Duodenal Biopsies In Patients Research Articles

Predictors of Subsequent Celiac Disease Seropositivity in Patients Diagnosed with Duodenal Villus Atrophy on Upper Endoscopy.

The diagnosis of celiac disease (CD) is based on positive IgA autoantibodies to tissue transglutaminase (TTG IgA) and confirmatory histopathology demonstrating duodenal villus atrophy (VA). Diagnostic challenges can occur when VA is found on duodenal biopsies in patients without prior CD serologies. To characterize the predictors of CD seropositivity in patients with VA on biopsy without prior CD serologies. We performed a retrospective cohort study of patients found to have duodenal VA on histopathology from 2010 to 2020 who did not have prior CD serologies measured and who had them checked after their biopsy. Patients with known or suspected CD prior to their duodenal biopsy were excluded. Of 162 patients with VA and no prior CD serologies, 50 (31%) subsequently had an elevated TTG IgA consistent with CD. Patients with an elevated TTG IgA were more likely to be non-Hispanic (76% vs. 42%; p < 0.001), white (74% vs. 62%; p=0.025), and younger (ages 18-39, 26% vs. 12%; p=0.002) compared to those with a negative TTG IgA. By contrast, these patients were less likely to present in middle adulthood (ages 40-59, 6% vs. 29%; p= 0.002). The most common identified etiologies of seronegative VA were Crohn's disease (13%), seronegative CD (8.9%), H. pylori infection (6.3%), tropical sprue (5.4%), and olmesartan-related enteropathy (3.6%). Age and ethnicity may be helpful when stratifying the likelihood of CD in the absence of supporting serologies. A majority of patients (69%) diagnosed with VA without prior CD serologies have negative serologies, consistent with seronegative CD or the spectrum of non-celiac enteropathies for which further evaluation is needed.

Brunner gland inflammation in Crohn's disease and Celiac disease: Overlapping inflammatory patterns suggest a possible link

Similar to celiac disease, inflammatory bowel disease frequently manifests in the duodenum. Histopathologic studies focused on mucosal alterations with little attention to submucosal Brunner glands. Recently, several studies have demonstrated overlapping features between Crohn's disease and celiac disease suggesting a putative link. However, histopathologic studies evaluating this possible link are limited, and those that are focused on Brunner glands are lacking. The present study aims to explore whether Crohn's disease and celiac disease display shared or overlapping inflammatory changes in Brunner glands. We performed a retrospective review study over 17-years retrieving duodenal biopsy specimens containing Brunner gland lobules in patients with Crohn's disease, celiac disease, and ulcerative colitis. We found 10 out of 126 duodenal biopsies (8 %) in patients with Crohn's disease and 6 out of 134 (4.5 %) duodenal biopsies in patients with celiac disease sharing inflammatory patterns in duodenal Brunner gland lobules. Both diseases showed interstitial intralobular and interlobular mixed chronic inflammation with variable fibrosis. Focally enhanced active inflammation of Brunner gland lobules was more characteristic of Crohn's disease. Intralobular epithelioid granulomas and multinucleated giant cells were specific to Crohn's disease. Ulcerative colitis patients did not show similar features. The interstitial focally enhanced chronic inflammatory pattern was significantly (p < 0.05) associated with both diseases, while the other inflammatory patterns were not (p > 0.05). This overlapping inflammatory pattern in Brunner glands in patients with Crohn's disease and celiac disease is supportive of the previously reported link between the two diseases. Pathologists should pay more attention to Brunner glands when evaluating duodenal biopsies. Further studies are warranted to validate these observations and their relevance in the pathogenesis of autoinflammatory gastrointestinal diseases.

