Anti-tissue Transglutaminase Antibodies Research Articles

Meta-Analysis: Global Prevalence of Coeliac Disease in Type 1 Diabetes.

Coeliac disease (CD) is common in patients with type 1 diabetes (T1D), but prevalence varies globally due to differing screening protocols. There have been substantial changes in screening guidelines over the past two decades. To evaluate CD prevalence in patients with T1D, focusing on screening studies using antitissue transglutaminase (anti-tTG) antibody. We searched PubMed, Web of Science, Embase and Scopus for studies published up to 11 December 2023 using keywords related to CD and diabetes. We used random-effects models for overall prevalence and all subgroups, with heterogeneity assessed using Cochran's Q test and the I2 statistic performed in STATA 18. We included 106 articles involving 65,102 T1D patients across 40 countries. The pooled CD seroprevalence and confirmed CD prevalence were 9% (95% confidence interval, CI, 8%-10%) and 6% (95% CI 5%-7%), respectively. The prevalence was higher in females and children. Denmark, Saudi Arabia and Libya exhibited the highest prevalence (11%), followed by India and Egypt (10%). Belgium, France, Germany, South Africa and the United States had the lowest prevalence (2%). High-income countries showed significantly a lower CD prevalence than middle-income countries (p = 0.03). Meta-regression based on the Human Development Index (HDI) indicated that countries with higher HDI have lower seroprevalence and confirmed CD prevalence. Approximately 1 in 16 patients globally and 1 in 12 patients in Asia and the Middle East with T1D has CD. We suggest that all patients with T1D should be screened for CD.

Prevalence of Celiac Disease in Patients with Nutritional Anemia in Western Part of India.

Background: Around 1.6 billion people worldwide are affected by nutritional anemia. A small percentage of nutritional anemia cases are attributed to celiac disease (CeD). However, data on the prevalence of CeD among individuals with nutritional anemia in the Western part of India is scarce. Patients and methods: Individuals with nutritional anemia were prospectively investigated for the presence of CeD through the detection of immunoglobulin A (IgA) antitissue transglutaminase antibodies (anti-tTG Ab). Those who had a positive antibody result proceeded to have an upper gastrointestinal endoscopy, accompanied by a duodenal biopsy. The diagnosis of CeD was confirmed following Indian guidelines. Results: A total of 116 patients, including 96 females, were screened, with a mean age of 37 ± 17.8 years. Among them, 19 patients (16.3%) were positive for IgA anti-tTG antibodies. Fifteen of these antibody-positive patients agreed to undergo a duodenal biopsy, which showed villous abnormalities of modified Marsh grade 2 or higher in 11 cases. The overall seroprevalence of CeD was 16.3%, while the biopsy-confirmed prevalence stood at 9.3%. Moreover, an additional four patients (3.4%) were identified as having potential CeD. Chronic diarrhea and short stature emerged as significant predictors of CeD among patients with nutritional anemia. Conclusion: Even in the Western part of India, approximately one in 10 patients with nutritional anemia have CeD, reflecting similar findings across the country. Consequently, we should screen all patients with nutritional anemia for CeD through antitissue transglutaminase antibody testing. This is especially crucial for those with unexplained, persistent nutritional anemia that does not respond to oral iron therapy.

Anti-tissue transglutaminase antibody correlation with severity of villous abnormalities in celiac disease: A Systematic Review and Meta-analysis

Abstract Introduction/Objective Celiac disease (CD) is a long-term autoimmune disorder that affects individuals genetically predisposed to gluten intolerance. Biomarkers, particularly anti-tissue transglutaminase antibody (anti-tTG ab), are crucial in indicating disease states and have potential as non-invasive substitutes for mucosal biopsies in assessing the severity of intestinal damage. This study aims to systematically review and analyze the correlation between anti- tTG antibody levels and the severity of villous abnormalities in patients with celiac disease to evaluate the potential of anti-tTG as a non-invasive diagnostic tool. Methods/Case Report Following PRISMA guidelines, a comprehensive literature search selected 15 studies focusing on the correlation between anti-tTG antibodies and villous atrophy. Systematic data extraction and quality assessments were performed, followed by statistical analyses to determine the strength and consistency of associations. Results (if a Case Study enter NA) Analysis of data from four studies on anti-tTG antibody positivity revealed a nearly significant pooled effect size (p = 0.06) with considerable heterogeneity (I^2 = 97%, p < 0.00001). Additionally, data from five studies using the MARSH classification of histological damage, aggregated using a random-effects model, showed overall statistical significance (Z = 3.36, p = 0.0008). Conclusion Anti-tTG antibodies serve as a reliable indicator of villous damage in CD, supporting their dual utility in diagnosis and monitoring. High anti-tTG antibody titers could potentially eliminate the need for invasive biopsy procedures in certain patient subsets, underscoring the promise of more refined and non-invasive diagnostic approaches, although further research is needed to address the implications of high heterogeneity observed in the studies.

