Screening For Celiac Disease Research Articles

Celiac Disease Frequency Is Increased in IgE-Mediated Food Allergy and Could Affect Allergy Severity and Resolution.

An increased frequency of celiac disease (CeD) has been reported in severe Immunoglobulin E (IgE) -mediated food allergy (FA). This observation requires confirmation, and whether CeD affects FA severity and resolution is unknown. The study aims to estimate the prevalence of CeD in patients with FA and to investigate whether CeD affects FA severity and oral tolerance. Consecutive patients with FA referred for allergen reintroduction, either to evaluate allergy resolution or to start oral immunotherapy (OIT), were evaluated for CeD and for FA severity. The primary outcome was the prevalence of CeD. Secondary outcomes were the frequency of severe FA and the level of clinical tolerance at study entry and at last follow-up in patients with isolated FA versus patients with FA + CeD. Two hundred twenty-eight patients were included. CeD was confirmed in 15 patients (6.6%) of whom, 8 patients had a previously established diagnosis of CeD and were on a gluten-free diet. Severe FA was observed in 12 patients with FA + CeD (80%) versus 88 patients with FA (42%) ( P = 0.006). At baseline, patients with FA + CeD had significantly higher median allergen-specific IgE levels [61.8 kU/L; interquartile range (IQR) 11.6-279.0] compared to patients with FA (20.3 kU/L; IQR 2.9-72.7) ( P < 0.001). Complete clinical tolerance was observed in 1 of 15 patients (7%) with FA + CeD versus 98 of 205 patients (48%) with FA ( P = 0.002). CeD is highly prevalent in patients with FA and could affect FA severity and response to OIT. CeD screening should be considered in patients with severe or persistent FA.

Who to screen and how to screen for celiac disease

Celiac disease (CeD) is a chronic gluten-induced enteropathy with plethoric manifestations. The typical manifestations of CeD such as chronic diarrhea and malabsorption are widely recognized, however, many patients have atypical manifestations like iron deficiency anemia, idiopathic short stature, hypertransaminesemia or infertility, etc. These patients often present to the primary care physicians and/or non-gastrointestinal specialties. However, due to a lack of awareness among the healthcare professionals about the various atypical manifestations, many patients are not screened for CeD. In this review, we have summarized the available literature about the prevalence of CeD in various gastrointestinal (chronic diarrhea) and non-gastrointestinal conditions (iron deficiency anemia, short stature, cryptogenic hypertransaminesemia, cryptogenic cirrhosis or idiopathic ataxia etc.) where the diagnosis of CeD should be con-sidered. In addition, we also discuss special scenarios where screening for CeD should be considered even in absence of symptoms such as patients with type 1 diabetes, Down’s syndrome, and first-degree relatives of patients with CeD. Further, we discuss the diagnostic performance and limitations of various screening tests for CeD such as IgA anti-tissue transglutaminase antibodies, anti-endomysial antibodies and anti-deamidated gliadin antibodies. Based on the current recommendations, we propose a diagnostic algorithm for patients with suspected CeD.

EP-180 Analysis of two-week wait referrals to a colorectal surgery department for iron deficiency anaemia in a rural DGH

Abstract Iron deficiency anaemia (IDA), defined as low haemoglobin and ferritin levels, affects 2–5% of adults in the developed world. Asymptomatic malignant gastrointestinal pathology must be excluded in all patients. Patients referred on a two-week wait Colorectal pathway with IDA between 4/1/2018–28/2/2021 were recruited (n=566). 92.4% of patients were investigated, only 45.2% had true IDA. Although screening for coeliac disease was a prerequisite in the referral pro forma, 63.2% were referred without. NICE guidance recommends upper and lower gastrointestinal investigations in all patients with confirmed IDA. 61.6% of patients had both investigations performed. 65.1% patients were diagnosed with benign conditions- diverticular disease (37.6%), polyp (31%) and hiatus hernia (28.5%). Age was the strongest predictor for pathology in patients with IDA (p=0.001), not specifically for cancer (p=0.111). 4.4% (n=23) patients were diagnosed with colorectal cancer. Low haemoglobin was significantly correlated with cancer (p=0.002), however only 60.9% had low ferritin. Guidelines suggest that only post-menopausal women should be investigated for IDA unless symptomatic or risk factors. Although only 80% had symptoms; the entire cohort had investigations and only 60% returned a positive test. This study highlighted variability in investigations in addition to lack of adherence by primary care physicians to referral guidelines resulting in avoidable referrals and potentially inappropriate investigations in pre-menopausal women by secondary care physicians, thus overwhelming an exceedingly burdened two- week wait pathway.