A Study of Duodenal Biopsy in Patients with Anemia - An Experience at a Rural Based Tertiary Care Hospital

A Study of Duodenal Biopsy in Patients with Anemia - An Experience at a Rural Based Tertiary Care Hospital

Celiac Disease Diagnosis Via Histopathological Correlation of Duodenal Biopsies in Children

Aim: The purpose of this study is to compare the diagnostic accuracy of duodenal bulb biopsies to distal duodenal biopsies in patients suspected of having celiac disease. Study Design: Cross-sectional study Place and Duration: This study was conducted at Department of Pathology, The children's hospital &amp; The institute of child health, Multan during the period from April, 2022 to September, 2022. Methods: Total 86 children of celiac disease were presented in this study. Informed written consent provided by parents of children for the collection of detailed demographic data. Under general anaesthesia, a duodenal bulb sample and four distal duodenum samples were collected during an upper gastrointestinal endoscopy. Histological alterations indicative with CD were identified. Histological diagnosis and grading were performed using a modification of the Marsh-Oberhuber classification. The entire data set was analyzed by using SPSS 20.0. Results: Forty nine (56.97%) patients were females and 37 (43.03%) cases were males. Children’s mean age was 6.4±3.27 years with mean weight 15.9±6.19 kg. Mean height of the cases was 94.7±10.42 cm. There were 51 (59.3%) children had urban residency. According to marsh grading, 50 (58.1%) cases had grade IIIC. We found that frequency of crypt hyperplasia, influx of immune cells in lamina propria and enterocytes change in both duodenal bulb and distal part biopsies were equal while only frequency of villous atrophy and intraepithelial lymphocytes were different in both biopsies. 96.5% patients reported a high level of correlation, while only 3.5% reported no correlation. Conclusion: Both biopsy sites agree strongly. We may now suggest duodenal bulb biopsy alone. Since the endoscopic method of distal duodenum is laborious and requires more knowledge and time, obtaining biopsies from the proximal section is easier and requires less experience, therefore this strategy may be used even at facilities with junior paediatric gastroenterologists. Keywords: Celiac disease, Children, Histopathology, Duodenal bulb, Distal duodenum

Diagnostic utility of endoscopic duodenal biopsies and histopathological finding in upper gastrointestinal diseases: A 2-year analysis

Background: Diseases of gastrointestinal (GI) tract present wit myriad signs and symptoms. Appropriate management of these diseases involves proper evaluation. Upper GI endoscopies are becoming increasingly popular because it helps in first localizing the lesion and then biopsy specimens can be obtained from affected area. Duodenal biopsy followed by histopathological examination may clinch the diagnosis in majority of the cases. Aims and Objectives: The aim of the study was to find out diagnostic utility of endoscopic duodenal biopsies and histopathological finding in the upper GI diseases. (1) To analyze duodenal endoscopic biopsy samples obtained from patients presenting with the upper GI symptoms. (2) To correlate endoscopic and histopathological findings in studied cases. Materials and Methods: A retrospective and prospective observational study was carried out at the private histopathology center over a period of 2 years. All the patients underwent upper GI endoscopy with duodenal biopsies using flexible endoscope. Histopathology of the samples obtained from endoscopic duodenal biopsies in patients presenting with the upper GI symptoms were analyzed. The endoscopic findings such as mass lesion or ulcerative lesion were correlated with histopathological findings. Results: Out of these 704 biopsies, 303 (43.04%) were esophageal biopsies, 220 [31.25%] were gastric, and 181 [25.71%] were duodenal biopsies. There were 129 (71.27%) males and 52 (28.73%) females with a M: F ratio of 2.5: 1. The mean age of the cases was found to be 54.7±12.32 years. Out of 181 biopsies which were performed in this study, 100 (55.25%) lesions were found to be having neoplastic etiology whereas 81 (44.75%) lesions were found to have non-neoplastic etiology. Among patients who were found to have duodenal growth on endoscopy well differentiated adenocarcinoma (15.47%) followed by moderately differentiated adenocarcinoma (6.63%) were the common pathologies. In cases of non-neoplastic etiology, non-specific duodenitis was most common pathology (17.13%). Conclusion: Endoscopic biopsy followed by histopathological examination is cornerstone of the management of patients presenting with intractable upper GI symptomatology.

