Positive Endomysial Antibodies Research Articles

Trends in the prevalence rates and predictive factors of coeliac disease: A long-term nationwide follow-up study.

The prevalence of coeliac disease doubled in Finland from 1980 to 2000. To investigate whether this increase is continuing and if there are specific patient-related factors predicting the development of coeliac disease at a population level. We elicited comprehensive health data in the nationwide Health 2000 and Health 2011 surveys. Serum samples were taken for the measurement of tissue transglutaminase antibodies (TGA); subjects who were seropositive were tested for endomysial antibodies (EmA). Coeliac disease was defined either as a reported diagnosis or as positive TGA and EmA. The surveys comprised, respectively, 6379 and 4056 individuals, forming representative samples for 2,946,057 and 2,079,438 Finnish adults. Altogether 3254 individuals participating in both surveys comprised a prospective follow-up cohort. Prevalence of coeliac disease was 2.12% in 2000 and 2.40% in 2011 (p = 0.156). In the prospective cohort, 16 out of the 3254 (0.49%) subjects developed coeliac disease during follow-up from 2000 to 2011, with an annual incidence rate of 45 per 100,000 persons. Positive TGA without EmA (OR: 133, 95% CI: 30.3-584), TGA values in the upper normal range (51.1, 16.0-163), and after adjusting for TGA, previous autoimmune co-morbidity (8.39, 4.98-35.9) in 2000 increased the likelihood of subsequent coeliac disease. The nationwide prevalence of coeliac disease kept on rising from 2.12% in 2000 to 2.40% in 2011 in Finland. Positive TGA without EmA, TGA titres in the upper normal range and a pre-existing autoimmune disease predisposed to coeliac disease during the 10-year follow-up.

Diagnosing Coeliac Disease During Mass-Screening of General Paediatric Population: Is Biopsy Avoidable?

Studies evaluating the correlation between tissue transglutaminase immunoglobulin antibody (TGA-IgA) levels and the degree of enteropathy in screening-detected coeliac disease (CD) patients from the general childhood population are scarce. The objectives of our study were to evaluate the correlation between the TGA-IgA titre and the degree of enteropathy and to evaluate whether the no-biopsy approach to diagnose CD in symptomatic patients proposed by the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition could be extended to asymptomatic CD patients diagnosed during mass screening studies. The present study is a sub-study of a cross-sectional mass screening study, "Exploring the Iceberg of Coeliacs in Saudi Arabia", conducted among school-aged children (6-15 years) in 2014-2015. The 93 biopsy-confirmed CD patients constituted the study cohort of the present study (mean age 11.4 ± 2.6 years; 24 males). TGA-IgA titres and endomysial antibodies (EMA) at the time of biopsy and grade of enteropathy were assessed, and human leukocyte antigen DQ 2.2/2.5/8 genotyping was performed. Thirty-four patients had TGA-IgA titres >10× upper limit of normal (ULN; 36%); all had villous atrophy with positive EMA and DQ 2.2/2.5/8. The sensitivity and specificity of a TGA-IgA titre >10× ULN in correctly diagnosing CD was 100%. There was a significant positive correlation between the anti-TGA-IgA titre and the severity of enteropathy (P < 0.001). There was no significant difference in the TGA-IgA titre between the asymptomatic and symptomatic CD patients. Our results provide evidence that a TGA-IgA titre >10× ULN correlates with villous atrophy in CD patients detected by mass screening.

The impact of celiac disease and duration of gluten free diet on anterior and posterior ocular structures: Ocular imaging based study.

