IgA Endomysial Antibodies Research Articles

Predictors of celiac disease in patients with type 1 diabetes and positive tissue transglutaminase immunoglobulin A.

Identify clinical and serologic features that more accurately predict a diagnosis of celiac disease (CD) in children with type 1 diabetes mellitus (T1DM), particularly focusing on the degree of elevation of tissue transglutaminase immunoglobulin A (TTG IgA) and dilution of positive endomysial antibody (EMA). We performed a single-center retrospective review of patients with T1DM who underwent endoscopy from 2016 to 2022 for evaluation of CD. We compared demographic, anthropometric, and laboratory data as well as symptoms and endoscopy findings for subjects with and without CD. Of 123 subjects who underwent esophagogastroduodenoscopy, 74 (60%) were diagnosed with CD. Univariate logistic regression analysis revealed the factors associated with CD were degree of TTG IgA elevation, EMA positivity, and degree of EMA dilution. For every 10-fold increase in TTG IgA, there was a 4.7× increased risk of CD. TTG IgA ≥10 times the upper limit of normal (ULN) provided a positive predictive value (PPV) of 85% (confidence interval [CI]: [0.76-92]) in all subjects and 91% in asymptomatic subjects (CI: [0.75-0.98]). Of 66 subjects with EMA data, 41 (62%) were positive and 32 had CD (PPV = 0.78). Of 12 asymptomatic subjects with positive EMA, eight had CD (PPV = 0.67). For subjects with EMA ≥ 1:80, all were diagnosed with CD, and all had TTG IgA ≥10 times the ULN. Among patients with T1DM, symptoms, adjunct labs, and anthropometrics do not help predict CD, but the degree of elevation of TTG IgA and dilution of a positive EMA result do.

Laboratory Testing for Celiac Disease: Clinical and Methodological Considerations.

Celiac disease (CeD) has an estimated prevalence of 1%-3%. The classical clinical presentation is malabsorption, but now patients may present with more subtle symptoms such as constipation, osteoporosis, or iron deficiency anemia. Children may also present with poor growth.CeD has a strong genetic component, and high-risk groups include first-degree relatives with CeD, patients with co-existing autoimmune diseases, and patients with chromosomal aberrations. Diagnostic tests for CeD include duodenal histology, serology, and genetic testing. Duodenal histology has traditionally been the gold standard of diagnosis. However, serological tests, especially IgA tissue transglutaminase antibodies (TTG-IgA), are widely used and diagnostic algorithms are based primarily on TTG-IgA as a starting point. Human leukocyte antigen typing may also be incorporated to determine genetic risk for CeD. Guidelines for children endorse biopsy avoidance provided high levels of TTG-IgA, with diagnostic accuracy being comparable to duodenal biopsy. Confirmation may be achieved by identifying IgA endomysial antibodies in a separate blood sample. Subjects with low positive TTG-IgA levels and subjects with IgA deficiency need a biopsy to establish a diagnosis of CeD. The clinical follow-up of CeD usually includes a repeat TTG-IgA examination. In adults, healing may be delayed or incomplete, and a rare consequence of refractory celiac disease is transformation to enteric T-cell lymphoma. Laboratory testing, in particular TTG-IgA, plays a central role in the diagnosis and has an accuracy comparable to histology. Diagnostic algorithms utilizing laboratory testing are critical for the development of novel strategies to improve diagnosis.

The differential diagnoses for severe enteropathy or severely damaged small intestinal mucosa.