Frequency of Celiac Disease Diagnosed on Endoscopic Duodenal Biopsy in Patients of Functional Dyspepsia

Objective: To determine the frequency of celiac disease diagnosed on endoscopic duodenal biopsy in patients presenting with functional dyspepsia. Methods: This was a cross-sectional study was conducted at the Department of Gastroenterology and Hepatology, Shalamar Medical and Dental College, Lahore. A total 160 patients of either gender, aged 20-70 years and diagnosed with functional dyspepsia were included. The study was conducted during a period of six months from September 2021 to February 2022. The informed consent of patients was obtained. All the basic demographic information of each patient was noted and all the patients underwent endoscopic duodenal biopsies and specimens were sent to the department of histopathology for the histopathological assessment of celiac disease. The collected data were analyzed statistically by using SPSS version 12. Results: Average age of male and female patients was 45.61±14.41 and 39.83±14.91 years. Among 160 patients 60(37%) were male and 100(63%) were females. There were 90(56.3%) patients who had dysmotility like dyspepsia, 54(33.8%) patients diagnosed with an ulcer like dyspepsia and 16(10%) patients were having unspecified dyspepsia. According to the Marsh classification, 140 patients were diagnosed with type-0, 7 patients with Type-1, 2 patients with type-2, 9 patients with type-3a and 2 patients with type-3b. Celiac disease was diagnosed with the help of Modified Marsh classification. Among 160 patients 13(8%) were diagnosed with celiac disease. Conclusion: The results of the current study show a high frequency of celiac disease in patients with functional dyspepsia. Keeping this fact in mind, silent/subclinical CD should be kept in mind as a cause of functional dyspepsia during clinical activities Keywords: Celiac disease, Endoscopic duodenal biopsy, Functional dyspepsia

Low Prevalence of Extraesophageal Gastrointestinal Pathology in Patients with Eosinophilic Esophagitis.

Limited data are available to support current guidelines recommendations on obtaining gastric and duodenal biopsies of patients with clinical and histologic manifestations consistent with eosinophilic esophagitis (EoE) to rule out eosinophilic gastritis (EG) or duodenitis (EoD). Our study examined the prevalence of concomitant extraesophageal, gastrointestinal pathology to better characterize the diagnostic yield of additional biopsies. This was a single-center, retrospective study which utilized ICD 9 codes (530.13) and search queries of pathology reports ("Eosinophilic esophagitis," "EoE") to identify EoE patients. Patient endoscopy reports, pathology reports, and office notes were manually reviewed to characterize cases. The electronic health record search yielded 1,688 EoE adults. In those who had extra-esophageal biopsies obtained, EG was identified in 34 (3.4%), H. pylori in 45 (4.6%), EoD in 27 (3.3%), and histology consistent with celiac disease in 20 (2.5%). Endoscopic abnormalities were found in the stomach of 92% of patients with EoE and EG and in the duodenum of 50% of patients with EoE and EoD. Symptoms of dyspepsia and/or abdominal pain occurred in a significantly greater proportion of patients with extraesophageal disease (64% vs. 19% in EoE group, p < 0.001). Overall, extraesophageal pathology would have been missed in 1.4% of patients lacking either symptoms or endoscopic signs suggestive of extraesophageal disease. The yield of gastric and duodenal biopsies in adults with EoE is low, with 6.5% of patients demonstrating histologic features of celiac disease, Helicobacter pylori, EG, and/or EoD. Biopsies of extraesophageal, gastrointestinal sites in patients with suspected or previously diagnosed EoE should consider symptom and endoscopy manifestations as well as the potential impact of histopathologic findings on clinical management.

S3146 Patients With Eosinophilic Esophagitis (EoE) and Persistent Extra-Esophageal GI Symptoms Should Be Evaluated for Eosinophilic Gastritis (EG) and Eosinophilic Duodenitis (EoD)

