we did not observe any sample anti-tTG IgA negative with anti-EM IgA positive. Of the 7075 samples analyzed for IgG markers, 7032 (99.4%) were negative for both tests. Of the remaining 43 samples (0.6%), 18 (41.9%) were positive for anti-tTG IgG and anti-EM IgG, 14 (32.6%) were positive only for anti-tTG IgG, and 1 (2.3%) were positive only for anti-EM IgG. Conclusion The study showed greater sensitivity of anti-tTG compared to anti-EM for both IgA and IgG, in agreement with the literature data. The anti-tTG IgA test, in individuals without immunoglobulin A (IgA) deficiency, is recommended as the initial test in suspicion of celiac disease by current scientific guidelines on celiac disease. Based on our findings and literature data, in individuals with IgA deficiency, we suggest a screening using two automated IgG markers, tTG IgG and deamidated gliadin IgG (DG IgG). In addition to the lower sensitivity of anti-EM, indirect immunofluorescence (IFI), compared to the fully automated FEIA method, is a more subjective, observer-dependent, and labor-intensive methodology to be used as screening in large-scale Clinical Laboratory routines.

Celiac Disease in Uzbek Children: Insights into Disease Prevalence and Clinical Characteristics in Symptomatic Pediatric Patients.

A few studies on pediatric Celiac Disease (CD) are available from Central Asia. Recent immunogenetic research has highlighted that the HLA-DQ2/8 genetic predisposition to CD as well as the dietary intake of gluten in this geographical area, are comparable to other regions of the world where CD prevalence is known to be 1% or higher. This is a prospective and cross-sectional study investigating the prevalence and clinical characteristics of CD in symptomatic children referred to the pediatric gastroenterology department of a tertiary hospital in Uzbekistan from 1 September 2021, until 31 July 2022. In addition to collecting the relevant information related to clinical manifestations and laboratory analyses from the clinical files, a specific survey was also administered to patients' guardians. Serological, histopathological, and immunogenetic parameters specific to CD, fecal zonulin, and pancreatic elastases were assessed in CD patients. The study population consisted of 206 children. Overall, almost all of them (n = 192; 93.2%) were referred because of gastrointestinal manifestations, which were associated with extra-gastrointestinal manifestations in most cases (n = 153; 74.3%); a minority (n = 14; 6.8%) was mainly referred due short stature and/or growth failure only. Among all of these study participants, CD was diagnosed in 11 children (5.3%). Notably, although diarrhea was similarly reported in CD and non-CD patients, watery diarrhea (type 7 according to the Bristol stool scale) was much more frequently and significantly observed in the former group. All of these CD patients showed anti-tTG IgA 10 times higher than the upper normal limit, except one child with lower serum levels of total IgA; however, all of them received a diagnostic confirmation by histopathological analysis due to the lack of EMA testing in the country. Notably, most CD children (82%) showed a Marsh III histological grading. Around half patients (54.5%) showed zonulin values above the reference range, whereas none showed insufficient levels of pancreatic elastase. However, no correlation or association between zonulin and clinical, laboratory, histopathological, and immunogenetic parameters was found. This study may further suggest a relevant prevalence of CD in Uzbek children, based on this partial picture emerging from symptomatic patients only. Additionally, we highlighted the prevalence of typical CD forms with watery diarrhea, which should strongly support a full diagnostic work-up for CD in the local clinical setting. The high levels of anti-tTG IgA and high Marsh grade might also lead us to speculate a significant diagnostic delay despite the classical clinical expression of CD.