The aim of this study was to explore the aetiology of severe duodenal mucosal abnormality in consecutive patients who underwent gastroscopy and duodenal biopsy over the past 10 years. A range of differential diagnoses have been reported for severe duodenal architectural distortion. Clinical and laboratory data of all the patients with severe duodenal architectural distortion diagnosed at MidCentral District Health Board (DHB), New Zealand were collected and statistically analysed. Ninety-five percent confidence intervals (CI) are shown. Between September 2009 and April 2019, 229 patients were diagnosed with severe enteropathy. The median patient age was 41 years (range 6-83 years). Two hundred and twenty-four of these patients (97.8%, 95.0-99.3%) were diagnosed with coeliac disease (CeD), with one of these patients having gluten induced T-cell lymphoma. From the remaining five patients, one had a diagnosis of tropical sprue and four did not have a clear aetiology. There were 180 patients from 191 (94.2%, 89.9-97.1%) with at least one positive coeliac marker, all with a diagnosis of CeD. Eleven patients (5.8% of 191, 2.9-10.1%) had negative markers for both tissue transglutaminase IgA (tTG-IgA) and IgA-endomysial antibodies (EMA-IgA) with six having a diagnosis of seronegative CeD. Although the spectrum of histological changes in CeD may range from normal to a flat mucosa, severe duodenal architectural distortion seems to occur mainly in CeD. Idiopathic enteropathy was recorded as the second but by far less frequent presentation of severe enteropathy. This study highlights that infection and other aetiologies are rarely implicated in severe enteropathy, with one case (0.4%) of refractory CeD/T-cell lymphoma.

Food and Celiac Disease Antibodies in Diarrhea-Predominant Irritable Bowel Syndrome

Background: Some foods can exacerbate the symptoms of irritable bowel syndrome (IBS), although the associations between the pathophysiology of IBS and IgG food antibodies levels are not well known. We examined IgG antibodies elicited in response to food and celiac disease in diarrhea-predominant IBS (IBS-D). Methods: Twenty patients with IBS-D and 20 healthy controls (HC), were enrolled. Serum immunoglobulin (Ig) G antibodies to 88 dietary items were measured and scored in accordance with the rate of antibody positivity. Serum tissue transglutaminase-IgA (tTG-IgA) and IgA endomysial antibody (EMA) were measured as markers of celiac disease. Serum IgE antibodies were also measured. Results: For the 88-item food-related IgG scores there was no significant difference in the number of dietary items with a ≥ 0.5 IgG score between the IBS and HC groups. Total IgG scores between groups were not significantly different. Scores for wheat, rye, and oats were not significantly different for the IBS versus the HC group. IgG scores for apples were significantly higher in the IBS versus the HC group. Serum tTG-IgA and EMA titers were negative in both groups and not significantly different between groups. Serum IgE was also not significantly different between groups. One patient with high titers for wheat, rye, and oats had duodenal mucosa histology classified as Marsh 1 and was negative for human leukocyte antigen DQ haplotypes HLA-DQ2/HLA-DQ8. Conclusions: We investigated IgG antibodies to food, tTG-IgA, and EMA in patients with IBS-D in whom IgG levels are likely influenced by dietary habits.

Clinical classification and long-term outcomes of seronegative coeliac disease: a 20-year multicentre follow-up study.

Seronegative coeliac disease is poorly defined. To study clinical phenotypes and long-term outcomes of seronegative coeliac disease in a multicentre cohort over 20years. Seronegative coeliac disease was diagnosed in HLA-DQ2/DQ8-positive patients with villous atrophy (VA), negative IgA endomysial (EmA), tissue transglutaminase (tTG) and deamidated-gliadin antibodies (DGP), clinical and histological response to a gluten-free diet (GFD), and no alternative causes for VA. In patients with IgA deficiency, coeliac disease was diagnosed through VA, positive IgG EmA/tTG/DGP and clinical/histological response to a GFD (coeliac disease+IgAd). Patients with seropositive coeliac disease served as controls. Of 227 patients previously diagnosed with seronegative coeliac disease, true seronegative coeliac disease was confirmed in 84, coeliac disease+IgAd in 48, and excluded in 55. Lack of follow-up duodenal biopsy precluded diagnosing seronegative coeliac disease in 40 patients. 2084 patients with seropositive coeliac disease served as controls. True seronegative coeliac disease had more severe symptoms at diagnosis and a higher risk of complications (HR 10.87, 95% CI 6.11-19.33, P<0.001) and mortality (HR 2.18, 95% CI 1.12-4.26, P<0.01) than seropositive coeliac disease. There were no differences between true seronegative coeliac disease and coeliac disease+IgAd. On multivariate analysis, age at diagnosis, lack of clinical response to a GFD, true seronegative coeliac disease, coeliac disease+IgAd, and classical presentation predicted complications. Age at diagnosis, complications and absence of clinical response to a GFD predicted mortality. Seronegative coeliac disease has a more aggressive disease phenotype than seropositive coeliac disease. These data argue against over-reliance on serology for the diagnosis of coeliac disease and support a strict clinical and histologic follow-up in seronegative coeliac disease.

