Negative tTG 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.

A223 UNMASKED OR INDUCED COLITIS: COULD IT BE SECUKINUMAB?

Abstract Background Spondyloarthropathies (SpA), such as Ankylosing Spondylitis (AS) are inflammatory disorders which have coheritability with inflammatory bowel disease (IBD). Secukinumab is a monoclonal antibody inhibitor of IL-17A used to treat SpA, but has also been reported to cause de novo and exacerbations of known IBD. Rare reports of Secukinumab induced microscopic colitis have also been documented. Purpose To present and discuss the diagnostic challenges in a case of undifferentiated colitis in a patient with AS treated with Secukinumab. Method Case report and literature review. Result(s) Case Report: A 62-year-old male with a history of AS was admitted to hospital with acute on chronic diarrhea. The patient’s AS was unresponsive to Infliximab, Methotrexate, and Adalimumab, although the latter improved his diarrhea at the time. A Colonoscopy completed 14 years earlier for chronic diarrhea was endoscopically normal with biopsies of the left colon notable for mild patchy inflammation and fibrosis. A subsequent Colonoscopy with random biopsies 8 years later showed normal mucosa while he was treated with Adalimumab. He was started on Secukinumab 4 months prior to hospitalization noting progressive watery diarrhea and weight loss of 15kg. Investigations were notable for microcytic anemia (Hemoglobin 120 g/L, MCV 78 fL), elevated CRP (33 mg/L), and a creatinine of 508 µmol/L. Negative tTg antibodies and normal IgA levels ruled out celiac disease. Stool studies were unremarkable. Colonoscopy showed several linear ulcerations in the descending colon and rectum with a normal terminal ileum, transverse, and ascending colon. Biopsies from the endoscopically normal mucosa showed thickened subepithelial collagen band suggestive of microscopic colitis while the ulcerated regions showed cryptic rupture with associated granuloma representing possible Crohn’s colitis versus drug-induced injury. Stains were negative for CMV. Secukinumab was stopped and he was started on Budesonide with significant improvement in symptoms. Literature Review Almost half of all patients with SpA have microscopic intestinal inflammation and of these, 7% eventually develop IBD. Shorter symptom duration, higher SpA activity and male sex are known risk factors for underlying intestinal involvement. However, the exact role of microscopic intestinal inflammation in SpA has yet to be determined. Secukinumab is an inhibitor of IL-17A with significant efficacy in the treatment of SpA but has been associated with exacerbations of Crohn’s disease and de novo cases of IBD. Thus, the role of IL-17 in IBD remains uncertain and may suggest a protective effect rather than an inflammatory one seen in SpA. The long half-life of Secukinumab (24-31 days) presents challenges when considering treatment with other biologics, such as anti-TNFs, which may cause excessive immunosuppression. Image Conclusion(s) New onset colitis is a described but rare entity in patients treated with Secukinumab presenting several diagnostic and treatment challenges. Please acknowledge all funding agencies by checking the applicable boxes below None Disclosure of Interest None Declared

Screening for Celiac Disease in Newly Diagnosed Children with Type I Diabetes

Abstract Background Type I diabetes (T1D) is an autoimmune disease caused by the immune-mediated destruction of insulin-producing pancreatic β cells.. Celiac disease is 5-7 percent more common in people with T1D than in the general population. Objectives The aim of this study was to detect the incidence of coeliac disease among newly diagnosed T1D children by assessment of Anti-tissue Transglutaminase Antibody (anti-tTG), IgA. Methods Fifty children with newly diagnosed T1D and another 15 age and sex –matched healthy individuals were subjected to screening for celiac disease by measuring total body IgA and antiTtg(IgA). Results the incidence of positive anti tTG(IgA) Ab among our T1D patients was found to be 12%. Upon comparing children with positive anti tTG(IgA) Ab with those with negative anti tTG(IgA) Ab we found that children with +ve anti tTG(IgA) Ab were significantly shorter than those with -ve anti tTG(IgA) Ab(p &amp;lt; 0.05). Also HbA1c among our diabetic children with +ve anti tTG(IgA) Ab was significantly higher than those with -ve anti tTG(IgA) (p &amp;lt; 0.05). Gastrointestinal manifestations were significantly higher among T1D patients with anti tTG (IgA)+ve than those with anti tTG(IgA)- ve.(p &amp;lt; 0.001). Conclusion Anti tTG(IgA) Ab levels are elevated in children and adolescents with type 1 diabetes compared with healthy controls with incidence rate of about 12%. Anti tTG(IgA) Ab test can be used as screening test for celiac disease among type1 DM.