INTRODUCTION: Eosinophilic gastrointestinal (GI) disorders (EGIDs) are chronic inflammatory conditions characterized by aberrant accumulation and activation of localized tissue eosinophils and mast cells. While Eosinophilic Esophagitis (EoE) is the best understood of the EGIDs, there is growing understanding of Eosinophilic Gastritis (EG) and Duodenitis (EoD) and evidence that they may be more prevalent than previous estimates. Though EoE is defined in part by esophageal dysfunction, patients with EoE often present with extra-esophageal symptoms which may not be attributable to isolated esophageal inflammation. EG/EoD may be underdiagnosed in these patients due to non-routine biopsy and histopathologic evaluation of gastric and duodenal mucosa. We reviewed gastric and duodenal biopsies in patients with known EoE and persistent non-esophageal symptoms to determine the frequency of EG/EoD in this population. METHODS: 27 patients at the University of Utah with a known history of EoE, persistent extra-esophageal symptoms, and a history of gastric and duodenal biopsies were identified, and retrospectively reviewed. Histopathologic evaluation was performed and eosinophil counts and chronic inflammation were assessed. Eosinophilic gastritis and duodenitis were defined as the presence of ≥30 eosinophils/high-powered field (hpf) in 5 and 3 hpfs in the stomach and duodenum, respectively. RESULTS: Of the 27 patients, 17 (63%) met histologic criteria for EG and/or EoD (4 combined EG/EoD, 13 EoD). The most common non-esophageal symptoms among these 17 patients were abdominal pain, nausea and bloating. 3 of the 17 patients had been diagnosed with irritable bowel syndrome in addition to EoE. Of the 10 patients not meeting histologic criteria for EG/EoD, 4 were subsequently found to have gastroparesis, 1 was on high dose NSAIDs and 1 was subsequently found to have mast cell activation syndrome. CONCLUSION: In this retrospective study, 63% of patients with EoE and chronic extra-esophageal GI symptoms were found to meet histologic criteria for EG/EoD. This high discovery rate suggests that gastric and duodenal biopsies should be performed and evaluated for eosinophils in patients with EoE and extra-esophageal symptoms, including those with persistent abdominal pain, nausea, bloating or a diagnosis of functional GI disease.

Histomorphological study of duodenum with special reference to RUT (Rapid Urease Test) negative dyspepsia in a rural care setting

Introduction:In our institute duodenal biopsies are taken in patients having either, unexplained anemia, weight loss, recurrent loose stool, abdominal pain, dyspepsia or suspected malabsorption. In the present study we have evaluated histomorphological features of duodenal biopsies in patients presented with specifically Rapid Urease Test (RUT) negative dyspepsia. Materials and Methods: A retrospective observational study was conducted and data of duodenal biopsies were collected from January 2017 to December 2018. Histopathology slides of duodenal biopsies were reevaluated. We have correlated clinical and endoscopic findings with various histomorphological parameters. Results: We have included total 99 cases. Demographic profile of our study population shows wide age range (9 years to 74 years) with mean age 39.8 years and Male: Female ratio 1.1:1. Dyspepsia was the common presenting symptoms (64.6% cases) and malabsorption was suspected in 29 cases. 28.3% cases show villous architectural abnormalities which correlate significantly with endoscopic findings of duodenal nodularity. Moderate to severe lamina propria lympho-plasmacytic infiltration seen in 58.56% cases and correlates significantly with dyspeptic symptoms. Duodenal biopsy was diagnostic in 3% cases. Conclusion: Diagnostic yield of duodenal biopsy is low but informative with proper clinical background.

RNA sequencing of intestinal mucosa reveals novel pathways functionally linked to celiac disease pathogenesis.

Background & aimsThe early steps in the pathophysiology of celiac disease (CD) leading to loss of tolerance to gluten are poorly described. Our aim was to use RNA sequencing of duodenal biopsies in patients with active CD, CD in remission, and non-CD controls to gain insight into CD pathophysiology, identify additional genetic signatures linked to CD, and possibly uncover targets for future therapeutic agents.MethodsWe performed whole transcriptome shotgun sequencing of intestinal biopsies in subjects with active and remission CD and non-CD controls. We also performed functional pathway analysis of differentially expressed genes to identify statistically significant pathways that are up or down regulated in subjects with active CD compared to remission CD.ResultsWe identified the upregulation of novel genes including IL12R, ITGAM and IGSF4 involved in the immune response machinery and cell adhesion process in the mucosa of subjects with active CD compared to those in remission. We identified a unique signature of genes, related to innate immunity, perturbed exclusively in CD irrespective of disease status. Finally, we highlight novel pathways of interest that may contribute to the early steps of CD pathogenesis and its comorbidities such as the spliceosome, pathways related to the innate immune response, and pathways related to autoimmunity.ConclusionsOur study confirmed previous findings based on GWAS and immunological studies pertinent to CD pathogenesis and describes novel genes and pathways that with further validation may be found to contribute to the early steps in the pathogenesis of CD, ongoing inflammation, and comorbidities associated with CD.