Increased Prevalence of Celiac Disease in Patients with Cystic Fibrosis: A Systematic Review and Meta-Analysis.

Objectives: Immune regulation seems to be altered in cystic fibrosis (CF), thus potentially predisposing patients to developing autoimmune diseases (AID). In this meta-analysis, we aimed to evaluate the prevalence of celiac disease (CeD) among CF patients as by far the most commonly reported autoimmune disease in this population and, secondly, to review the observations on other, less frequently studied autoimmune diseases. Methods: We conducted a systematic literature search for studies that discussed AIDs among CF patients. Following standard selection and data collection, we calculated pooled raw prevalence with 95% confidence intervals (CI) for biopsy-verified CeD and seropositivity. Results: Out of the 21 eligible studies, 15 reported on CeD. Pooled prevalence of biopsy-verified CeD was 1.8% (CI 1.1–2.7%) according to a homogeneous dataset from six prospective, consecutive screening studies, while it proved to be 2.3% (CI 1.1–4.7%) according to a heterogeneous dataset from the other studies. Tissue transglutaminase IgA positivity was detected in 4.5% of CF cases (CI 2.8–6.9%), while tissue transglutaminase IgA–endomysial antibody IgA double positivity was found in 2.4% of them (CI 1.5–3.9%). Findings on other AIDs were strongly limited. Conclusions: The pooled prevalence of CeD in CF seemed to be more than twice as high compared to the global prevalence; therefore, routine screening of CeD could be considered in CF.

Serologic Testing for Celiac Disease in Graves’ Hyperthyroidism: Should We Act Early?

ABSTRACT Background: The general practice is to screen patients with autoimmune thyroid disease for celiac disease (CD); however, optimal timing for CD screening for patients with Graves’Disease (GD) has not been identified yet. The aim of the study was to show whether positive celiac antibodies persist after euthyroidism is achieved. Materials and Methods: Serum samples were collected from 35 patients with GD (23 female and 12 male) who applied to the endocrine outpatient clinic. Patients and healthy controls were screened for CD with IgG and IgA antigliadin antibodies (IgG – AGA and IgA – AGA), IgA endomysial antibody (IgA-EMA) and IgA tissue transglutaminase antibody (IgA anti-tTG). These antibodies were reevaluated when patients were euthyroid under antithyroid therapy. Small intestine biopsy was offered to the patients who remained antibody positive after being euthyroid. Results: Screening 35 patients with GD revealed positive results for IgA-AGA (n = 6/35, 17%), IgG-AGA (n = 9/35, 26%), IgA-EmA (n = 2/35, 6%) and IgA-tTG (n = 2/35, 6%). No patient had multiple antibodies positive. Selective IgA deficiency was not detected in patients and controls. When patients were euthyroid, baseline positive IgA-AGA, IgG-AGA, and IgA-EmA became negative, while positive anti-tTG persisted in two patients. Endoscopic duodenal biopsy showed a normal villi/crypts ratio in these patients. None of the controls had positive antibodies. Conclusion: Due to possibility of false seropositivity of celiac antibodies in patients with Graves’ thyrotoxicosis, one should defer testing for CD until euthyroidism has been achieved.

Prevalence of Coeliac Disease in Omani Adults with Iron Deficiency Anaemia of Unknown Cause: Case-finding study.

ObjectivesThis study aimed to estimate the serological prevalence of coeliac disease in patients with iron deficiency anaemia (IDA) of unknown cause at a primary healthcare facility in Oman.MethodsThis prospective case-finding study was conducted at the primary care clinics in Sultan Qaboos University Hospital, Muscat, Oman from September 2018 to June 2020. Patients aged 18 to 55 years, with a haemoglobin (Hb) level <11.5 g/dL for males and <11.0 g/dL for females and a ferritin level <30 ng/mL for males and <13 ng/mL for females, were included in the study. Blood samples were obtained for initial serological screening using serum immunoglobulin (Ig)A level; those samples with normal levels of IgA, IgA anti-tissue transglutaminase antibody (tTG) and IgA anti-deamidated gliadin peptide (DGP) were determined. Positive IgA-tTG test was confirmed using IgA-endomysial antibodies. Patients with low IgA levels were tested using IgG-tTG and IgG-DGP.ResultsA total of 104 patients participated in this study. Eight patients (7.7%) were found to have a positive serological screening result for coeliac disease; of these patients, three (37.5%) had a positive IgA-tTG result. Two of those three (66.7%) had a positive IgA-endomysial antibody. The IgA-DGP result was positive in seven (6.7%) of the 104 patients. Out of those seven patients, two also had a positive IgA tTG.ConclusionCoeliac disease is not a rare disorder. There is a need to increase awareness among healthcare professionals about coeliac disease and its non-classical manifestations such as IDA.