6771 New onset Graves’ Disease in a Patient with Hashimoto's Thyroiditis and Positive Thyroid Peroxidase Autoantibodies. Case Report

Abstract Disclosure: M.M. Eid: None. J.L. Zapater: None. Introduction: Hashimoto’s Thyroiditis (HT) and Graves’ Disease (GD) are the most common thyroid autoimmune disorders. Transition of GD to HT is common, but transition of HT to GD is rare. Case: A 55 year old, female with depression, HTN and fibromyalgia. She was referred for evaluation of chronic fatigue and reduction in functional capacity. Five years earlier, she had also been evaluated for fatigue. Labs at that time: TSH 3.80 µIU/ml (0.35-3.74 µIU/ml), free T4 0.8 ng/dl (0.76-1.46 ng/dl), thyroid peroxidase antibody (anti-TPO) 605.6 U/ml (0-60 U/ml), and anti-thyroglobulin antibody (anti-TG) 37.2 U/ml (0-60 U/ml). Subclinical hypothyroidism was diagnosed, but no levothyroxine was initiated. Her TSH was found to be normal in 2019 and 2021. At the current clinical encounter, other than fatigue she denies weight/voice change, tremor, palpitation, anxiety, recent flu like illness or radiation exposure, neck swelling/pain, heat intolerance, or difficulty swallowing. Her daily medications are amlodipine 10mg and duloxetine 20mg. She had menopause 2 years ago. She has no known allergy. She has a brother with rheumatoid arthritis. She denies smoking or alcohol consumption. On exam, vital signs are normal, and BMI is 28.1. There is diffuse, firm thyromegaly without a palpable nodule. There is no cervical lymphadenopathy, tremor, neck tenderness, exophthalmos, or lid lag. Creatinine, liver enzymes are normal but hemoglobin is 9gm/dl. Anti-tissue transglutaminase and anti-gliadin antibodies were negative. Her thyroid labs were: TSH <0.008 uIU/ml, free T4 1.06ng/dl, free T3 4.07 pg/ml (2.3-4.2 pg/ml), total T3 1.74 ng/ml (0.60-1.81 ng/ml), anti-TPO antibody 12,414 U/ml, anti-TG antibody 22 U/ml, thyrotropin receptor antibody (TRAB) 15.24 IU/L (0-1.75 IU/L), and thyroid stimulating immunoglobulin (TSI) 331% (<130%). Thyroid uptake scan showed 49% iodine-131 uptake in symmetric and homogenous uptake, and no hot or cold nodules. GD was diagnosed, methimazole 5mg daily was initiated. Conclusion: Our case had subclinical HT with positive anti-TPO antibodies 5 years preceding the onset of GD. Causes of autoimmune conversion are not well understood. Viral infection or radiation exposure in genetic susceptible patients have been assumed as triggers (1). The blocking and stimulating action of TRAB on TSH receptors is considered as a possible mechanism of switching between hypothyroidism and hyperthyroidism. Clinical and biochemical evaluation for possible conversion to GD in patients with HT is recommended (2).