Correlation of Serum Tissue Transglutaminase Antibody Levels and Marsh Grading of Duodenal Biopsy in Patients of Celiac Disease

Background: Celiac disease (CD) is a chronic small intestinal immune-mediated enteropathy precipitated in genetically predisposed individuals by ingestion of wheat gluten and related proteins of barley and rye. It is an under-diagnosed gluten-sensitive enteropathy, usually presenting with atypical/extra-intestinal features. Duodenal biopsy is considered as the gold standard in the diagnosis of CD. Serum anti tissue transglutaminase (anti-tTG) antibodies is auto antibodies directed against tissue transglutaminase (tTG) enzyme. Aims and objective: The aim of the study is to find out the prevalence of CD among clinically suspected cases of malabsorption, to assess the correlation of anti-tTG levels with modified Marsh grading of duodenal biopsy, to find out sensitivity, specificity and predictive values of anti-tTG test and to calculate the cut off values of anti-tTG diagnostic of high grade CD. Methodology: The present study included 118 clinically suspected patients of malabsorption in which both duodenal biopsy and anti-tTG test was done. The mucosal damage graded according to the modified Marsh grading and anti-tTG tests were done in serum using ELISA kit. Results: The prevalence of CD among clinically suspected cases of malabsorption was 12.7%. The incidence was highest in middle aged male patients. The most common clinical symptom was chronic diarrhea and commonest presenting sign was anemia. Anti-tTG levels were found to be proportionately increasing with the severity of CD and showed a positive correlation(r=0.433). Patients with anemia and chronic diarrhea showed statistically significant (p value=0.0242 and 0.0089 respectively) mean anti-tTG levels in Celiac patients in relation to non-Celiac patients. Although the mean levels of anti-tTG was 6.3 times higher than baseline in grade 3 disease, the ROC analysis showed that anti-tTG in isolation had no significance in exactly grading the disease (AUC=0.30). Conclusion: Positive correlation was found between anti-tTG levels and modified Marsh grading. Anti-tTG showed proportionate increase with severity of duodenal damage. Anti-tTG test showed low sensitivity (42.86%) and high specificity (84.34%). Hence it is not a reliable tool in isolation to screen CD but should be used in combination with duodenal biopsy. It can be used to assess the severity of CD and for follow up.

The Utility of Routine Endoscopic Distal Duodenal Biopsy in Patients with Irritable Bowel Syndrome for Celiac Disease Diagnosis; First Study from Nepal

Aim: To investigate the utility of routine endoscopic distal duodenal biopsy in patients with Irritable Bowel Syndrome (IBS) for the diagnosis of Celiac Disease (CD). Method: This study was conducted at the outpatient Department of Gastroenterology at the Institute of Medicine, Tribhuvan University, Kathmandu, Nepal. One hundred patients with IBS selected by Rome III Criteria were prospectively evaluated from April 2015 through March 2016. Esophagogastroduodenoscopy (EGD) was performed on all patients, with four-quadrant distal duodenal biopsies obtained from each patient. The biopsy sections were studied for Marsh-type histology, a histology characteristic of CD. Patients with Marsh-type histology had Immunoglobulin-A anti-tissue transglutaminase (IgA anti tTG) serology ordered, were recommended to start a gluten-free diet (GFD), and were followed up in clinic in 3-6 weeks. The prevalence of CD (defined as Marsh histology grade I-III with serology positive responding to GFD) was calculated in patients with IBS as a whole and among IBS subtypes. Statistical analysis was done using SPSS version 19 software (Chicago, IL, USA). Results: Of the 100 IBS patients evaluated, 50 patients had abnormal duodenal histology. Among these 50 patients, 13 had Marsh-type histology, and the remaining 37 had non-specific duodenitis. Of the 13 patients with Marsh-type histology, 4 were seropositive for CD and 9 were seronegative. The overall prevalence of CD was 4%. All 4 seropositive and 2 out of 9 seronegative patients responded to GFD in 3 to 6 weeks. Conclusion: Routine endoscopic distal duodenal biopsy is useful for the diagnosis of CD in patients with IBS as it could also detect the disease in patients with negative celiac serology.

Is duodenal biopsy appropriate in areas endemic for Helicobacter pylori?