Automatic classification of IgA endomysial antibody test for celiac disease: a new method deploying machine learning

Widespread use of endomysial autoantibody (EmA) test in diagnostics of celiac disease is limited due to its subjectivity and its requirement of an expert evaluator. The study aimed to determine whether machine learning can be applied to create a new observer-independent method of automatic assessment and classification of the EmA test for celiac disease. The study material comprised of 2597 high-quality IgA-class EmA images collected in 2017–2018. According to standard procedure, highly-experienced professional classified samples into the following four classes: I - positive, II - negative, III - IgA deficient, and IV - equivocal. Machine learning was deployed to create a classification model. The sensitivity and specificity of the model were 82.84% and 99.40%, respectively. The accuracy was 96.80%. The classification error was 3.20%. The area under the curve was 99.67%, 99.61%, 100%, and 99.89%, for I, II, III, and IV class, respectively. The mean assessment time per image was 16.11 seconds. This is the first study deploying machine learning for the automatic classification of IgA-class EmA test for celiac disease. The results indicate that using machine learning enables quick and precise EmA test analysis that can be further developed to simplify EmA analysis.

Prevalence of Celiac Disease in a Long-term Study of a Spanish At-genetic-risk Cohort From the General Population.

To perform long-term celiac disease (CD) screening in an HLA-DQ2 (+) cohort from the general population and to assess the influence of risk genotypes on its development. In 2004, an HLA-DQ2 (+) cohort was selected. After the first CD screening at age 2 to 3 years, we performed a follow-up screening 8 to 10 years later. Antitransglutaminase 2 antibodies were determined using a rapid test kit. Results were confirmed by serum IgA antitransglutaminase 2 and IgA endomysial antibody determination. CD diagnosis was carried out by intestinal biopsies. Four HLA-DQ2 genotypic groups were used: G1: DQ2.5/DQ2.5 (G1A) or DQ2.5/ DQ2.2 (G1B); G2: DQ2.2/DQ7.5 (DQ2.5 trans); G3: DQ2.5/ X; G4: DQ2.2/X. CD prevalence after 10 years of follow-up was 5.8% (95% confidence interval 3.8-8.7). One of every 3 HLA-DQ2(+) children carried at least 1 haplotype DQ2.2 or DQ7. The homozygous genotype DQ2.5/DQ2.5 and the HLA-DQ2.5 trans genotype increased CD risk 4- and 3-fold, respectively. The homozygous genotype DQ2.5/ DQ2.2 did not increase the CD risk. Children carrying G1 or G2 genotypes were diagnosed with CD earlier and more frequently during the follow-up compare with those carrying G3 or G4 genotypes. Approximately 81% of children with spontaneous antibody negativization after the first screening maintained negative antibodies. A repeated screening of at-risk children during their follow-up allowed us to diagnose new CD cases. In our cohort, HLA- DQ2.5 trans genotype conferred a higher risk in the development of CD than HLA- DQ2.5/DQ2.2. The majority of children with potential CD and CD autoimmunity at 10 years of age remained healthy.