To evaluate the eyes of adult celiac disease (CD) patients and investigate the association between these ocular parameters with celiac specific antibodies and duration of gluten free diet (GFD). This cross-sectional study included 72 eyes of 36 CD patients (18-51 years of age) and 70 eyes of 35 age- and sex-matched healthy controls. In addition to a complete ophthalmologic examination, all patients were scanned by a Scheimpflug camera, specular microscopy and spectral domain optical coherence tomography. Endothelial cell density (ECD), anterior chamber angle (ACA) degrees, anterior chamber depth (ACD), anterior chamber volume (ACV) and central macular thickness (CMT) values were lower in CD patients as compared with control group (p values = 0.038, 0.024, 0.002, 0.038 and 0.046 respectively). ECD and CMT were lower in celiac patients whom endomysial antibodies (EMA) IgA were positive (p = 0.001, p = 0.042 respectively). Tissue transglutaminase IgA antibody (anti tTG IgA) was weakly positively correlated (p > 0.05) with ACD, and positively (r = 0.319; p < 0.05) correlated with ACV. As the duration of compliance to the diet increased in the celiac group the mean and inferior retinal nerve fiber layer (RNFL) thickness decreased (p = 0.035, p = 0.008 respectively). Mean, inferior and temporal RNFL thicknesses were lower in celiac patients whose duration of GFD was longer than 5 years (p < 0.05). Decreases in ECD, ACA degree, ACD, ACV and CMT can occur in CD patients. In adult celiac patients; ECD, CMT might be effected in the presence of positive EMA, and ACD, ACV might be effected in the presence of higher anti tTG IgA titer. Adult celiac patients who had longer duration of GFD may have thinner RNFL. RNFL may be thinner in celiac patients who comply with GFD for more than 5 years.

Do gastroenterologists have medical inertia towards coeliac disease? A UK multicentre secondary care study

ObjectiveThis study aimed to assess if there is secondary care medical inertia towards coeliac disease (CD).DesignGroup (1): Time from primary care presentation to diagnostic endoscopy was quantified in 151 adult...

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

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

Role of serological tests in the diagnosis of coeliac disease in children in New Zealand.

To circumvent the need for an endoscopic biopsy to establish the diagnosis of coeliac disease (CD), the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) introduced a non-biopsy pathway for selected children in 2012. This pathway was recently updated to utilise anti-tissue transglutaminase IgA (anti-TTG IgA), 10× upper limit of normal (ULN) and positive endomysial antibodies (EMA). This study focused on the retrospective application of these guidelines in children from two regions of New Zealand. Children aged <18 years who had anti-TTG IgA measured and underwent oesophagogastroduodenoscopy over a 30-month period were identified retrospectively. Medical records were reviewed to determine whether patients subsequently had biopsy-proven CD (Marsh ≥2). One hundred and thirty-six children, with a mean age (±standard deviation) of 9.9 ± 4.2 years, fulfilled the study criteria and 101 (74%) of these children had positive anti-TTG IgA. Eighty-two of 136 (60%) children had biopsy-proven CD. Positive anti-TTG IgA and EMA were highly sensitive in diagnosing CD, 96.3 and 98.6%, respectively. Anti-TTG-IgA ≥10× ULN alone, and combined anti-TTG IgA ≥10× ULN with positive EMA, both provided positive predictive values of 100% in diagnosing CD. Nineteen of 103 (18%) children could have been diagnosed with CD based on the ESPGHAN non-biopsy criteria. A proportion of New Zealand children with CD can potentially be diagnosed using the latest ESPGHAN non-biopsy criteria. However, prospective studies are required to validate this conclusion.

ESPGHAN 'biopsy-sparing' guidelines for celiac disease in children with low antitransglutaminase during COVID-19.

Recent guidelines for celiac disease have allowed a biopsy-free approach in endomysial antibodies (EMAs) positive children with high antitransglutaminase (TGA-IgA) titer [>10 time upper limit of normal (ULN)]. Esophagogastroduodenoscopy is still necessary for diagnosis in children with lower title. Because elective pediatric endoscopy has been substantially shouted down during coronavirus disease (COVID-19) pandemic, many children remained undiagnosed - and therefore untreated - for a long time. We aimed to analyze the feasibility and accuracy of a biopsy-free approach in suspected celiac disease children with TGA-IgA values <10 ULN to facilitate the diagnostic process by avoiding endoscopy. In this study cohort, we retrospectively analyzed all biopsy-confirmed diagnosis of celiac disease in our center (between 2014 and 2019). The positive predictive value (PPV) of TGA-IgA titers between 5 and 10 ULN and positive EMA in diagnosing celiac disease were determined. Mucosal atrophy and resolution of symptoms after gluten-free diet (GFD) were considered to confirm initial diagnosis. Of 430 celiac disease patients (F: 274; mean age 7.54 years) diagnosed by endoscopy, 84 (F: 46; mean age 8 years) with TGA-IgA between 5 and 10 ULN and positive EMA were identified. The PPV of TGA-IgA between 5 and 10 ULN and positive EMA was 0.93 (95% confidence interval 0.90-0.96). All these children had a symptom resolution and antibodies normalization after GFD. During the COVID-19 outbreak, a temporarily reduction of the TGA-IgA threshold for biopsy-sparing approach seems feasible in EMA positive children with TGA-IgA between 5 and 10 ULN.