Sources of dietary gluten in the first 2 years of life and associations with celiac disease autoimmunity and celiac disease in Swedish genetically predisposed children: The Environmental Determinants of Diabetes in the Young (TEDDY) study

ABSTRACTBackgroundHigh gluten intake is associated with increased risk of celiac disease (CD) in children at genetic risk.ObjectivesWe aimed to investigate if different dietary gluten sources up to age 2 y confer different risks of celiac disease autoimmunity (CDA) and CD in children at genetic risk.MethodsThree-day food records were collected at ages 6, 9, 12, 18, and 24 mo from 2088 Swedish genetically at-risk children participating in a 15-y follow-up cohort study on type 1 diabetes and CD. Screening for CD was performed with tissue transglutaminase autoantibodies (tTGA). The primary outcome was CDA, defined as persistent tTGA positivity. The secondary outcome was CD, defined as having a biopsy specimen showing Marsh score ≥ 2 or an averaged tTGA level ≥ 100 Units. Cox regression adjusted for total gluten intake estimated HRs with 95% CIs for daily intake of gluten sources.ResultsDuring follow-up, 487 (23.3%) children developed CDA and 242 (11.6%) developed CD. Daily intake of ≤158 g porridge at age 9 mo was associated with increased risk of CDA (HR: 1.53; 95% CI: 1.05, 2.23; P = 0.026) compared with no intake. A high daily bread intake (>18.3 g) at age 12 mo was associated with increased risk of both CDA (HR: 1.47; 95% CI: 1.05, 2.05; P = 0.023) and CD (HR: 1.79; 95% CI: 1.10, 2.91; P = 0.019) compared with no intake. At age 18 mo, milk cereal drink was associated with an increased risk of CD (HR: 1.16; 95% CI: 1.00, 1.33; P = 0.047) per 200-g/d increased intake. No association was found for other gluten sources up to age 24 mo and risk of CDA or CD.ConclusionsHigh daily intakes of bread at age 12 mo and of milk cereal drink during the second year of life are associated with increased risk of both CDA and CD in genetically at-risk children.

Population-based screening for celiac disease reveals that the majority of patients are undiagnosed and improve on a gluten-free diet

The impact of a gluten-free diet (GFD) on screen-detected celiac disease (CD) is currently ambiguous. We aimed to identify the population-based prevalence of undiagnosed adult CD and examine the impact of a GFD on screen-detected CD. In total, 12,981 adults participated in a population-based health study in Tromsø, Norway. Participants with increased levels of anti-tissue transglutaminase-2 IgA or anti-deamidated gliadin peptide IgG were invited to undergo gastroduodenoscopy with both histological and immunohistochemical examination of small-bowel biopsies. The prevalence of previously diagnosed CD was 0.37%. Additionally, the prevalence of previously undiagnosed CD was 1.10%. Thus, 1.47% of the population had CD, of whom 75% were previously undiagnosed. A GFD resulted in significant improvements in overall gastrointestinal symptoms, diarrhea, and health-related quality of life, with reduced abdominal discomfort (76%) and improved levels of energy (58%). The large majority of patients with adult CD were undiagnosed and benefited from a GFD with reduced gastrointestinal symptoms and improved health-related quality of life. In clinical practice, there should be a low threshold for CD testing even in the absence of abdominal complaints because most adult patients appear to consider their symptoms a part of their normal state and therefore remain untested and undiagnosed.Trial registration: Clinical Trials. Gov Identifier: NCT01695681.