Office-Based Point of Care Testing (IgA/IgG-Deamidated Gliadin Peptide) for Celiac Disease

Celiac disease (CD) is common yet under-detected. A point of care test (POCT) may improve CD detection. We aimed to assess the diagnostic performance of an IgA/IgG-deamidated gliadin peptide (DGP)-based POCT for CD detection, patient acceptability, and inter-observer variability of the POCT results. From 2013-2017, we prospectively recruited patients referred to secondary care with gastrointestinal symptoms, anemia and/or weight loss (group 1); and patients with self-reported gluten sensitivity with unknown CD status (group 2). All patients had concurrent POCT, IgA-tissue transglutaminase (IgA-TTG), IgA-endomysial antibodies (IgA-EMA), total IgA levels, and duodenal biopsies. Five hundred patients completed acceptability questionnaires, and inter-observer variability of the POCT results was compared among five clinical staff for 400 cases. Group 1: 1000 patients, 58.5% female, age 16-91, median age 57. Forty-one patients (4.1%) were diagnosed with CD. The sensitivities of the POCT, IgA-TTG, and IgA-EMA were 82.9, 78.1, and 70.7%; the specificities were 85.4, 96.3, and 99.8%. Group 2: 61 patients, 83% female; age 17-73, median age 35. The POCT had 100% sensitivity and negative predictive value in detecting CD in group 2. Most patients preferred the POCT to venepuncture (90.4% vs. 2.8%). There was good inter-observer agreement on the POCT results with a Fleiss Kappa coefficient of 0.895. The POCT had comparable sensitivities to serology, and correctly identified all CD cases in a gluten sensitive cohort. However, its low specificity may increase unnecessary investigations. Despite its advantage of convenience and rapid results, it may not add significant value to case finding in an office-based setting.

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.

Prevalence of Occult Celiac Disease in Females with Iron Deficiency in the United States: An Nhanes Analysis.

Aim:The prevalence of celiac disease in patients with iron deficiency (ID) in the United States is unknown. Estimating the prevalence of Celiac disease (CD) in patients with ID could help to determine the need to screen these patients for occult CD. In 2017, the United States Preventive Services Task Force stated that the current evidence is inadequate to assess the balance of benefits and harms of screening for CD in asymptomatic persons. Also, there are no current guidelines to advise physicians regarding the screening of patients with iron deficiency for occult CD.Methods:Data were obtained from the National Health and Nutrition Examination Survey (NHANES) database, a nationally representative health survey conducted from 2009 to 2010. We included 2,105 females aged 6 years or older. Iron deficiency was defined as serum ferritin level <20 ng/ml, and patients were considered positive for celiac disease when positive for both immunoglobulin A tissue transglutaminase antibody (IgA Ttga) and IgA endomysial antibody (IgA EMA). Subjects with Iron deficiency were divided into two groups (ID and Non-ID). The association of CD and ID, i.e., the primary outcome, was obtained after adjusting other covariates using logistic regression.Results:The mean age of our study population was 29.7 years; 28.0 years in the ID group and 30.3 in the non-ID group (p<0.001). Non-Hispanic whites constituted 41%of the total study sample. The demographic characteristics of the study population are shown in table 1.There were 569 (27%) females who had ID and 1536 (73%) who did not have ID. The overall prevalence of CD in the study population was 0.33% (7/2105). The prevalence of CD in ID females was 0.9% (5/569), and the prevalence of CD in non-ID females was 0.1% (2/1536) with an odds ratio (OR) of 6.79 (95% confidence interval, 1.31-35.2). After adjusting for selected covariates, the prevalence of CD was higher in female subjects with ID with OR of 12.5 (95% CI 1.74-90). Although these results showed that CD did increase the risk of having ID in females, it did not show any difference in hemoglobin between celiac positive and celiac negative females with an odds ratio of 1.75 (95% CI 0.61-5.05).DiscussionIn this study, one in 113 iron-deficient females met the criteria for the diagnosis of occult CD compared to one in 676 non-iron deficient females. So, screening for occult CD could help in diagnosing the cause of ID and subsequently help in treatment. Celiac serology offers a non-invasive test to detect gluten hypersensitivity in females with ID. There is no study looking into the downside of screening for CD in asymptomatic people. However, potential disadvantages of CD screening may include increased anxiety, over-diagnosis, unnecessary serologic tests and increased need for unnecessary endoscopies with biopsy.The strength of this study is that it includes a representative sample from a national database, which was adjusted for minority groups. However, this study also had several limitations. The number of cases of CD was very small due to the relatively low prevalence of CD in the United States (0.71%). Another limitation was our criteria for the diagnosis of CD based on serology only without histological confirmation, as a duodenal biopsy is an invasive test difficult to perform in a population-based study. However, this limitation is partially balanced by the sequential serological testing of IgA EMA in IgA tTGA positive individuals. Another potential limitation is that patients with IgA deficiency were missed by the study as IgA deficiency was not tested.Conclusions:Although the overall prevalence of celiac disease in the United States is low in the female population, the prevalence is higher in subjects with Iron deficiency. We suggest that CD testing should be considered in patients with refractory ID when other obvious causes have been ruled out. Further prospective studies are needed to validate this finding. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

The Role of an IgA/IgG-Deamidated Gliadin Peptide Point-of-Care Test in Predicting Persistent Villous Atrophy in Patients With Celiac Disease on a Gluten-Free Diet.