Assessment of European Society of Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) guidelines in an Australian paediatric population

Coeliac disease (CD) diagnosis is based on clinical assessment, detection of specific autoantibodies and histological examination of small intestinal biopsies. The European Society of Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) guidelines have recently been updated and recommend CD may be diagnosed without a biopsy or HLA typing in symptomatic patients with high titre IgA tissue transglutaminase antibodies (aTTG) and positive endomysial antibodies (EMA). However, the need for EMA in patients with high level aTTG has been questioned. We aimed to determine the diagnostic benefit of HLA typing, EMA and IgG antibodies to deamidated gliadin (DGP) in children with high level aTTG. We prospectively evaluated children presenting for assessment of possible CD. All patients underwent small bowel biopsy, serological testing and HLA typing. Results were analysed and correlated with histopathological diagnosis. A total of 209 children were assessed; 61.5% were found to have CD and 29% could have avoided biopsy as per 2020 ESPGHAN guidelines. Titres of aTTG ≥60 U/mL or DGP ≥28 U/mL gave 100% specificity and 100% positive predictive value (PPV) for CD. HLA typing and EMA did not improve the PPV of patients with aTTG ≥60 U/mL, but addition of DGP ≥28 U/mL improved diagnostic sensitivity whilst retaining 100% specificity. Addition of HLA and EMA testing in patients with high titre aTTG antibodies does not improve diagnostic performance and may possibly be omitted from the serological workup in these patients. Our data support combining aTTG and DGP testing and optimising cut-offs to maximise specificity as an alternative biopsy-free diagnostic approach.

Screening of celiac disease in children and adolescents with type 1 diabetes mellitus

Background and aim: Celiac disease is the most frequent autoimmune disease in Type 1 diabetes mellitus. We aimed to determine the celiac disease prevalence in patients with type 1 diabetes mellitus, additionally to evaluate the clinical, serological and molecular characteristics of type 1 diabetes mellitus and celiac disease which have a common genetic predisposition. Material and methods: A total number of 76 type 1 diabetes mellitus patients aged between 1-18 years, were evaluated retrospectively. Serologic screening for celiac disease was performed via anti-tissue transglutaminase and anti-endomysial antibodies. Presence of human leukocyte antigens (HLA) (DQ2 and DQ8) documented as well. Patients with positive tissue transglutaminase and endomysial antibodies underwent endoscopic biopsy. Histopathological analysis were performed according to the modified Marsh classification. Patients' demographic characteristics, anthropometric measurements, physical examination, laboratory findings, age at type 1 diabetes mellitus and celiac disease onset, and celiac disease prevalence were evaluated. In addition all findings were compared between type 1 diabetes mellitus patients and newly diagnosed celiac disease patients. Results: Serum tissue transglutaminase was positive in 14,5% (n=11) of all patients and serum endomysial antibodies was positive in 13,2% (n=10). The overall prevalence of celiac disease in type 1 diabetes mellitus was confirmed as 10.5% (n=8) by histopathological examination in present study. Of the celiac disease patients 37.5% were asymptomatic. In addition, 6 were anti-tissue transglutaminase and 7 were endomysial antibodies positive. Moreover, 60.3% (n=41) were HLADQ2 and 58.8% (n=40) were HLA-DQ8 positive. Selective IgA deficiency was described in 3 cases. In one of them HLA-DQ2/HLA-DQ8 was found positive and celiac disease diagnosis was confirmed by biopsy. HLA-DQ8 ratio was found significantly higher in patients with celiac disease than the type 1 diabetes mellitus patients. In addition, HLA-DQ2/DQ8 positivity was observed in 62.5% (n=5) of celiac disease patients. Conclusion: Our findings have demonstrated the increasing prevalence of celiac disease in children with type 1 diabetes mellitus. Particularly the higher risk of asymptomatic celiac disease in type 1 diabetes mellitus patients, revealed the diagnostic value of serological screening. Furthermore, increased HLA-DQ2 and HLA-DQ8 positivity, which are more prominent in case of selective IgA deficiency, clearly demonstrates the requirement of routine total IgA and HLA analysis in serological screening.