OBJECTIVE:The primary reason for obtaining duodenal biopsy sample is to diagnose celiac disease. Helicobacter pylori (H. pylori) and drug injury are common causes of duodenitis. The aim of this retrospective study was to explore effects of H. pylori and drugs on duodenal mucosa.METHODS:Duodenal biopsy samples of patients who underwent upper gastrointestinal endoscopy (UGIE) between February 2014 and December 2014 were retrospectively examined. Clinical symptoms, referral indications, endoscopic findings, H. pylori status, and drug history were recorded. Duodenal biopsy findings were compared based on presence of H. pylori and drug history.RESULTS:Of 2389 patients who underwent UGIE, 206 had duodenal biopsy. Eight patients (3.9%) were diagnosed with celiac disease. After excluding cases with celiac disease, 76 patients of remaining 198 patients (36.9%) had duodenal histopathological abnormality. H. pylori was found in 95 (47.9%) patients. Drug usage was less common (42%). Of patients who had histopathological duodenitis, 59% were H. pylori-infected. Rate of duodenitis was higher in H. pylori (+) group than in H. pylori (-) group (45% vs 27.1%; odds ratio, 2.4; 95% confidence interval, 1.3–4.4; p=0.005). There was no difference between groups regarding drug use in terms of histopathological duodenitis.CONCLUSION:H. pylori is the major contributor to duodenitis in high prevalence regions. Serological testing may be more appropriate before performing duodenal biopsy in patients with suspected celiac disease.

OC-028 Does Duodenal Histology Yield any Other Diagnoses for Iron Deficiency Anaemia Apart From Coeliac Disease?: Abstract OC-028 Table 1

Introduction The prevalence of iron deficiency anaemia (IDA) is 2–5% in the developed world. The BSG IDA guidelines recommend screening for coeliac disease (CD) with serology, and those tested positive should undergo duodenal biopsy to assess for villous atrophy (VA). The availability of pre-endoscopy serology in IDA has been shown to be 30%, thus often committing clinicians to routinely biopsy the duodenum. We aimed to explore whether any causes other than CD would be found on duodenal biopsy in IDA. We also aimed to evaluate the role of Simtomax, an IgA/G-deamidated gliadin peptide based point of care test (POCT), in detecting CD in IDA in the endoscopy setting. Methods Group 1: we retrospectively reviewed the duodenal histology of 153 patients with IDA attending a non coeliac specialised IDA clinic in 2013–14. Group 2: we prospectively recruited 133 patients with iron deficiency attending for a gastroscopy to our research gastroscopy list. All patients undertook Simtomax, endomysial antibodies (EMA), tissue transglutaminase (TTG), total IgA, and 5 duodenal biopsies. The results were compared against histology. Results The duodenal histology in group 1 yielded no cause for the IDA apart from CD. Two patients had VA- 1 with positive serology and hence was diagnosed with CD; the other patient never had a serology to confirm the diagnosis as he subsequently died from colon cancer. Assuming the latter case to be CD, the prevalence of CD in this cohort would be 1.3%. 5/7 patients with lymphocytic duodenosis (LD) had a cause for or association with LD: vitiligo, autoimmune hypothyroidism, aspirin use, proton pump inhibitor use, and Helicobacter pylori infection respectively. No attributable causes for LD were found in the remaining 2 patients. In group 2, the prevalence of CD was 19.5%. The sensitivity and NPV of Simtomax were 100%. Conclusion Our duodenal histology review revealed no alternative causes for the IDA other than villous atrophy secondary to CD. Simtomax had 100% sensitivity and NPV for detecting CD in IDA. This suggests that performing a duodenal biopsy in patients with a negative Simtomax test is highly unlikely to yield a diagnosis for IDA, thus could be safely avoided if the sole purpose of the biopsy is to investigate IDA. Simtomax could provide significant cost savings by targeting patients with IDA who require a duodenal biopsy. 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, S. Cross: None Declared, J. Hebden: 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.

PTH-252 Investigation of iron deficiency anaemia. duodenal biopsies – are they worth it?