Diagnostic Yield of the Number of Duodenal Biopsies in Celiac Disease

Abstract Background The diagnosis of celiac disease relies on a combination of clinical evaluation, serological testing, and histopathological examination of duodenal biopsies. However, there is ongoing debate regarding the optimal number of duodenal biopsies required for an accurate diagnosis, as well as the isolated yield of water interface directed biopsy. Aim The primary objective is to determine the cumulative benefit of multiple duodenal biopsies, establishing the specificity and sensitivity of each biopsy separately with focus on the isolated yield of water interface directed biopsy. Methods A Cross-sectional study conducted on 22 children with symptoms and signs suggestive of celiac disease (CD) and positive serology with antitissue transglutaminase antibodies at the pediatric gastrointestinal endoscopy Unit at EL Demerdash Hospital, Ain Shams University for 6 months. four biopsies were taken, one from duodenal bulb, and 2 from rest of duodenum and the fourth one using water immersion technique visualizing the most affected area. Results Among the 22 enrolled children, 18 patients were histopathologically positive for celiac disease and 4 children were negative. The bulb, duodenal, and water interface biopsies were positive in 94.4%, 88.8%, and 66.7% respectively, of those positively diagnosed as celiac disease by Marsh criteria. In addition, bulb, and duodenal biopsies have the highest sensitivity of 94.4%, and 88.9%, respectively, also, they have the highest accuracy. Duodenal bulb biopsies were capable alone to diagnose 17 out of 18 definite cases. The missed case diagnosis was reached either by water interface or any random duodenal biopsy. Conclusion Bulb biopsy showed to be the most accurate in diagnosing celiac disease, on the contrary, water interface biopsy was not sensitive in diagnoses, so the celiac diagnostic efficacy can be reached by assessment of 2 duodenal biopsies, one of them from the duodenal bulb.

Electrochemical detection of anti-tissue transglutaminase antibody using quantum dots-doped polypyrrole-modified electrode

A nanohybrid-modified glassy carbon electrode based on conducting polypyrrole doped with carbon quantum dots (QDs) was developed and used for the electrochemical detection of anti-tissue transglutaminase (anti-tTG) antibodies. To improve the polypyrrole conductivity, carrier mobility, and carrier concentration, four types of carbon nanoparticles were tested. Furthermore, a polypyrrole-modified electrode doped with QDs was functionalized with a PAMAM dendrimer and transglutaminase 2 protein by cross-linking with N-hydroxysuccinimide (NHS)/N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (EDC). The steps of electrode surface modification were surveyed via electrochemical measurements (differential pulse voltammetry (DPV), impedance spectroscopy, and X-ray photoelectron spectroscopy (XPS)). The surface characteristics were observed by scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, and contact angle measurements. The obtained modified electrode exhibited good stability and repeatability. DPV between − 0.1 and 0.6 V (vs. Ag/AgCl 3 M KCl reference electrode) was used to evaluate the electrochemical alterations that occur after the antibody interacts with the antigen (transglutaminase 2 protein), for which the limit of detection was 0.79 U/mL. Without the use of a secondary label, (anti-tTG) antibodies may be detected at low concentrations because of these modified electrode features.Graphical

Development and Validation of a Tool for Assessing Adherence to Gluten-Free Diet in Patients With Celiac Disease.

Life-long adherence to gluten-free diet (GFD) and its assessment is essential for patients with celiac disease (CeD). We have developed and validated a tool for assessing adherence to GFD which can be used by both physicians and dietitians. Phase 1: Development, content validation, and assessment of reliability of tool. Phase 2: Validation of tool against standard dietary evaluation (SDE) (gold standard), immunoglobulin A - anti-tissue transglutaminase antibodies (IgA anti-tTG Ab), and gluten immunogenic peptides in urine. Overall, 380 biopsy-confirmed patients with CeD (derivation cohort: n = 100 [phase 1], n = 210 [phase 2] and independent validation cohort, n = 70) were recruited. Of an initial 90-point questionnaire, 84 items (Celiac Disease: Compliance Assessment Test [CD-CAT.v1]) were retained after content validation and pilot testing. In phase 1, upon administering CD-CAT.v1 on 100 patients, a comprehensive 35-item tool (CD-CAT.v2; α = 0.86) was obtained after removing items with low test-retest reliability and item-rest correlation values. In phase 2, upon administering CD-CAT.v2 on 210 patients, 22 items were removed having low correlation values (R < 0.4) with SDE. Finally, a 13-item tool (CD-CAT.v3; α = 0.84) was obtained with high criterion validity with SDE ( r = 0.806, P < 0.001), moderate convergent validity with celiac disease adherence test ( r = 0.602, P = 0.007), and moderate to weak correlation with urine gluten immunogenic peptides ( r = 0.46, P = 0.001) and IgA anti-tTG Ab ( r = 0.39, P = 0.008), respectively. The final 13-item tool also strongly correlated with SDE ( r = 0.78, P < 0.001) in an independent validation cohort of 70 patients with CeD. Principal component analysis identified 3 relevant subscales with a cumulative variance of 62%. The sensitivity and specificity of CD-CAT.v3 were 80% and 91%, respectively, with an area under curve of 0.905 with SDE. The obtained cutoff score of <19 from the receiver operating characteristic curve was further categorized as 13 = excellent, 14-18 = very good, 19-28 = average, and >28 = poor adherence to GFD. CD-CAT is a new and rapid tool for monitoring dietary adherence to GFD with high sensitivity and specificity, which can be administered by both physicians and dietitians.