#3121 THE EFFECTIVENESS OF A GLUTEN-FREE DIET IN PATIENTS WITH IGA NEPHROPATHY

Abstract Background and Aims Modern data from the world literature confirm the association of IgA nephropathy (IgAN) and celiac disease. The inclusion of a gluten-free diet (GFD) in the diet has a beneficial effect not only on gastrointestinal symptoms, but also reduces the clinical and laboratory activity of IgAN. The aim of this study was to evaluate the effect of a gluten-free diet on the course of IgAN using general clinical and immunological tests 6 months after the start of its use. Method 65 patients with morphologically confirmed IgAN were included in the study. To detect a violation of gluten metabolism, screening determination of the level of IgA antibodies to tissue transglutaminase (Anti-TTG IgA) and IgA antibodies to deamidated gliadin peptides (Anti-DPG IgA) was performed. According to the results of the screening examination, a group of patients with the level of antibodies exceeding the reference values were formed (group 1, n = 13) and a group of patients in whose blood did not exceed the reference values, or were absent at all (group 2, n = 52). Patients of both groups were recommended GFD for a period of at least 6 months. The effectiveness of GFD was evaluated by the following indicators: protein in urine (g/l); red blood cells in urine (RBCs) (hpf); daily proteinuria (g/day); blood creatinine (mmol/l), GFR calculated by the formula CKD-EPI (ml/min /1.73 m2) at the beginning of the study and 6 months after the inclusion of dietary recommendations. Statistical analysis of the data obtained was carried out using the statistical program SPSS Statistics 26.0 (IBM, USA). When comparing quantitative indicators, the distribution of which differed from normal in two related groups, the Wilcoxon criterion was used. The null statistical hypothesis about the absence of differences and connections was rejected at p&amp;lt;0.05. Results among the examined patients there were 61 men (93.8%), 4 women (6.2%). The average age of men was 39.0±8.2 years, women - 34.7±9.7 years. The duration of the underlying disease at the time of inclusion in the study was 55.98 [40.67-71.28] months. 57 people (85.1%) received ACE inhibitors/sartans in therapeutic doses as the main therapy, 8 people (11.9%) did not receive drug therapy. It was possible to evaluate the effectiveness of GFD in patients from group 1 in 9 people. During the follow-up period, 2 patients from group 1 showed progression of the disease to the End-Stage Renal Disease (GFR according to CKD-EPI &amp;lt;15 ml/min/1.73 m2), which required their exclusion from the study, in 2 more patients it was not possible to evaluate the effectiveness of GFD due to insufficient follow-up periods (less than 6 months.) GFD was also recommended to patients from group 2. Dietary restrictions were applied to patients with daily protein loss &amp;gt; 0.5 g/day and/or anti-TTG IgA and anti-DPG IgA levels in the range of pre-reference values, thus it was possible to evaluate the effectiveness of GFD in patients of group 2 in 21 people. According to the results of the analysis, a statistically significant decrease in daily proteinuria (p = 0.028) and microscopic hematuria (p = 0.018) was revealed. After 6 months from the start of compliance with GFD, daily proteinuria decreased in 66.7%; microscopic hematuria – in 77.8% in group 1 patients. Among group 2 patients, a statistically significant decrease in microscopic hematuria (p = 0.05) was observed in 76.2% of those included in the study. Conclusion the inclusion of GFD in the diet of patients with IgAN is justified in patients with the presence of gluten antibodies in the blood serum, as it allows to significantly reduce the severity of proteinuria, microscopic hematuria in these patients. Screening examination of patients with IgAN for gluten metabolism disorders will expand therapeutic possibilities, and GFD can become part of a nephroprotective strategy.

Celiac Disease in Children: A 2023 Update.