<h3>Introduction</h3> The prevalence of iron deficiency anaemia (IDA) in adult men and postmenopausal women in the developed world is 2–5%.¹British Society of Gastroenterology (BSG) IDA Guidelines recommend tissue transglutaminase (tTG) antibody as a screening test for coeliac disease. Indications for duodenal biopsies include patients with diarrhoea, weight loss and positive tTG serology. Where coeliac serology is positive, duodenal bulb and D2 biopsies should be taken.²BSG IDA Guidelines do not recommend duodenal biopsy for tTG negative, asymptomatic patients.³However a separate BSG guideline for diagnosis of coeliac disease recommends duodenal biopsies in IDA patients irrespective of Coeliac serology due to the finding of seronegative coeliac disease.² <h3>Method</h3> This audit was carried out to assess adherence to BSG IDA Guidelines for duodenal biopsies in patients referred for IDA investigation with negative tTG antibodies. The study also set out to establish the positive diagnostic yield where biopsies were taken in the same cohort. Patients referred to Newcastle upon Tyne NHSFT adult IDA service between 2011 and 2014 identified as ttG negative and who underwent endoscopy were included. <h3>Results</h3> Two hundred patients were identified, median age 66 (range 19–91); 126 (63%) female and 74 (37%) Male. 114 (57%) patients had duodenal biopsies taken despite tTG being negative and asymptomatic. 28 (19.7%) patients were symptomatic and duodenal biopsies taken, though only 8 (28%) of these patients had 4 biopsy samples and none were from duodenal bulb. Where biopsies were taken, none confirmed coeliac disease. 5/142 (3.5%) patients biopsied had lymphocytic duodenitis but none of them were subsequently diagnosed or treated as coeliac disease. <h3>Conclusion</h3> Duodenal sampling in tTG negative patients did not yield any additional positive diagnosis of coeliac disease. This confirms the recommendations of BSG IDA guidelines. The results of this audit do not appear to support the recommendations made within the BSG coeliac disease guideline for duodenal biopsy being performed regardless of coeliac serology. However, the fact that only 4.9% of patients who had duodenal biopsies taken had duodenal bulb sampled, may limit this conclusion. More efficient use of local endsoscopy and pathology resources can occur by appropriate selection of patients on whom to perform duodenal biopsies. <h3>Disclosure of interest</h3> None Declared. <h3>References</h3> Guralnik JM, Eisenstaedt RS, Ferrucci L, <i>et al</i>. Prevalence of anemia in persons 65 years and older in the United States: evidence for a high rate of unexplained anaemia. Blood 2004;<b>104</b>:2263e8 Diagnosis and management of adult coeliac disease: Guidelines from British Society of Gastroenterology June10, 2014(10.1136/gutjnl-2013-306578) BSG Guidelines for the management of Iron deficiency anaemia May 2011

Are alterations of tight junctions at molecular and ultrastructural level different in duodenal biopsies of patients with celiac disease and Crohn's disease?

Abnormalities of transmembrane and cytoplasmic proteins of tight junctions (TJ) have been implicated in pathogenesis of both celiac (CeD) and Crohn's diseases (CD). Since disease pathogenesis in CeD and CD are different, we planned to study if there is any differential expression pattern of TJ marker proteins and ultrastructural changes, respectively, in duodenal villi vs crypts. Endoscopic duodenal biopsies from treatment naïve patients with CeD (n = 24), active CD (n = 28), and functional dyspepsia (as controls, n = 15), both at baseline and 6 months after treatment, were subjected to light microscopic analysis (modified Marsh grading); immune-histochemical staining and Western blot analysis to see the expression of key TJ proteins [trans-membrane proteins (claudin-2, claudin-3, claudin-4, occludin, and JAM) and cytoplasmic protein (ZO-1)]. Transmission electron microscopy and image analysis of the TJs were also performed. There was significant overexpression of claudin-2 (pore-forming) and occludin (protein maintaining cell polarity) with under-expression of claudin-3 and claudin-4 (pore-sealing proteins) in treatment naïve CeD and active CD with simultaneous alteration in ultrastructure of TJs such as loss of penta-laminar structure and TJ dilatation. Normalization of some of these TJ proteins was noted 6 months after treatment. These changes were not disease specific and were not different in duodenal villi and crypts. Overexpression of pore-forming and under-expression of pore-sealing TJ proteins lead to dilatation of TJ. These changes are neither disease specific nor site specific and the end result of mucosal inflammation.