Celiac Disease in Indian Children and Adolescents with Type 1 Diabetes

To estimate the time trend and prevalence of celiac disease in 208 children with type 1 diabetes by retrospective case review. Tissue transglutaminase (TTG IgA) levels were done within the first six months of diagnosis and annually on follow-up. Celiac disease was diagnosed in 35 (16.8%; 3 before diagnosis, 18 at initial screening and 14 on follow-up). 14 subjects with negative TTG serology at presentation, developed celiac disease after 3.9 (2.9) years (range 1.4 - 12.6 years, 85.7% within 5 years). Celiac disease is common in Indian children and adolescents with type I diabetes, developing in most within five years of diagnosis.

Estimating the Impact of Verification Bias on Celiac Disease Testing.

The goal of this study was to estimate the impact of verification bias on the diagnostic accuracy of immunoglobulin A tissue transglutaminase (IgA tTG) in detecting celiac disease as reported by an authoritative meta-analysis, the 2016 Comparative Effectiveness Review (CER). Verification bias is introduced to diagnostic accuracy studies when screening test results impact the decision to verify disease status. We adjusted the sensitivity and specificity of IgA tTG reported by the 2016 CER with the proportion of IgA tTG positive and negative individuals who are referred for confirmatory small bowel biopsy. We performed a systematic review from January 1, 2007, to July 19, 2017, to determine these referral rates. The systematic review identified 793 articles of which 9 met inclusion criteria (n=36,477). Overall, 3.6% [95% confidence interval (CI): 1.1%-10.9%] of IgA tTG negative and 79.2.2% (95% CI: 65.0%-88.7%) of IgA tTG positive individuals were referred for biopsy. Adjusting for these referral rates the 2016 CER reported sensitivity of IgA tTG dropped from 92.6% (95% CI: 90.2%-94.5%) to 57.1% (95% CI: 35.4%-76.4%) and the specificity increased from 97.6% (95% CI: 96.3%-98.5%) to 99.6% (95% CI: 98.4%-99.9%). The CER may have largely overestimated the sensitivity of IgA tTG due to a failure to account for verification bias. These findings suggest caution in the interpretation of a negative IgA tTG to rule out celiac disease in clinical practice. More broadly, they highlight the impact of verification bias on diagnostic accuracy estimates and suggest that studies at risk for this bias be excluded from systematic reviews.

MON-372 Treatment-Resistant Vitamin D Deficiency: Is It a Vitamin D Binding Protein Issue?

IntroductionVitamin D is present in free and bound forms; the bound form is complexed mainly to vitamin D binding protein (DBP). Vitamin D levels are affected by age, pregnancy, liver disease, obesity, and DBP mutations. We report a patient with treatment-resistant vitamin D deficiency suggestive of a DBP with abnormal vitamin D binding.Clinical CaseA 58-year-old Pakistani male with a history of hypertension, sleep apnea and hypogonadism presented to endocrine clinic with symptoms including fatigue, generalized muscle cramps, and joint pain. Evaluation of common causes of fatigue, such as anemia, thyroid dysfunction and adrenal insufficiency were ruled out with CBC, thyroid hormone levels and ACTH stimulation test results all within normal ranges. A 25-OH vitamin D level was profoundly low (4.2 ng/ml; normal 30-100), and a 1,25-OH vitamin D level was undetectable (<8 pg/ml; normal 18-72), leading to a presumptive diagnosis of severe vitamin D deficiency. However, his calcium, phosphorus, alkaline phosphatase and kidney function were in the normal range. Furthermore, the absence of osteoporosis, fracture history, or kidney stones suggested adequate vitamin D action at target tissues; PTH levels were high-normal to minimally elevated, ranging 70-94 pg/ml (12-88pg/mL). Aggressive supplementation with vitamin D3 at 50,000 IU 3 times a week and 5,000 IU daily failed to normalize 25-OH vitamin D (ranged 4.6-10ng/ml; normal 30-100) and 1,25-OH vitamin D levels remained undetectable. Addition of calcitriol resulted in mild hypercalcemia and was discontinued. Malabsorption did not appear to be a contributing factor, as a negative tTG antibody (with normal IgA) excluded celiac disease. Vitamin D metabolites levels measured with mass spectrometry showed undetectable 25-OH vitamin D levels (D2 <4 ng/ml, D3 <2 ng/ml; total <6ng/ml; normal 20-50) and 1,25-OH vitamin D levels (<8 pg/ml). Urine N-telopeptide, 24-hour urine calcium (177mg; 100-240) and bone-specific alkaline phosphatase were all normal. Repeat testing over more than five years showed similar results. DBP levels of 269 ug/ml [104-477] excluded DBP deficiency.Clinical LessonVitamin D deficiency is increasingly part of routine testing in internal medicine and endocrinology clinics, as is repletion with high-dose vitamin D. However, in rare cases such as this, relying on 25-OH vitamin D levels can be misleading, and supplementation unnecessary or potentially harmful. Thus, treatment decisions should consider the full clinical context and further evaluation performed when warranted. This patient’s labs are suggestive of an abnormality in the DBP, supporting future examination using molecular testing.