Screening of gastrointestinal symptoms and celiac disease in children with autism spectrum disorder

BackgroundThis study aimed to evaluate the GIT manifestation in Autistic children and relate it to the degree of autism to demonstrate the possible connection between celiac disease and autism. An observational cross-sectional study with analytic component was carried out on 114 children with autism spectrum disorder above 3 years who visited to Phoniatric Unit, Mansoura University Hospitals and were separated into three groups according to DSM-V each of them contained 38 children, group I (children with level I ASD), group II (children with level II ASD), and group III (children with level III ASD).ResultsFifty percent of ASD children in the studied groups showed at least one GIT symptom. Constipation was the most common symptom. The existence of gastrointestinal signs was shown to have a substantial link with the severity of autism. None of the youngsters had celiac disease.ConclusionGastrointestinal issues are frequent in ASD children and may lead to ASD behavioral symptoms. It is possible that children with more severe autism are more prone to suffer from gastrointestinal issues, and the other way around. This research found no evidence to demonstrate a connection between autism spectrum disorder and celiac illness.

Celiac Disease and Autoimmune Thyroid Disease: The Two Peas in a Pod.

Celiac disease (CD) is a small intestinal inflammatory disease commonly seen in the Western population. It has been observed that patients with monoglandular and polyglandular autoimmunity have a higher prevalence of celiac disease. Hashimoto's thyroiditis (HT) and Graves' disease (GD), which mainly constitute the autoimmune thyroid diseases (AITD), characterized by lymphocytic infiltration of the thyroid parenchyma, are noted to be frequently associated with celiac disease. The fundamental mechanism of this frequent coexistence is thought to be a shared genetic background. Due to the subclinical nature of the celiac disease, the diagnosis is often missed or made coincidentally during screening. The rising prevalence of the celiac disease among AITD patients has urged researchers to investigate the link between the two. We reviewed the most recent and relevant literature on the intriguing relationship between celiac disease and thyroid autoimmunity. The objectives of this article were to study the shared genetic background, the incidence of CD in AITD, the effect of a gluten-free diet on AITD, and the need for routine screening of CD in AITD patients.

Isolated positive deamidated gliadin peptide-IgG has limited diagnostic utility in coeliac disease.

AimDeamidated gliadin peptide‐IgG (DGP‐IgG) antibody serology testing is widely utilised in screening for coeliac disease in Australia; however, it is used sparingly in Europe. The aim of this study was to assess the diagnostic value of a positive DGP‐IgG in the setting of a negative tissue transglutaminase‐IgA (tTG‐IgA) for gastrointestinal pathology among paediatric patients.MethodsWe conducted a retrospective cohort study of all children with an elevated DGP‐IgG in the setting of a negative tTG‐IgA who underwent gastroscopy over a 48‐month period (January 2015–December 2018) at a tertiary paediatric centre. They were identified utilising the electronic pathology database and demographic and clinical data were collected from electronic medical records. Patients who had previously been diagnosed with coeliac disease were on a gluten‐free diet or over the age of 18 were excluded from the study.ResultsTwenty‐six patients with an elevated DGP‐IgG in the setting of a negative tTG‐IgA underwent gastroscopy. Our study yielded a positive predictive value of 1/26 (3.9% CI 95% 0.7%, 18.9%) for the diagnosis of coeliac disease. Overall, there were 25 histopathological diagnoses including 1 diagnosis of coeliac disease among the total 26 patients who were positive DGP‐IgG and negative tTG‐IgA and underwent gastroscopy.ConclusionsOur findings suggest that an isolated positive DGP‐IgG has a very low diagnostic yield for coeliac disease in children and may be indicative of other gastrointestinal pathology.