Potential Celiac Disease in Children: Health Status on A Long-Term Gluten-Containing Diet.

Potential celiac disease (PCD) is a clinical condition characterised by the presence of a positive CD-specific serology and a normal intestinal architecture. Asymptomatic PCD patients are generally advised to continue on a gluten-containing diet (GCD), but long-term risks of this approach have never been explored. In the present study, we aimed to investigate nutritional and autoimmune complications possibly developing overtime in a cohort of asymptomatic PCD children on a GCD. We compared children's parameters of growth, nutritional status, and autoimmunity between the time of diagnosis and on the occasion of their last medical check, after a long-term gluten-containing diet. Altogether, we collected data from 171 PCD children with a mean follow-up time of 3 years (range 0.35-15.3 years). During follow-up, although patients did not reduce their amount of daily gluten intake, their anti-tissue transglutaminase (anti-TG2) antibodies spontaneously and significantly decreased. Most parameters analysed had not changed during follow-up (height centile, ferritin, albumin, cholesterol, calcium, alkaline phosphatase, parathormone, and vitamin D) or even improved significantly (weight and BMI centile, haemoglobin, blood iron, HDL, glycaemia, and HbA1C, p < 0.05), always remaining within the limit of normality. Equally, autoantibodies for other concomitant autoimmune disorders did not increase overtime. Similar results were obtained excluding from analysis patients who had stopped producing anti-TG2 and those with a follow-up time < 3 years. Our pilot study has provided reassuring results regarding the maintenance of a gluten-containing diet in asymptomatic PCD children, even when long-term follow-up was considered.

Recent Trends in Seroprevalence of Celiac Disease at a Tertiary Care Center.

It is a retrospective study and all samples received in the laboratory from symptomatic patients for estimation of Immunoglobulin A (IgA) antitissue transglutaminase (IgA anti-tTGA) antibodies are included. Seroprevalence of celiac disease was determined using indirect enzyme-linked immunosorbent assay for IgA anti-tTGA. Out of 8787 serum samples received in the laboratory over a period of four years, the seroprevalence of CD was 2.1, 1.62, 0.72, and 3.3%, respectively.

Maintaining a gluten-free diet is associated with quality of life in youths with type 1 diabetes and celiac disease

AimConflicting findings have been reported on whether in youths, the double diagnosis of type 1 diabetes (T1D) and celiac disease (CD) substantially impacts quality of life QoL, compared to subjects with T1D only.MethodsIn this study, 86 youths with double diagnosis and their parents were compared to 167 subjects with T1D only. QoL was assessed through the KINDL questionnaire. Anti-tissue transglutaminase antibodies and dietary interviews evaluated the degree of maintaining a gluten-free diet (GFD).ResultsWe found that having CD in addition to T1D has little effect on overall QoL. However, analysis of the degree of maintaining GFD revealed significantly lower total QoL scores in groups with T1D + CD not strictly maintaining GFD compared to T1D only (p = 0.0014). The multivariable linear regression model confirmed the importance of maintaining GFD on QoL in subjects (p = 0.0066) and parents (p = 0.023).ConclusionThe coexistence of T1D and CD and the adoption of a GFD resulted in poor QoL levels, as in youth as in their parents, when difficulties implementing the GFD are present. Psychological support should consider the importance of maintaining GFD not only to prevent potential complications in the future but also to improve actual QoL in different subdomains.

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.

Maintaining the gluten-free diet: the key to improve glycemic metrics in youths with Type 1 Diabetes and Celiac Disease

AimsGluten-free diets (GFD) were considered as high glycemic index and/or high content of saturated fats; this could affect keeping good metabolic control in individuals with both type 1 diabetes (T1D) and celiac disease (CD). Our objective was to analyze time in range and other continuous glucose monitoring (CGM) metrics with real-time CGM systems, in youths with T1D and CD, compared to those with T1D only. Methodsan observational case-control study, comparing youths aged 8-18 years with T1D and CD, with people with T1D only was performed. The degree of maintaining GFD was assessed through anti-tissue transglutaminase antibodies and dietary interview, and maintaining Mediterranean diet through the KIDMED questionnaire. Results86 youths with T1D and CD, 167 controls with T1D only, were included in the study and the two groups reported similar real-time CGM metrics. Among the first group, 29% were not completely maintaining GFD and compared to people with T1D only they showed higher hyperglycemia rates (% time above range: 38.72±20.94 vs 34.34±20.94; P = 0.039). ConclusionsIndividuals with T1D and CD who maintain GFD presented similar glucose metrics compared to youths with T1D only. Individuals not strictly maintaining GFD presented higher hyperglycemia rates.