Automated Analyzers Are Suited for Diagnosing Celiac Disease Without a Biopsy.

The European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) 2012 guidelines, enabled for the first time, a nonbiopsy approach in the diagnosis of celiac disease (CD). We aimed to prospectively assess 4 tissue-transglutaminase (tTg) IgA assays of 4 random-access analyzers and examine their accuracy in diagnosing CD without a biopsy. We enrolled 186 consecutive children referred to upper endoscopy and intestinal biopsy. One group included 109 patients with positive tTg that was referred for suspected CD. Another group included 77 patients with negative tTg referred because of other indications. All participants had a blood sample taken at the time of endoscopy. Samples were tested with 4 tTg IgA assays on automated analyzers and 1 Elisa kit. All intestinal biopsies were evaluated by a local pathologist, a central pathologist, and a CD expert blinded to each other. CD was diagnosed when full agreement was reached. Analytical performance of the assays included precision with controls and samples, lot to lot variation, and carryover. In our cohort, all tested tTg IgA-automated assays showed sensitivities above 98% and specificities above 99%. ROC analysis demonstrated AUC (area under the curve) >0.99 for all 4 analyzers. The positive-predictive values (PPV) were all >0.99 and negative-predictive values (NPV) were >0.97. The Elisa kit had sensitivity of 95%, specificity of 96%, AUC of 0.96, PPV of 0.98 and NPV of 0.93. CD can be accurately diagnosed without biopsy based on tTg IgA levels at least 10 times the ULN using the 4 high-volume random-access analyzers used in our study.

3227 Can a Gluten-Free Diet Be an Option in Treating Collagenous Colitis in the Absence of Celiac Disease?

INTRODUCTION: Collagenous colitis (CC), a subtype of Microscopic Colitis, is known to cause chronic diarrhea in the elderly. Steroid medication, particularly budesonide, has been rigorously studied and shown to be effective, leading to remission. Few studies have revealed the role diet has on decreasing these symptoms. CASE DESCRIPTION/METHODS: 69 y/o male with past medical history of chronic intermittent diarrhea for the past thirteen years. He initially presented with recurrence of non-bloody watery diarrhea, alternating with constipation and fecal incontinence for 2 weeks. Previous colonoscopy performed thirteen years ago revealed normal mucosa with diverticulosis. Further workup revealed a negative tTG- IgA, polypharmacy, or an infectious etiology. Labs were unremarkable. He underwent repeat colonoscopy, which demonstrated a fractured and nodular appearance of the cecum and ascending colon with small tears. Biopsies showed a focal increase in intraepithelial lymphocytes with a positive trichrome stain consistent with the diagnosis of CC. He was started on a GFD trial and had complete remission of his symptoms for three years. DISCUSSION: Chronic diarrhea affects approximately 5% of the population and at times can be challenging for gastroenterologists. When working up chronic diarrhea, microscopic colitis and celiac disease often play a large role. In this case, the patient was diagnosed with CC, however symptoms resolved on a GFD alone despite having multiple negative TTG levels. We believe that the multiple negative TTG levels were indicative of negative celiac disease. However, there is evidence showing that gluten can induce microscopic colitis. However, in women dietary gluten intake may not be a risk factor for the development of microscopic colitis in the absence of celiac disease. Nevertheless, the effects of gluten may be different in male veterans. CC is usually treated with a steroid based regimen, budesonide, to obtain remission. There are limited studies that have evaluated the impact that a GFD has upon the symptoms and histological findings in CC. Use of these medications can be associated with hyperglycemia, hypertension and metabolic bone disease which may be detrimental to the patient's health and prognosis. In conclusion, in patients diagnosed with CC consider starting a trial of GFD. Further studies are needed to evaluate the response of how a GFD affects the spectrum of severity in symptoms and histologic findings in patients diagnosed with CC, specifically in male veterans.