Celiac Disease and Bariatric Surgery: A Systematic Review of Current Literature

Background: Celiac disease (CD) is a clinical entity increasingly recognized in the severe obese population and its impact on outcomes following bariatric surgery is not currently understood. We aimed to systematically review the nutritional and clinical outcomes for patients with obesity and CD following bariatric surgery. Methods: Systematic search of MEDLINE, Embase, Scopus, and Web of Science was conducted in September 2021. Study followed PRISMA guidelines. Studies evaluating adult patients with CD undergoing bariatric surgery were included. Outcomes were descriptive due to limited studies. Results: Our literature review produced 9 studies with 152 patients. The weighted mean age of included patients was 44.2 years (±9.55 years) and 98% (n = 149) were female. Patients diagnosed with CD post-operatively appear to experience substantial perioperative and nutritional complications following bariatric surgery. However, pre-operative diagnosis may allow patient optimization and current studies suggest similar bariatric surgery outcomes can be achieved in these patients when the diagnosis is known. However, this study also highlights a scarcity of evidence evaluating the rate of CD and outcomes for these patients after bariatric surgery. Conclusion: Current literature lacks quality, comparative studies investigating the short- and long-term surgical complications and nutritional outcomes of bariatric surgery within patients who have co-diagnoses of obesity and CD. Despite these limitations, our group recommends pre-operative CD screening in patients experiencing either classical GI symptoms of CD including diarrhea, steatorrhea, bloating, or undifferentiated abdominal pain.

The development and validation of a high-capacity serological assay for celiac disease

BackgroundThe aim of the present study was to develop and clinically validate a high-throughput assay for serum IgA and IgG antibodies against transglutaminase-2 (TG2) and to determine appropriate assay cut-offs for large-scale population screening for celiac disease. MethodAn automated method was developed using dual label time-resolved fluorometry on the AutoDELFIA platform. Individuals (n = 1920) from the general population were screened. Subjects with serum anti-TG2 concentrations above a preliminary cut-off (>0.3 mg*/L anti-TG2 IgA or >0.5 mg*/L anti-TG2 IgG) were offered endoscopic examination and biopsy. A diagnosis of celiac disease was given if villous atrophy (Marsh grade 3) was found. ResultsThe assay had a limit of quantification of 0.25 mg*/L (anti-TG2 IgA) and 0.60 mg*/L (anti-TG2 IgG) with imprecision (CV) < 16% and <18% respectively. A total of 66 individuals were above the preliminary cut-off, and 56 underwent endoscopy. Of these, 26 were diagnosed with celiac disease. Sixty-eight percent of subjects with anti-TG2 IgA ≥ 0.7 mg*/L or anti-TG2 IgG ≥ 1.0 mg*/L had biopsy-proven celiac disease, and utilization of these higher cut-offs identified 96% of biopsy-positive patients. At the time of endoscopy, all individuals with anti-TG2 IgA > 2.0 mg*/L had celiac disease, and this cut-off identified 88% of newly diagnosed celiac patients. Eight percent (2/26) of the newly diagnosed patients had primarily anti-TG2 IgG. ConclusionsIn this study we developed and clinically validated a robust and automated assay suitable for celiac disease screening in the general population.

Prevalence of Celiac Disease in Adult Patients with Iron Deficiency Anemia

Background and Aim: Celiac disease is a gastrointestinal condition that is chronic and mediated by an immunological reaction to gluten present in different grains such as wheat, barley, and rye. Studies document that the incidence of celiac disease within the Pakistani population to be 29.3% and is highly prevalent among the younger age groups. Iron deficiency anemia is a major cause of anemia around the world, especially in developing countries such as Pakistan. Anemia has been acknowledged to be one of the major manifestations of celiac disease worldwide. This study will aim to assess the incidence and burden of celiac disease among the known anemic adult population of due to iron deficiency in tertiary care hospitals of Khyber Pakhtoonkhaw. Methodology: A cross-section study was conducted in the department of Gastroenterology Bacha Khan Medical Complex, Swabi and Northwest General Hospital &amp; Research Centre Hayatabad, Peshawar during the period of six months from May 2021 to October 2021. Participants were recruited after assessment of criteria. All recruited participants were anemic and underwent extensive serological assessment for screening of celiac disease. For confirmation of celiac disease duodenal biopsies were performed at five different levels. Results: 5.4% of the participants (n= 108) were found to have positive results for screening of IgA tTG. 38% of these participants (n= 41) showed IgA tTG ranging between 20 – 79 who were found negative for IgA EMA. These participants were kept on a gluten-free diet for the following 6 months and were scheduled on a recall assessment after 6 months and then 1 year of diet. On follow up duodenal biopsies were performed for these participants and the outcomes were classified as Marsh 0. These participants comprising 38% of IgA tTG screening were discarded from the possible suspect of celiac disease.The remaining 62% (n= 67) population of positive IgA tTG screening test, comprising 3.35% of the entire recruited population had values for IgA tTG of greater than 100 and showed positive results in serology reports of IgA EMA. All 67 participants who tested positive underwent duodenal endoscopy on five sites for a definite diagnosis of celiac disease and were found to be celiac disease positive Conclusion: The study concludes that the prevalence of the celiac disease among the anemic population is high, and anemia can be considered an extra gastric manifestation of celiac disease. Majority of identified participants were female and shows a predilection for female susceptibility. Keywords: Iron deficiency, Celiac disease, Prevalence, Correlation.