Vitamin D and celiac disease.

Celiac disease (CD) is an immune-mediated condition affecting the small intestine. Its reported global prevalence falls within the range of 0.7% to 1.4%. Notably, historically, higher rates, reaching 1% in Western Ireland, have been documented. Recent research has even revealed prevalence rates as elevated as 2% in northern Europe. These findings underscore the urgency for swift and cost-effective diagnosis, especially in individuals identified through screening efforts. At present, the diagnosis of CD relies on a multifaceted approach involving positive serological markers such as IgA anti-tissue transglutaminase (anti-TTG) and anti-endomysial antibodies (anti-EMA). These serological findings are assessed in conjunction with classical histological alterations, as outlined in the Marsh classification. CD is an inflammatory condition triggered by the consumption of gluten, resulting from intricate interactions between genetic, immunological, and environmental factors. CD is linked to malabsorption, leading to nutritional deficiencies. Individuals with CD are required to adhere to a gluten-free diet, which itself can lead to nutrient deficiencies. One such deficiency includes vitamin D, and there is substantial experimental evidence supporting the notion of a bidirectional relationship between CD and vitamin D status. A low level of vitamin D has a detrimental impact on the clinical course of the disease. Here we summarize the key characteristics of CD and explore the prominent roles of vitamin D in individuals with CD.

Осведомленность врачей в Узбекистане о целиакии: исследование на основе анкетирования

Objective. To assess the level of awareness of celiac disease, its timely diagnosis and effective treatment among primary care and hospital physicians. Patients and methods. A total of 207 physicians from the Republic of Uzbekistan participated in the study. The questionnaire included 17 questions about clinical manifestations, diagnosis, identification of risk groups and treatment of celiac disease. Results. Only 31.9% of respondents were aware of the autoimmune mechanism of celiac disease. More than 71% of physicians, especially primary care, know well about the typical manifestations of celiac disease (diarrhea, underweight), but quite rarely consider constipation (25.1%), abdominal pain of unknown etiology (46.9%), common colds (24.6%) as a manifestation of celiac disease. Low awareness of the association of celiac disease with autoimmune thyroiditis (20.8%), type 1 diabetes (14.9%), and infertility (34.3%) was shown. Only 43.9% of physicians use to anti-tissue transglutaminase antibodies as serological markers of celiac disease, 30.9% continue to focus on anti-gliadin antibodies. Only 32.9% of patients with suspected celiac disease are referred to a gastroenterologist for evaluation. Conclusion. The results of the study demonstrate a rather low level of awareness of clinical manifestations, methods of diagnosis and treatment of celiac disease among physicians in the Republic of Uzbekistan. It is necessary to develop additional educational programs and introduce modern research methods, especially in remote regions of the country, for timely diagnosis and treatment of celiac disease. Key words: celiac disease, diagnosis, treatment, physicians, survey

The Correlation Between Serum Anti-tissue Transglutaminase (Anti-tTG) Antibody Levels and Histological Severity of Celiac Disease in Adolescents and Adults: A Meta-Analysis.