Vitamin D level in patients with type 1 diabetes and its relation to tissue transglutaminase immunoglobulin A antibodies

EnIntroductionType 1 diabetes mellitus (T1DM) is a lifelong metabolic disorder, which accounts for ∼10% of all cases of diabetes. Vitamin D deficiency is extensively studied in the pathogenesis of T1DM. Vitamin D regulates both innate and adaptive immunity, and this indicates its potential role in preventing and treating T1DM. T1DM is also associated with celiac disease which is an autoimmune-mediated, chronic inflammatory disorder of the small intestine. Vitamin D deficiency has been described in patients with celiac disease and T1DM.AimThe study’s primary aim was to investigate the 25-hydroxyvitamin D [25(OH)D] level in patients with T1DM and relation between vitamin D level and the presence or absence of tissue transglutaminase immunoglobulin A [tTG (IgA)] antibodies.Patients and methodsThe study estimated 25(OH)D level in 75 patients with T1DM and 15 healthy participants. It also studied the relation between vitamin D level and the presence or absence of tTG (IgA) antibodies.ResultsPatients with T1DM had significantly lower level of 25(OH)D (82.7%) compared with control participants (46.7%) (P=0.003). In all, 5.3% of patients were positive for tTG (IgA) antibody, and antibody titer was significant higher in patients with T1DM, with mean of 1.57±3.38, compared with control participants, with mean of 0.31±0.07 (P=0.001). Vitamin D level was low in diabetic patients with positive tTG (IgA) antibody than diabetic patients with negative tTG (IgA) antibody, but this change did not achieve significant value.ConclusionVitamin D deficiency is high in children and adolescents with T1DM. Its level was decreased in diabetic patients with positive tTG (IgA) antibody than diabetic patients with negative tTG (IgA) antibody.

THE USEFULNESS OF DEAMIDATED GLIADIN PEPTIDE IN SCREENING PEDIATRIC PATIENTS FOR CELIAC DISEASE

Abstract BACKGROUND Celiac disease (CD) is an autoimmune enteropathy triggered by gliadin. The gold standard for diagnosis is small bowel biopsy. Screening with serologic markers to identify endoscopic candidates is commonly completed by paediatricians. The most common serologic marker used for screening is IgA anti-Tissue Transglutaminase (TTG) antibodies. Antibodies to deamidated gliadin peptide (DGP) is a newer assay with studies demonstrating a diagnostic performance similar to anti-TTG. In Canada, this assay has been added to many laboratory’s celiac screening panels. There is little evidence however regarding the usefulness of an isolated positive anti-DGP result in paediatric patients and no study has systematically assessed the presence of biopsy proven CD in solely anti-DGP positive paediatric patients. OBJECTIVES We sought to determine the positive predictive value of anti-DGP for biopsy proven CD in paediatric patients with negative TTG IgA testing. DESIGN/METHODS A multi-center retrospective review of children referred to three centers in Ontario, Canada between January 2015 and December 2016 who had isolated anti-IgG DGP positive CD serology was completed. To be included, patients required serology positive for DGP IgG and negative for all other celiac serologic tests, as well as a duodenal biopsy while on a gluten-containing diet. The positive predictive value of isolated anti-DGP was calculated. RESULTS A total of 83 patients were identified with anti-DGP positive, anti-TTG negative serology. Of these, 40 patients underwent endoscopy. Only 1 patient had findings consistent with CD on biopsy (Marsh 3B histology), yielding a positive predictive value of 2.5%. This patient was IgA deficient. Amongst the cohort of IgA sufficient patients (N=25), the positive predictive value of anti-DGP serology was 0%. One additional patient who was IgA sufficient had findings in keeping with Marsh 2 histology, but repeat TTG and DGP testing was negative. Five patients were found to be IgA deficient at the time of serologic testing, 25 were IgA sufficient and 10 did not have a measured IgA. CONCLUSION Isolated positive DGP IgG serology has a poor positive predictive value for CD, especially in IgA sufficient individuals. For this reason, DGP IgG testing should not be completed as part of the initial screening for celiac disease in the paediatric population unless a compelling reason, such as IgA deficiency or age under 2 years, is present, in order to prevent unnecessary invasive follow-up testing and costs to patients and the health care system.