Emerging Biomarkers for Screening and Management of Celiac Disease.

Celiac disease (CeD) is a chronic, immune-mediated enteropathy that is precipitated by dietary gluten in genetically predisposed individuals expressing HLA-DQ2 and/or HLA-DQ8. In the current clinical practice, there are many serologic studies to aid in the diagnosis of CeD which include autoantibodies like IgA antitissue transglutaminase, antiendomysium, and antideamidated forms of gliadin peptide antibodies. Small intestinal biopsy has long been considered an essential step for the diagnosis of CeD. However, in the recent era, researchers have explored the possibility of CeD screening and diagnosis without endoscopy or biopsy. The newer emerging biomarkers of CeD appear promising in diagnostic evaluation and subsequent monitoring of disease. In this review of literature, we have explored the emerging biomarker-based diagnostic evaluation and monitoring of CeD.

Serological screening of celiac disease in children and adolescents with juvenile idiopathic arthritis

Background Patients with juvenile idiopathic arthritis (JIA) seem to be at higher risk of developing immune-mediated diseases like celiac disease (CD) than general population. Aim The aim of this study was to detect the prevalence of CD among children and adolescents with JIA. Patients and methods We carried out a cross-sectional study that included 42 JIA patients under the age of 16 years. In addition to demographic, clinical, and laboratory data, anti-tissue transglutaminase immunoglobulin A (anti-TTG IgA) antibodies were measured using a novel chemiluminescent immunoassay. Results Only one (2.4%) patient had positive anti-TTG IgA. There was no significant correlation between anti-TTG IgA and terms of growth parameters, JIA subtype, or medications. Conclusion JIA patients seem to be at higher risk to develop CD. Being mostly asymptomatic, they should be candidates for periodic screening. Methodologically standardized larger studies are recommended to reach a cost-effective protocol for monitoring JIA patients regarding the development of CD, adding to early diagnosis and control of the disease.

Early vs late histological confirmation of coeliac disease in children with new-onset type 1 diabetes