Celiac disease (CeD) is a chronic immune-mediated enteropathy, which occurs in genetically predisposed individuals by the ingestion of gluten proteins present in wheat, barley and rye. The global pooled prevalence of CeD is 0.7% and it has been reported from nations all around the globe and can affect individuals of any age. It has a wide clinical spectrum ranging from being asymptomatic to being symptomatic with severe manifestations. Though initial descriptions of CeD focused on the classical presentation with gastrointestinal manifestations, in recent years it has been found that more patients have non-classical manifestations such as anemia, osteoporosis, increased transaminases, failure to thrive or short stature.The definitive diagnosis of CeD is based on a combination of clinical history, serologic testing with/without examination of duodenal biopsies. The preferred initial serologic test regardless of age for the detection of CeD is the tissue transglutaminase (IgA anti-tTG). Children with a high tTG-IgA (≥10 ULN) AND a positive anti-endomysial IgA antibody (EMA) can be diagnosed to have CeD without the need for duodenal biopsies. The rest should undergo biopsies with at least 4 biopsies from the distal duodenum and at least 1 from the bulb. A correctly orientated biopsy showing increased intraepithelial cells and a villous to crypt ratio of <2 is suggestive of CeD. The management of CeD is a lifelong complete dietary avoidance of gluten. IgA-TGA acts as a surrogate marker for healing of the small-bowel mucosa and should be performed every 6 mo until normalization and then every 12-24 mo thereafter.

The Characteristics of Isolated Bulb Celiac Disease in Children.

Mucosal injury in celiac disease (CD) patients can be patchy, and up to 12% of CD patients can have mucosal changes limited to the duodenal bulb. Hence, recent guidelines recommend obtaining bulb biopsies in addition to distal duodenum. This study aimed to describe a cohort of children with isolated bulb CD and assess the benefit of separating bulb biopsies. A retrospective chart review between January 2011 and January 2022 at 2 medical centers was conducted. We included children with CD who underwent endoscopy with separated biopsies from the bulb and distal duodenum. A blinded pathologist performed Marsh-Oberhuber grading on selected cases. We identified 224 CD patients, of which 33 (15%) had histologically confirmed isolated bulb CD. Patients with isolated bulb CD were older at diagnosis (10 vs 8 years; P = 0.03). Median anti-tissue transglutaminase immunoglobulin A (TTG IgA) level was lower in isolate bulb CD (2.8 vs 16.7 times the upper limit of normal [ULN], P < 0.001). Almost 88% (29/33) of isolated bulb CD patients had an anti-TTG IgA value of less than 10 times the ULN. Time to anti-TTG IgA normalization (mean 14 months) was similar between the 2 groups. A pathologist review of diagnostic biopsies could not distinguish between the bulb and distal duodenum biopsies in approximately one-third of the reviewed samples. Separating bulb from distal duodenum biopsies can be considered during CD diagnosis, particularly in children with anti-TTG IgA levels less than 10 times the ULN. Larger prospective cohorts are needed to decide whether isolated bulb CD is a unique cohort or an early stage of the conventional CD.

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.

Study of the immune response in celiac patients with selective IgA deficiency who start a gluten-free diet.

Studies are scarce regarding IgG anti-tissue transglutaminase 2 (tTG) normalization in selective IgA deficient (SIgAD) celiac disease (CD) patients after beginning a gluten free diet (GFD). The aim of this study is to analyse the decreasing dynamics of IgG anti-tTG in patients diagnosed with CD who start a GFD. To achieve this objective, IgG and IgA anti-tTG levels at diagnosis and during follow-up in 11 SIgAD CD patients and in 20 IgA competent CD patients were retrospectively evaluated. At diagnosis, statistical differences were not found when comparing IgA anti-tTG levels of IgA competent subjects with IgG anti-tTG levels of SIgAD subjects. Regarding the decreasing dynamics, even though no statistical differences were found (p = 0.06), normalization rates were slower for SIgAD CD patients. After 1 and 2years on GFD, respectively, only 18.2% and 36.3% of the SIgAD CD patients normalized IgG anti-tTG levels; otherwise, IgA anti-tTG reached values under the reference values in 30% and 80% of the IgA competent patients in the same time-points. Although IgG anti-tTG has demonstrated a high diagnostic efficiency in SIgAD CD pediatric patients, this test does not appear to be as precise for long-term GFD response monitoring as IgA anti-tTG levels in IgA sufficient patients.