Iron deficiency workup reveals high incidence of autoimmune gastritis with parietal cell antibody as reliable screening test

Iron deficiency (ID) workup is a common challenge for gastrointestinal endoscopy. In premenopausal women current guidelines recommend serologic evaluation of coeliac disease only. Here we systematically tested serologic screening for autoimmune gastritis (AIG) in a large cohort of patients with ID. This is a retrospective analysis of patients who attended an out-patient clinic specialized for ID. Patients with ferritin <50 µg/L or transferrin saturation <15% were included. Laboratory workup included endomysial antibodies and parietal-cell antibodies (PCA). Upper gastrointestinal endoscopy with pH-measurement of gastric juice and histology was performed to confirm positive serologic results. Three hundred seventy-three patients with ID were included, about half of whom were anemic. Patients were predominately female with a median age of 40 (confidence interval 11). Positive endomysial antibodies were found in 4 (1%) patients, elevated levels of PCA (>20 U/mL) were found in 69 (18.5%) patients, PCA >100 U/mL in 23 (6.2%). Twenty-six were followed up by gastroscopy; in 12 of 26 patients the diagnosis of AIG was confirmed by histology with 2 additional patients diagnosed as early and/or questionable AIG. A sensitivity of 93% and a specificity of 98% were estimated for a PCA cut-off of 100 U/mL. In 20 patients gastric pH was measured. Achlorhydria was found in 7 patients all diagnosed with AIG. In this ID cohort AIG is by far more common than coeliac disease. PCA above 100 U/mL are a sensitive and specific cut-off for workup of patients with ID prior to endoscopy. Serologic suspicion of AIG helps preselection of patients for endoscopic workup for ID.

Gluten neuropathy: prevalence of neuropathic pain and the role of gluten-free diet.

Peripheral neuropathy is a common extraintestinal manifestation of gluten sensitivity (gluten neuropathy). We aimed to establish the prevalence of neuropathic pain in patients with otherwise idiopathic PN and gluten sensitivity (positive antigliadin, endomysial, and/or transglutaminase antibodies, with or without enteropathy) and to describe any contributory factors. All consecutive patients with gluten neuropathy (GN) attending a specialist gluten/neurology clinic were invited to participate. Pain was assessed via the DN4 questionnaire and the visual analog scale. Overall Neuropathy Limitations Scale was used to assess the severity of neuropathy. The Mental Health Index (MHI-5) was used to measure participants' general mental health status. In total, 60 patients (76.7% males, mean age 69.9 ± 10.1years) with GN were recruited. Neuropathic pain was present in 33 patients (55.0%). Comparison between groups of painful and not painful GN did not show significant differences regarding age, gender, neuropathy severity and neuropathy type. Patients with painless GN were more likely to be on a strict gluten-free diet (55.6 versus 21.2%, p = 0.006). Patients with painful GN presented with significantly worse MHI-5 score (75.9 ± 13.8 versus 87.4 ± 8.1, p < 0.001). Multivariate analysis showed that, after adjusting for age, gender and MHI-5, strict gluten-free diet was associated with lowering the odds of peripheral neuropathic pain by 88.7% (95% CI 47.2-97.6%, p = 0.006). Neuropathic pain is very prevalent in GN and is associated with poorer mental health status. Strict gluten-free diet might be protective as it is associated with a significant reduction of the odds of peripheral neuropathic pain associated to GN.

Systematic review with meta-analysis: the prevalence of coeliac disease in patients with osteoporosis.