AimScreening for coeliac disease in asymptomatic children with new-onset type 1 diabetes is controversial. The aim of this study was to analyse whether the confirmation of coeliac disease in children with new-onset type 1 diabetes and positive screening results can be postponed.MethodsThis was a multicentre population-based cohort study based on the German/Austrian/Swiss/Luxembourgian Prospective Diabetes Follow-up Registry (Diabetes Patienten Verlaufsdokumentation [DPV]). Participants aged ≤18 years diagnosed with type 1 diabetes between 1995 and June 2021 and with elevated IgA tissue transglutaminase antibodies (anti-tTGA) at diabetes onset on screening for coeliac disease were included. We compared outcomes of participants with a diabetes duration of more than 1 year between those in whom coeliac disease was confirmed histologically within the first 6 months and those in whom coeliac disease was confirmed between 6 and 36 months after diabetes diagnosis.ResultsOf 92,278 children and adolescents with a diagnosis of type 1 diabetes, 26,952 (29.2%) had documented anti-tTGA data at diabetes onset. Of these, 2340 (8.7%) had an elevated anti-tTGA level. Individuals who screened positive were younger (median age 9.0 vs 9.8 years, p<0.001) and more often female (53.1% vs 44.4%, p<0.001). A total of 533 participants (22.8% of those who screened positive) had a documented biopsy, of whom 444 had documented histological confirmation of coeliac disease. Of 411 participants with biopsy-proven coeliac disease within the first 36 months of diabetes and follow-up data, histological confirmation was performed in 264 (64.2%) within the first 6 months and in 147 (35.8%) between 6 and 36 months after diabetes onset. At follow-up (median diabetes duration 5.3 years and 5.1 years, respectively), estimated median HbA1c levels (62.8 mmol/mol vs 62.2 mmol/mol [7.9% vs 7.8%]), cardiovascular risk markers (lipids, rate of microalbuminuria, blood pressure), rates of acute diabetes complications (diabetic ketoacidosis, severe hypoglycaemia) and the proportions of participants reaching anti-tTGA levels within the normal range did not differ between groups. Participants with delayed histological confirmation of coeliac disease showed no negative effects on growth or weight gain during the observation period.ConclusionsOur study suggests that the histological confirmation of coeliac disease in asymptomatic individuals with new-onset type 1 diabetes could be postponed.Graphical abstract

Prediction Models for Celiac Disease Development in Children From High-Risk Families: Data From the PreventCD Cohort

Screening for celiac disease (CD) is recommended in children with affected first-degree relatives (FDR). However, the frequency of screening and at what age remain unknown. The aims of this study were to detect variables influencing the risk of CD development and develop and validate clinical prediction models to provide individualized screening advice. We analyzed prospective data from the 10 years of follow-up of the PreventCD-birth cohort involving 944 genetically predisposed children with CD-FDR. Variables significantly influencing the CD risk were combined to determine a risk score. Landmark analyses were performed at different ages. Prediction models were created using multivariable Cox proportional hazards regression analyses, backward elimination, and Harrell's c-index for discrimination. Validation was done using data from the independent NeoCel cohort. In March 2019, the median follow-up was 8.3 years (22 days-12.0 years); 135/944 children developed CD (mean age, 4.3 years [range, 1.1-11.4]). CD developed significantly more often in girls (P= .005) and in Human Leukocyte Antigen (HLA)-DQ2 homozygous individuals (8-year cumulative incidence rate of 35.4% vs maximum of the other HLA-risk groups 18.2% [P < .001]). The effect of homozygosity DR3-DQ2/DR7-DQ2 on CD development was only present in girls (interaction P= .04). The prediction models showed good fit in the validation cohort (Cox regression 0.81 [0.54]). To calculate a personalized risk of CD development and provide screening advice, we designed the Prediction application https://hputter.shinyapps.io/preventcd/. Children with CD-FDR develop CD early in life, and their risk depends on gender, age and HLA-DQ, which are all factors that are important for sound screening advice. These children should be screened early in life, including HLA-DQ2/8-typing, and if genetically predisposed to CD, they should get further personalized screening advice using our Prediction application. ISRCTN74582487 (https://www.isrctn.com/search?q=ISRCTN74582487).

HLA DQ2/DQ8 haplotypes and anti-transglutaminase antibodies as celiac disease markers in a pediatric population with type 1 diabetes mellitus.

Evaluate the celiac disease (CD) markers, within the scope of its screening, in a pediatric population with diagnosis of type 1 diabetes (T1D) at Hospital de Braga (HB) and determine the prevalence of CD in the sample. Reflect on CD screening algorithm applied in this pediatric population. Retrospective observational study with 94 patients diagnosed with T1D at age 10 years or younger, followed up at the HB Outpatient Diabetology Consultation, including those referred from other hospitals. Record of clinical information, IgA anti-transglutaminase and anti-endomysium and HLA DQ2/DQ8 haplotypes. We obtained positive serological test for CD in 4 patients. This test had 100% sensitivity and specificity. The prevalence of CD was 4.3% (n = 4). Positive HLA screening in 84.6% of patients, with both sensitivity and negative predictive value of 100% and specificity of 16.67%. Diagnosis of CD was made on average 3.40 ± 3.32 years after the diagnosis of TD1. All cases of CD registered non-gastrointestinal manifestations, none had gastrointestinal symptoms. This study proved that there is a higher prevalence of CD in pediatric population with TD1, when compared to general population, and clarified the importance of CD screening. Furthermore, it was observed that serological screening for CD antibodies is an excellent screening test and HLA typing, although not the most suitable first line test, can be useful in excluding the possibility of patients with T1D developing CD.