Mucosal healing is important in celiac disease (CD) for the prevention of complications. However, obtaining duodenal biopsies is invasive, and there is currently no reliable surrogate marker for histological remission in clinical practice. We aimed to assess the role of a point-of-care test (POCT) based on IgA/IgG-deamidated gliadin peptide, in detecting persistent villous atrophy (VA) in CD. We prospectively recruited patients with CD attending endoscopy for the assessment of histological remission. All patients had IgA-endomysial (EMA) antibodies, IgA-tissue transglutaminase (TTG) antibodies, and the POCT performed, and completed a validated dietary adherence questionnaire. A gastroscopy was performed in all patients, with four biopsies taken from the second part of the duodenum and one from the duodenal bulb. We compared the diagnostic performance of the surrogate markers against duodenal histology as the reference standard. A total of 217 patients with CD (70% female, age range 16-83 years, median age 53 years) on a gluten-free diet (median duration 6 years) were recruited from 2013 to 2017. Eighty-five (39.2%) patients had persistent VA. The sensitivities of the POCT, TTG, EMA, and the adherence score in detecting VA were 67.1%, 44.7%, 37.7%, and 24.7% respectively (P=0.0005). The combination of the POCT and adherence score only marginally increased the sensitivity to 70.6% (59.7-80.0%). The sensitivity of the POCT was higher than the other surrogate markers in predicting VA. A POCT may provide the additional advantage of an immediate objective assessment of mucosal healing at the time of an office-based follow-up consultation.

Screening for celiac disease, by endomysial antibodies, in patients with unexplained hypertransaminasaemia

Objective: To do a serological screening for celiac disease in patients with unexplained liver cytolysis.Materials and methods: Fifty-six patients with liver cytolysis without known aetiology were studied. Endomysial antibodies were determined by indirect immunofluorescence on human umbilical cord. Two thousand and five hundred blood donors served as control group. For statistical analysis, we used Chi-square or Fisher’s exact test.Results: The frequency of IgA endomysial antibodies in our patients was significantly higher than in the control group (8.92% vs. 0.28%, p < .001). In female, endomysial antibodies were significantly more frequent in patients than in healthy subjects (12.12% vs. 0.4%; p < .001). In male, endomysial antibodies were significantly more frequent in patients than in healthy subjects (4.34% vs. 0.22%; p = .006). The frequency of positive EMA in female patients was higher than in male, but the difference was not statistically significant (12.12% vs. 4.43%; p = .6). Two patients were non-compliant with the gluten-free diet. One patient was out of touch. For the two other patients, transaminase levels reverted to normal level within six months of strict gluten withdrawal.Conclusions: A screening for celiac disease should be included within the diagnosis protocol of liver cytolysis.

Short article: Mortality and differential diagnoses of villous atrophy without coeliac antibodies.

Villous atrophy (VA) of the small bowel is mainly related to coeliac disease (CD), whose diagnosis is made on the basis of positive endomysial/tissue transglutaminase antibodies while on a gluten-containing diet in the vast majority of patients. However, VA can also occur in other conditions whose epidemiology is little known. Our aim was to study the epidemiology and clinical features of these rare enteropathies. Clinical and laboratory data of all the patients with VA directly diagnosed in our centre in the last 15 years were collected and statistically analysed. Between September 1999 and June 2015, 274 patients were diagnosed with VA. A total of 260 patients were also positive to coeliac antibodies; the other 14 had VA, but no IgA endomysial antibodies: five had common variable immunodeficiency, three had dermatitis herpetiformis, two had IgA deficiency associated with CD, one had abdominal lymphoma, one had unclassified sprue, one had olmesartan-associated enteropathy and one had seronegative CD. Mortality was 6.0 deaths per 100 person years (95% confidence interval: 2.2-16) in patients with VA but negative coeliac antibodies, whereas only 0.2 deaths per 100 person years (95% confidence interval: 0.1-0.6) occurred in coeliac patients. Patients with VA and negative endomysial antibodies are rare. However, these forms of VA identify specific causes that can be diagnosed. These patients are affected by a very high mortality.