Earlier studies have produced highly varying risk estimates for the prevalence of coeliac disease (CD) in osteoporosis. To investigate the prevalence of CD among individuals with osteoporosis. We conducted a systematic review of articles published in PubMed, Medline or EMBASE through May 2017 to identify studies looking at prevalence of CD in patients with osteoporosis. Search terms included "coeliac disease" combined with "fractures", "bone disease", "bone density", "densitometry", "osteoporos*", "osteomal*", "osteodys" or "dexa" or "dxa" or "skelet". Non-English papers with English-language abstracts were included. We used fixed-effects inverse variance-weighted models, and tested heterogeneity through subgroup analysis as well as through meta-regression. We identified eight relevant studies, comprising data from 3188 individuals with osteoporosis. Of these, 59 individuals (1.9%) had CD. A weighted pooled analysis demonstrated biopsy-confirmed CD in 1.6% (95% CI=1.1%-2.0%) of individuals with osteoporosis. The heterogeneity was moderate (I2 =40.1%), and influenced by the underlying CD prevalence in the general population. After adding four studies (n=814) with CD defined as positive tissue transglutaminase or endomysial antibodies, the pooled prevalence was comparable (1.6%; 95% CI=1.2%-2.0%). About 1 in 62 individuals with osteoporosis, or 1.6%, have biopsy-verified CD. This prevalence is comparable to that in the general population. These findings argue against routinely screening patients with osteoporosis for CD, which is contrary to current guideline recommendations. Additional studies are needed to determine the true utility of such screening programs.

A subset of patients with pemphigoid (herpes) gestationis has serological evidence of celiac disease.

Pemphigoid (herpes) gestationis (PG) is an uncommon, self-limited disease with other autoimmune associations; however, celiac disease (CD) is not recognized as one. From 71 patients' sera submitted for herpes gestationis factor (HGF) testing over a 5-year period, 12 were consistent with PG demonstrating HGF and increased IgG BP180 antibody levels; these sera were tested for IgA and IgG endomysial antibodies (EMA), epithelial basement membrane zone and cell surface antibodies by indirect immunofluorescence, and for IgA and IgG tissue transglutaminase (transglutaminase 2 or TG2) antibodies, IgA epidermal transglutaminase (transglutaminase 3 or TG3) antibodies, IgG BP230, and IgG desmoglein 1 and desmoglein 3 antibodies by enzyme-linked immunosorbent assays (ELISAs). Three of 12 patients' sera with PG (25%) had CD antibodies with positive IgA EMA and increased IgA TG2 antibody levels; two of these had positive IgG EMA, and one other had an increased IgA TG3 antibody level. A subset of patients with serological findings of PG also has serological evidence of CD, which may have implications in the etiopathogenesis of PG and which reveals important information about the mother's, and possibly her infant's, health.

Detecting endomysial and tissue transglutaminase antibodies in patients with giardiasis

Celiac disease is a genetic disease diagnosed to be associated with chronic intestinal inflammation. Endomysial and tissue transglutaminase antibodies are the best serum markers for celiac disease (CD) diagnosis. This research aimed to determine the levels of endomysial and tissue transglutaminase antibodies in patients with giardiasis. Forty cases of giardiasis were selected among the referees to Milad Hospital in Tehran, as well as a children’s hospital and some health centers in Karaj. Euro-immune IgA immunofluorescence and ELISA were utilized to measure their titers of endomysial and tissue transglutaminase antibodies, respectively. Twenty random serum samples of negative Giardia and 16 serum samples of positive anti-(tissue transglutaminase) tTG antibodies were evaluated by using ELISA and endomysium antibody through immunofluorescence techniques. Among the 40 cases of giardiasis, 16 positive endomysial and transglutaminase antibodies (40%) were detected. Sixteen positive samples of endomysial antibody (EMA) were also positive for anti-tTG, and 20 random negative samples were negative for EMA and anti-tTG. The chi-square test revealed a significant association between antibodies and giardiasis (P = 0.001). Atrophy of the intestinal villi can arise after giardia infection by mimicking the behavioral patterns of anti-EMA and anti-tTG antibodies. Due to low specificity, anti-gliadin antibody test is not helpful in detecting CD in patients with giardiasis. In the present study on anti-EMA and anti-tTG in patients with giardiasis, these antibodies were positive in giardiasis. Thus, the best and most reliable way to diagnose CD and treat giardiasis is intestinal biopsy as the gold standard method.