Celiac disease is an autoimmune disorder characterized by a broad spectrum of histological damage to the intestinal mucosa. Comprehension and understanding of the association between anti-tissue transglutaminase (anti-tTG) antibody levels and the histological severity of celiac disease are not well established, prompting the need for meta-analysis. This study aims to offer insights into the diagnostic abilities of anti-tTG antibody levels in determining the histological severity of celiac disease by providing quantitative evidence based on a diverse range of studies. An extensive search was conducted across four electronic research databases to identify primary research articles reporting serum anti-tTG antibody levels in correlation with different Marsh grades, signifying the histological severity of celiac disease. The software tool RevMan 5.4 (the Cochrane Collaboration, London, UK) was used to compile standardized mean differences (SMD) alongside their respective confidence intervals. A total of 13 studies were included in the meta-analysis, with a patient pool of 2505 patients. Marsh grade I and II were found to have higher anti-tTG antibody levels compared to those with grade 0 (SMD 1.50; 95% CI: 1.12, 1.87; p-value <0.00001). Antibody levels were higher in Marsh grade IIIa when compared to both grade 0 (SMD 0.97; 95% CI: 0.67, 1.28; p-value <0.00001) and grade ≤2 (SMD 0.61; 95% CI: 0.44, 0.79; p-value <0.00001). Patients with Marsh IIIb also reported greater anti-tTG levels compared to grade 0(SMD 1.48; 95% CI: 0.99, 1.96; p-value <0.00001) and grade ≤2 (SMD 0.98; 95% CI: 0.79, 1.18; p-value <0.00001). Likewise, Marsh grade ≥IIIc reported high levels of anti-tTG antibodies in comparison with grade 0 (SMD 1.06; 95% CI: 0.72, 1.39; p-value <0.00001) and grade ≤2 (SMD 1.18; 95% CI: 1.02, 1.34; p-value <0.00001). Our meta-analysis revealed a consistent, robust correlation between anti-tTG antibody levels and the histological severity of celiac disease, with a clear trend of increasing antibody levels corresponding to the severity of mucosal damage. Large-scale primary research initiatives are needed to reach definitive conclusions.

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.

SAT580 Incidental Diagnosis Of Genetic Variant PTPN11 Noonan Syndrome With Multiple Lentigines, Sensorineural Hearing Loss And Rheumatoid Arthritis In Adult Female With Hashimoto’s Thyroiditis. Case Report

Abstract Disclosure: M.M. Eid: None. T. Zahra: None. J. Vargas-Jerez: None. Introduction: Hashimoto’s thyroiditis (HT, chronic lymphocytic thyroiditis, autoimmune thyroiditis) and Rheumatoid arthritis (RA) are autoimmune disorders, affect mainly females (1). Noonan syndrome with Multiple Lentigines (NSML, Leopard Syndrome) is a rare multigenetic autosomal dominant disorder. It includes cerebrovascular and cardiac anomalies, facial phenotype, hearing abnormality and developmental delay (2). Case: 41 yo, Female with history of HT since 2002 (high TSH, thyroid peroxidase antibody more than 1000 u/ml, low FT4 and FT3) on levothyroxine 150mcg/day. Recently moved to the USA from EL Salvador. Presented for initial evaluation. Denied smoking, alcohol, allergy. Maternal aunt with thyroid disease. Had menstrual irregularities, no previous attempt to conceive. Review of system: 5 months of pain, swelling and morning stiffness for 1 hour in hand joints, hearing difficulty for 2 years, painless brown skin spots for years, childhood learning difficulty and constipation. Physical examination body weight 139Ib, height 162cm, Stable vitals, diffuse lentigines. Head: board forehead, hypertelorism, high arched eye brows, micrognathia, low set ears. Heart: normal heart sounds, no murmur. No thyromegaly, nystagmus or vertigo. Hand: swelling of metacarpophalangeal and proximal interphalangeal joints. Laboratory work up TSH 8 normal 0.27 to 4.2 uIU/ml, FT4 0.8 normal 0.9-1.8 ng/dl, A1C 5.7, positive rheumatoid factor 199IU/ml, anti-CCP antibody &amp;gt; 250U, ANA 1/320, ESR 61ml/hr, negative anti-tissue transglutaminase antibody, normal liver and kidney function tests and complete blood count. Hand X-ray: decrease joint space and bone erosion. Thyroid US: normal size, vascularity, no nodule. Normal Echocardiogram, EKG and chest X ray. Internal auditory canal MRI: no masses or abnormal enhancement. DEXA Scan: osteopenia of femur and lumbar spine. She was diagnosed with seropositive RA, B/L sensorineural hearing loss (SNHL) more on right side. Genetic test revealed heterozygous pathogenic variant of PTPN11 gene consistent with NSML and negative for Neurofibromatosis type 1. Kept on prednisone and methotrexate, levothyroxine was increased 162mcg/day. Conclusion: Autoimmune disorders have a common pathogenesis including humoral and cell mediated immunity, autoimmune oxidative stress, UV radiation exposure, genetic linkage and biochemical changes. Diagnosis of one autoimmune disorder increases the possibility of other autoimmune disorders (1). NSML has a variable presentation. PTPN11-NSML is usually associated with SNHL and cardiac anomalies as pulmonary stenosis. It is infrequent to diagnose NSML with HT and structurally normal heart like our case(2).

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.