One‐step immunochromatographic visual assay for anti‐transglutaminase detection in organ culture system: An easy and prompt method to simplify the in vitro diagnosis of celiac disease

Anti-tissue transglutaminase (anti-tTG) and endomysium antibodies (EMA) are detectable in duodenal culture media of celiac disease (CD) patients. To improve the management of this organ culture system, we evaluated the anti-tTG occurrence by immunochromatographic assay (ICA). A total of 103 CD patients and 41 disease controls underwent duodenal biopsy for the organ culture. In culture supernatants, IgA anti-tTG were tested by both enzyme-linked immunosorbent assay (ELISA) and ICA, IgA EMA were searched by indirect immunofluorescence analysis (iIFA). Endomysium antibodies and anti-tTG measured by ELISA were positive in culture media of all CD patients, while anti-tTG detected by ICA were positive in culture media of 87/103 CD patients. Anti-tTG ICA scores significantly correlated with anti-tTG ELISA values (r=.71, P<.0001). Sensitivity, specificity and diagnostic accuracy of anti-tTG detected by ICA were 84.5%, 100% and 88.9%, respectively. Using ICA, anti-tTG are detectable in duodenal culture media of most CD patients and the intensity of indicative lines depends on the anti-tTG concentration. Sensitivity and diagnostic accuracy achieved with ICA are lower than those obtained with ELISA but, given that the first is a more easy and prompt method, data suggest the possibility of utilizing it in the in vitro diagnosis of CD.

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.

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

PWE-058 The Role of A Point of Care Test, Simtomax, in Predicting Histological Remission in Coeliac Disease on A Gluten Free Diet: Abstract PWE-058 Table 1

Introduction Coeliac disease (CD) is a chronic inflammatory enteropathy treated with a gluten free diet (GFD). Clinical symptoms and complications of CD are thought to be associated with ongoing duodenal inflammation due to continued gluten exposure, hence the optimal assessment of response to a GFD is histological remission. However, there is little consensus in the UK on routine re-biopsy during follow up. Duodenal biopsy requires a gastroscopy which is invasive and can be poorly tolerated. Coeliac serology and dietetic evaluation have been used as surrogate markers for histological remission, but the correlation has been shown to be poor. We aimed to assess the role of an IgA/G-deamidated gliadin peptide (DGP) based point of care test (POCT), Simtomax, in predicting histological remission in CD. Methods We prospectively recruited patients with known CD attending for a gastroscopy with duodenal biopsy for the assessment of disease remission. All patients underwent a blood test for IgA-endomysial antibodies (EMA), IgA-tissue transglutaminase antibodies (TTG), total IgA levels and Simtomax at the point of endoscopy. They also completed a validated GFD adherence questionnaire (Biagi) which gives a 5 point score (0–4), with the highest score indicating strict adherence to a GFD. Patients with an adherence score of 3 or 4 were considered to follow a strict GFD. A gastroscopy was then performed with quadrantic biopsies taken from the second part of the duodenum and one biopsy taken from the duodenal bulb. We compared all surrogate markers to the gold standard of duodenal histology. Results 145 (74% female, median age 53) patients with CD on a GFD were recruited from 2013–2015. 52 (36%) patients had persistent villous atrophy. Simtomax was the most sensitive in predicting villous atrophy (78.8%). The sensitivities of EMA, TTG and the GFD adherence score were significantly lower than that of Simtomax. Simtomax had the best negative predictive value (NPV) for villous atrophy at 82.5%. Conclusion Simtomax exceeds all other available surrogate markers in predicting the presence of villous atrophy. Simtomax could be used to aid informed decision making in patients who require but are reluctant to undertake a gastroscopy for duodenal biopsy to assess for disease remission. It could also act as a useful adjunct to identify patients who may require further dietetic support. 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.