Machine Learning in Detection of Undiagnosed Celiac Disease

Machine Learning in Detection of Undiagnosed Celiac Disease

Validation of celiac disease diagnoses recorded in the Danish National Patient Register using duodenal biopsies, celiac disease-specific antibodies, and human leukocyte-antigen genotypes.

PurposeThe purpose of this study was to validate the celiac disease diagnoses recorded in the Danish National Patient Register. To validate the diagnoses, we used information on duodenal biopsies from a national register of pathology reports (the Patobank) and information on celiac disease-specific antibodies and human leukocyte antigen (HLA) genotypes obtained from patient medical records.Patients and methodsWe included all the children who were born from 1995 to 2012 and who were registered as having celiac disease in the Danish National Patient Register. We reviewed all the pathology reports on duodenal biopsies in the Patobank and the information in the medical records on celiac disease-specific antibodies (ie, anti-tissue transglutaminase 2 IgA and IgG, endomysial antibodies IgA, and anti-deamidated gliadin peptide IgG) and HLA genotypes.ResultsWe identified 2,247 children who were registered in the Danish National Patient Register with celiac disease. Duodenal biopsies for 1,555 of the children (69%) were registered in the Patobank; 1,127 (50%) had a biopsy that was compatible with celiac disease (ie, Marsh 2–3). We accessed the medical records of 95% of the children who were registered in the Danish National Patient Register with celiac disease. We found that 1,510 (67%) had one or more positive antibody-test results; 1,120 (50%) had anti-tissue transglutaminase 2, IgA at tenfold or greater the upper limit of the normal range and/or positive endomysial antibody results. The positive predictive value depended on the criteria used for validation and the types and numbers of registrations that were included in the analysis and ranged from 62% (95% confidence interval: 60%–64%) to 86% (95% confidence interval: 84%–87%).ConclusionOur findings indicate that the Danish National Patient Register is a valuable source to identify patients who have been diagnosed with celiac disease. However, validation of the diagnoses is warranted before data on the patients are used for research purposes.

Screening for Celiac Disease in Irritable Bowel Syndrome: An Updated Systematic Review and Meta-analysis.

Celiac disease (CD) and irritable bowel syndrome (IBS) share similar symptoms, leading to confusion between the two and diagnostic delay. International guidelines recommend screening individuals with IBS for CD, via serological testing. However, studies published recently have cast doubt on the utility of this. We updated a previous meta-analysis examining this issue. MEDLINE, EMBASE, and EMBASE Classic were searched through to May 2016. Eligible studies recruited adults with IBS according to symptom-based criteria, physician's opinion, or questionnaire data. Tests for CD included IgA-class antigliadin antibodies (AGA), endomysial antibodies (EMA), tissue transglutaminase antibodies (tTG), or duodenal biopsies following positive serology. The proportion of individuals meeting criteria for IBS testing positive for CD was combined to give a pooled prevalence for all studies, and compared between cases with IBS and, healthy controls without (where reported), using an odds ratio (OR) with a 95% confidence interval (CI). There were 36 eligible studies, recruiting 15,256 individuals, of whom 9,275 (60.8%) met criteria for IBS. Pooled ORs for positive IgA AGAs, EMA and/or tTG, and biopsy-proven CD in IBS subjects vs. controls were 3.21 (95% CI 1.55-6.65), 2.75 (95% CI 1.35-5.61), and 4.48 (95% CI 2.33-8.60), respectively. There was no increase in ORs for any test for CD among cases with IBS in North American studies, and results were inconsistent in population-based studies. The prevalence of biopsy-proven CD was significantly higher across all subtypes of IBS. Limitations included heterogeneity in some analyses, and few North American studies. Overall, prevalence of positive celiac serology and biopsy-proven CD was significantly higher in subjects with symptoms suggestive of IBS vs. healthy controls. However, the utility of screening for CD in individuals with suspected IBS in North America or in the community is less clear.