Combination of HLA-DQ2/-DQ8 Haplotypes and a Single MSH5 Gene Variant in a Polish Population of Patients with Type 1 Diabetes as a First Line Screening for Celiac Disease?

Patients with type 1 diabetes (T1D) are at increased risk for developing celiac disease (CD). The aim of the study was to assess the usefulness of celiac-specific human leukocyte antigen (HLA) haplotype and the rs3130484 variant of MSH5 gene, a previously described non-HLA variant associated with CD in the Polish population as a first-line screening for CD in T1D pediatric patients. Serological CD screening performed in the T1D group (n = 248) and healthy controls (n = 551) allowed for CD recognition in 20 patients (8.1%) with T1D (T1D + CD group). HLA-DQ2, HLA-DQ8 and the rs3130484 variant were genotyped with TaqMan SNP Genotyping Assays. The T1D + CD group presented a higher, but not statistically significant, frequency of HLA-DQ2 in comparison with T1D subjects. Combining the rs3130484 with HLA-DQ2/HLA-DQ8 typing significantly increased the sensitivity of HLA testing from 32.7% to 68.7%, and the accuracy of estimating CD prediction from 51.7% to 86.4% but decreased the specificity from 100% to 78.2%. The receiver operating characteristic curve analysis confirmed the best discrimination for the combination of both genetic tests with an area under curve reaching 0.735 (95% CI: 0.700–0.7690) in comparison with 0.664 (95% CI: 0.632–0.696) for HLA typing alone. Results show the low utility of HLA-DQ2/HLA-DQ8 typing for CD screening in T1D pediatric patients. Combination of the rs3130484 variant of the MSH5 gene and HLA testing increases both the sensitivity and the predictive value of the test accuracy, but still, the obtained values are not satisfactory for recommending such testing as the first-line screening for CD in T1D patients.

Anti-tissue transglutaminase (tTG) screening using relative light units to identify IgA deficiency

IgA deficiency is more common in patients with coeliac disease (CD). Total IgA levels are often recommended as part of first line coeliac testing along with anti-tissue transglutaminase (tTG) IgA, to identify these patients and reduce falsely negative results. This study aimed to identify patients with complete IgA deficiency by determining a cut-off threshold on chemiluminescent tTG IgA testing. A chemiluminescent assay QUANTA Flash h-tTG was reviewed using the BIO-FLASH automated platform. tTG relative light units (RLU) were analysed in relation to total IgA levels. Correlation analysis was performed and distributions of tTG RLU were compared between the IgA deficient and IgA detectable groups, and ROC analysis was performed to identify a suitable threshold. A total of 203 samples were reviewed in our initial cohort. There was a strong correlation between IgA and tTG RLU levels (Pearson correlation coefficient 0.495, p<0.001). There was a statistically significant difference of 170.57 RLU between the means of the IgA deficient and IgA detectable group (p<0.001, 156.50-184.64). A receiver operating characteristic (ROC) curve was generated with area under the curve of 0.997. A cut-off of less than 300 tTG RLU for identification of IgA deficiency was chosen, which had a sensitivity and specificity of 100% and 98.9%, respectively. A prospective validation cohort was conducted which confirmed the initial results. Our study has validated an algorithm to identify complete IgA deficiency by implementing a threshold of 300 RLU during tTG IgA testing by chemiluminescent immunoassay. This approach resulted in a sensitivity of 100% to detect patients with complete IgA deficiency. Widespread uptake would result in improved workflow, workload and turnaround time, and reduce the need for unnecessary blanket testing of total IgA in the screening for coeliac disease.