OC.12.4 INNATE LYMPHOID CELLS ARE INCREASED IN CELIAC DISEASE INTESTINAL MUCOSA AND HAVE A PATHOGENIC ROLE IN A MOUSE MODEL OF SMALL INTESTINE ATROPHY

Background and aim: Innate lymphoid cells (ILCs) are an emerging family of innate hematopoietic cells producing inflammatory cytokines and involved in the pathogenesis of several immune-mediated diseases. The aim of our study was to characterize the tissue distribution of ILCs in celiac disease (CD) and analyze their role in gut tissue damage. Materials and methods: ILC subpopulations were analyzed in lamina propria mononuclear cells (LPMCs), isolated from duodenal biopsies of patients with active CD, patients with inactive CD on a gluten-free diet and healthy controls (HC) and jejunal specimens of patients undergoing gastro-intestinal bypass by flow cytometry. Cytokines, transcription factors and receptors for interleukin (IL)-15, interferon (IFN)-alpha and Toll-like receptors (TLR) were assessed in ILCs either freshly isolated or following incubation of control LPMC with IL-15, IFNalpha and poly I:C, a TLR agonist, by flow cytometry. The role of ILCs in gut tissue damage was evaluated in a mouse model of poly I:C-driven small intestine atrophy. Results: The percentage of total ILCs did not differ between CD (both active and inactive) patients and HC. However, the fractions of ILCs type 1 expressing T-bet and ILCs type 3 expressing ROR-(g)t were significantly increased in active CD compared to controls, while there was no difference in term of ILCs type 2 among groups. ILCs expressed TLR3, IL-15R, little TLR2 but not IFN-alphaR and TLR4. IL-15 and poly I:C, but not IFN-alpha increased IFNgamma expression in ILCs. In vivo in mice, depletion of ILCs significantly reduced TLR3driven small intestinal damage. Conclusions: Active CD is characterized by preferential accumulation of type 1 and type 3 ILC subpopulations and these cells respond to IL-15, a cytokine over-produced in CD, by enhancing IFN-gamma production. The demonstration that ILCs express TLR3, are functionally able to respond to poly I:C with increased synthesis of inflammatory cytokines, and contribute to TLR3-driven small intestinal atrophy delineates a novel mechanism underlying the CD-associated tissue damage.

PTU-185 What is the Cost of Duodenal Biopsies in Patients without Serological Evidence of Coeliac Disease?

IntroductionThe BSG guidelines recommend anti tissue transglutaminase antibody (TTG) testing as a first line test for coeliac disease. Duodenal biopsies (D2) should be performed only after a positive serological test...

Anti-Actin IgA Antibodies Identify Celiac Disease Patients with a Marsh 3 Intestinal Damage among Subjects with Moderate Anti-TG2 Levels

A new diagnostic tool (algorithm-1) for coeliac disease (CD) permitting the diagnosis without performing the duodenal biopsy has been recently proposed by the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN). It combines symptoms associated with CD, high anti-transglutaminase type 2 antibody (anti-TG2) levels, anti-endomysium-IgA antibodies (EMA), and at-risk HLA. Our aims were (i) to evaluate retrospectively in 227 individuals (149 CD patients and 78 controls) the algorithm-1, (ii) to reduce the number of duodenal biopsies among CD patients for whom algorithm-1 is not applicable through the addition of antiactin IgA antibodies (AAA-IgA), and (iii) to evaluate prospectively algorithm-1 and AAA-IgA in 50 patients with suspected CD. Algorithm-1 identified 70 out of 149 CD patients with Marsh 3 lesions. Adding AAA-IgA to the remaining patients with anti-TG2 levels comprised between 4 and 10 times upper limit of normal (ULN) allowed the detection of further 20 patients with a Marsh 3 damage. In our prospective study, algorithm-1 identified 23 out of 50 patients, whilst further 7 were recognized adding AAA-IgA. We confirm that algorithm-1 may avoid the duodenal biopsy in many CD patients and underscores the usefulness of AAA-IgA in reducing the number of duodenal biopsies in patients with moderate anti-TG2 levels.

PWE-116 Can the new ESPGHAN diagnostic guidelines for coeliac disease be applied to adults?

IntroductionIn adults, duodenal biopsy is mandatory for diagnosis of coeliac disease. This is usually preceded by serological tests for coeliac specific antibodies—anti-tissue transglutaminase (tTG) and endomysial antibodies (EMA). However, the...