Real-Life Case Finding of Undiagnosed Celiac Disease: Exposing the Celiac Ugly Truth?

Introduction: Celiac disease (CD) is a common but underdiagnosed disorder. Case-finding (testing at-risk groups) is the preferred strategy for clinical detection. The primary aim was to estimate the frequency of indications for clinical testing in adults with undiagnosed CD and seronegative matched referents. The secondary aim was to estimate the frequency of actual clinical testing. Methods: Stored blood samples from 35,299 adults (age 18.1-87.7 years) with no prior diagnosis of CD were tested for tissue transglutaminase antibodies (tTGA). Samples with a positive/equivocal tTGA, defined as ≥3.0 U/ML, were tested for endomysial antibodies (EMA). Undiagnosed CD was defined by a positive EMA. 408 cases with undiagnosed CD were identified. From the tTGA negative individuals, 408 age and gender matched referents were selected. Medical records were systematically reviewed by a medical professional blinded to serology status, for indications for clinical testing, and evidence of clinical testing with serology and/or biopsies. Indications for clinical testing were consistent with the 2013 American College of Gastroenterology guidelines. Conditional logistic regression was used to test the association of case status and indications for clinical testing. Results: Eight matched pairs were excluded due to lack of data. 800 individuals were included (400 with undiagnosed CD and 400 referents), 61% female, median age of 44.2 years. The frequency of any indication for clinical testing was 159 (40%) among undiagnosed CD and 147 (37%) among referents (P=0.32). There was no difference in frequency of most indications for clinical testing among those with and without undiagnosed CD (Table 1). Hypothyroidism, dyspepsia, and chronic diarrhea were exceptions, with the former found more frequently among undiagnosed CD, and the latter two among referents. Frequency of clinical testing was low (2.3% among undiagnosed CD and 6.5% among referents; P=0.005).Table 1: Unadjusted Conditional Logistic Regression of Undiagnosed Celiac Disease and Indications for Clinical TestingConclusion: This is the largest study on real life case-finding in North America. Our study strongly suggests that the current paradigm for clinical detection of CD may not be effective, as most of the generally accepted indications for clinical testing failed to discriminate among persons with undiagnosed CD and matched referents. The study also confirms the low frequency of clinical testing for CD in the community. Clinical testing for CD, particularly with biopsies, was higher in referents, perhaps due to their higher rates of dyspepsia and chronic diarrhea.

PTU-117 Screening for Coeliac Disease in Irritable Bowel Syndrome Is Still Worthwhile: An Updated Systematic Review and Meta-Analysis

Introduction Coeliac disease (CD) and irritable bowel syndrome (IBS) may share similar symptoms, including bloating, abdominal pain, and diarrhoea. A previous meta-analysis demonstrated the prevalence of CD was higher in patients with IBS than controls without IBS, but recent studies have cast doubt on this. We therefore updated our previous meta-analysis. Methods MEDLINE and EMBASE were searched from 2008 (the date of a previous meta-analysis) up to February 2016. Relevant case series and case-control studies with unselected adults with IBS (+/- controls) were reviewed. IBS diagnosis was based on specific symptom-based criteria, physician’s opinion, or questionnaire data. Tests for CD included IgA antigliadin antibodies (AGA), tissue transglutaminase antibodies (tTG), endomysial antibodies (EMA), or dudoenal (D2) biopsies after positive IgA AGA, tTG, or EMA. The proportion of individuals meeting criteria for IBS testing positive for CD was combined, to give a pooled prevalence in all studies. For case-control studies the prevalence of a positive test for CD in both cases with IBS and controls without IBS were compared using odds ratios (OR) with a 95% confidence interval (CI). Results 10 studies used IgA AGAs to screen for CD in 4525 subjects, 2094 of whom had IBS. Pooled prevalence of positive IgA AGAs in IBS subjects was 5.7% (95% CI 1.7% to 11.8%). 7 of these were case-control studies and the odds ratio for a positive IgA AGA in 1530 IBS cases, compared with 2430 controls, was 2.97 (95% CI 1.42 to 6.18). 32 studies used EMA or tTG in 14150 subjects, 8219 of whom had IBS. Pooled prevalence of positive EMA or tTG was 2.6% (95% CI 1.6% to 3.8%). 12 of these were case-control studies and the odds ratio for a positive EMA or tTG in the 2677 IBS cases compared with 5931 controls was 2.60 (95% CI 1.41 to 4.79). 23 studies followed positive coeliac serology of any type with the offer of duodenal biopsy in 9784 individuals, 6991 of whom met criteria for IBS. Pooled prevalence of biopsy-proven CD in these studies was 3.3% (95% CI 2.3% to 4.5%). 8 of these were case-control studies and the odds ratio for biopsy-proven CD in 2025 IBS subjects compared with 2793 controls was 3.96 (95% CI 2.06 to 7.59). Conclusion Screening for CD in people with symptoms compatible with IBS is still worthwhile. Between 2.6% and 5.7% will have a positive serological test for CD, and 3.3% will have biopsy-proven CD. In all instances, the prevalence was significantly higher than in controls without IBS-type symptoms. Disclosure of Interest None Declared