IDF21-0185 Prevalence of autoimmune diseases in young patients with type 1 diabetes

Background: Autoimmunity and viral infections are the main etiopathological factors implicated in the pathogenesis of T1DM on the background of genetic predisposition. Type 1 diabetes mellitus (T1DM) is associated with various autoimmune disorders like celiac disease, thyroid disorder, adrenal failure, etc. However, how common is this association in Indian children is not clearly known. Aim: This cross-sectional study was planned to investigate the prevalence of autoimmune disorders like autoimmune thyroid disorders, celiac disease, and other autoimmune disorders in T1DM. Method: In this cross-sectional study, patients requiring insulin and ketosis-prone diabetic and with history of diabetic ketoacidosis/undetectable fasting C-peptide levels were included. Beside demographic and clinical data, detailed biochemistry evaluations were performed. Celiac disease was diagnosed as per the ESPGHAN diagnostic criteria. ACTH stimulation test was done to confirm the adrenal insufficiency in patients with basal serum cortisol <5 μg/dL. Thyroid function test (TSH) and anti-TPO antibody were assessed in all patients. Screening for other autoimmune disorders was done only when clinically indicated or symptoms or family history was suggestive of presence of such disorder. Results: Among 200 patients enrolled, 65% were males and mean age was 12.37 ± 3.34 years. Mean age at diagnosis of T1DM was 10.1 ± 3.58 years and duration of diabetes was 3.52 ± 3.21 years. The prevalence of antibodies positive against autoimmune diseases was anti-tTG IgA (21%), anti-TPO (34%), anti-CCP ab (1.5%), and ANA (0.8%). Significantly higher proportion of females had raised anti-TPO antibodies than males (48.1% vs. 26.4%, P = 0.005). Celiac disease was most common association (25.4%) followed by hypothyroidism (13.8%) and Grave's disease (3.2%). Significantly higher proportion of females had hypothyroidism than males (26.1% vs. 8.6%, respectively, P = 0.006). Prevalence of raised anti-tTG and anti-TPO did not differ significantly by the age (P = 0.841 and P = 0.067) or duration of T1DM (P = 0.493 and P = 0.399). Discussion: In this part of country, celiac disease, hypothyroidism, and Graves's disease are common associations in children with T1DM. This study also emphasizes the importance of total IgA estimation and duodenal biopsy in IgA anti-tTG-negative patients having strong suspicion of celiac disease on the basis of history. This study reinforces a call to improve the quality of healthcare services, including implementation of universal screening for thyroid dysfunction and celiac disease in children with T1DM.

Celiac disease screening at a pediatric outpatient clinic: a feasibility study

Objectives Celiac disease (CD) is a common yet largely underdiagnosed disease. This study aimed to test the feasibility of incorporating a non-targeted CD screening in a pediatric outpatient setting and evaluate its short-term impact on children with serological evidence of disease. Methods Over five months, 500 children (aged 2–17 years) attending a general pediatric outpatient clinic in Gothenburg, Sweden, were enrolled and surveyed for current symptoms, quality of life, and background characteristics; 481 children were screened for tissue-transglutaminase antibodies (tTGA); repeated tTGA-positivity was defined as CD autoimmunity (CDA). Children with CDA were investigated for CD and for one year monitored for changes in symptoms, and quality of life. Results Eleven of 481 (2.3%) screened children had CDA. Children with CDA were younger (median 3.8 years) than those without CDA (8.8 years). No other major between-group differences were reported in background characteristics, symptoms, or quality of life. The screening was well-accepted by the families/participants. During 1-year follow-up, 8 of 11 children with CDA were diagnosed with CD. Children with screening-detected CD reported no significant changes in symptoms and quality of life and the dietary adherence rate was good. Conclusions Non-targeted screening for CD was feasible in a general pediatric outpatient setting. While hampered by small sample size, our results are in line with previous screening studies indicating that symptoms do not differentiate CDA from non-CDA children. Also, among an overall minimal-symptomatic group of children, diagnosing CD and installation of treatment did not significantly change their well-being during 1-year follow-up.