OC-024 Does the Point of Care Test, Simtomax, Distinguish between Coeliac Disease and Non-Coeliac Gluten Sensitivity?: Abstract OC-024 Table 1

Introduction Non coeliac gluten sensitivity (NCGS) is an emerging clinical entity with a prevalence of 0.5–13%. It is characterised by gluten related symptoms with a negative coeliac serology and no villous atrophy (VA). It is currently a diagnosis based on exclusion of coeliac disease (CD). We aimed to assess the role of Simtomax, an IgA/G deamidated gliadin peptide (DGP) based point of care test (POCT), in differentiating between NCGS and CD. Methods Group 1: we compared the sensitivities of 3 POCTs: Simtomax, Biocard [IgA-tissue transglutaminase (TTG)] and Celiac Quick Test (IgA/G/M-TTG). We prospectively recruited 100 patients referred with a positive endomysial antibody (EMA) attending for a gastroscopy. All patients undertook the 3 POCTs, EMA, TTG, and all underwent a gastroscopy with 5 duodenal biopsies. Sensitivities were measured based on their histology. Group 2: the sensitivity of Simtomax in the general population was evaluated by prospectively recruiting 667 patients with gastrointestinal symptoms or ataxia attending for a gastroscopy. To reduce positive ascertainment bias, we excluded patients referred with a positive EMA, previous VA, known CD, self-reported gluten sensitivity, and those on a gluten free diet. All patients undertook Simtomax, EMA, TTG and a gastroscopy with 5 duodenal biopsies. Sensitivities were measured based on their histology. Group 3: we demonstrated the sensitivities of Simtomax in a gluten sensitive population. 35 patients with self-reported gluten sensitivity attending for a gastroscopy were prospectively recruited. All patients undertook Simtomax, EMA, TTG and a gastroscopy with 5 duodenal biopsies. Sensitivities were measured based on their histology. Results Group 1 showed that Simtomax was the best POCT in detecting CD. The CD prevalence was 85%. In group 2, the sensitivity and negative predictive value (NPV) of Simtomax were comparable to that of EMA and TTG. The prevalence of CD was 4.95%. In group 3, Simtomax had 100% sensitivity and NPV in differentiating between CD and NCGS. 4 patients (11.4%) were diagnosed with CD, 4 (11.4%) with potential CD (positive serology but no VA) and 27 (77.1%) with NCGS (negative serology and no VA). Conclusion Simtomax was the most accurate POCT for detecting CD. In a lower CD prevalence group 2 cohort, its sensitivity remained comparable to TTG and EMA. Simtomax had 100% sensitivity in detecting CD in patients with self-reported gluten sensitivity, and 100% NPV in identifying patients with NCGS. Disclosure of Interest M. Lau: None Declared, P. Mooney: None Declared, W. White: None Declared, M. Burden: None Declared, S. Wong: None Declared, M. Kurien: None Declared, D. Sanders Grant/research support from: Tillotts Pharma for investigator led studies in coeliac disease. None of the funding sources had any input in the study design, access to study data, interpretation of the findings or drafting of the abstract.