Adherence to a Gluten-free Diet: Assessment by Dietician Interview and Serology.

We aimed to determine whether tissue transglutaminase (tTG) autoantibody positivity was associated with dietitian-assessed adherence to a gluten-free diet in pediatric patients with celiac disease and identify areas where adherence falters. We reviewed the records of children with celiac disease who had a standardized evaluation of adherence by a registered dietitian. A negative tTG value was not associated with good adherence (P = NS). Adherent and nonadherent children differed with respect to purposeful and accidental gluten exposure (P < 0.0001), knowledge (P = 0.003), cross-contact (P = 0.003), potential exposure via medications and cosmetics (P = 0.004), and potential exposure while at restaurants (P < 0.0001), but not with respect to potential exposure at school (P = NS). Based on our findings, we suggest that negative tTG levels are not necessarily indicative of good adherence to a gluten-free diet in pediatric patients with celiac disease. A separate assessment of adherence is needed focusing on knowledge, behavior while dining out, and intent to adhere.

Undetectable negative tissue transglutaminase IgA antibodies predict mucosal healing in treated coeliac disease patients

Tissue transglutaminase (tTG) immunoglobulin A (IgA) testing is a sensitive adjunct to the diagnosis of coeliac disease. The threshold for positivity was developed for diagnosis, with negative results reported as below the reference value (<4U/mL). To investigate if an undetectable (tTG IgA<1.2U/mL) is more predictive of healing compared to patients with negative but detectable serology (1.2-3.9U/mL). We performed a retrospective study of 402 treated coeliac disease patients seen at the Mayo Clinic with negative tTG IgA values drawn within 1month of duodenal biopsy between January 2009 and December 2015. The Corazza-Villanacci score was used to assess mucosal healing. The presence of gastrointestinal symptoms was also collected. Logistic regression was used to assess the relationship of clinical variables with a normal biopsy. Patients with undetectable titres more frequently had normal duodenal histology compared to patients with detectable tTG IgA levels (117/240 vs. 53/162; OR=1.96; 1.292, 2.961). Asymptomatic patients more frequently had normal duodenum as compared to symptomatic patients (88/163 vs. 82/239; OR=2.25; CI: 1.494, 3.377). Patients with undetectable serology and on a gluten-free diet for ≥2years were more likely to have no villous atrophy compared to patients with detectable serology (148/192 vs. 55/88; OR=2.02; CI: 1.17, 3.49). In subjects recovering from coeliac disease with negative tTG IgA serology, an undetectable titre is associated with normal histology on follow-up biopsy.

Lack of Utility of Anti-tTG IgG to Diagnose Celiac Disease When Anti-tTG IgA Is Negative.

Guidelines for diagnosing celiac disease (CD) recommend initial testing with a highly sensitive serologic test for anti-tissue transglutaminase immunoglobulin A antibodies (tTG IgA). When the probability of CD is high, IgA deficiency should be considered. The 2 approaches to address this include measuring "both tTG IgA and tTG IgG" or measuring "total IgA." We aim to assess the utility of an isolated positive tTG IgG result in diagnosing CD. We conducted a retrospective review of patients undergoing serologic testing for CD from January 1997 to June 2014. Patients with positive tTG IgG and negative tTG IgA were included. Moreover, all patients who had any other positive CD-specific serologic findings were excluded. Demographics, clinical presentation, tests, and biopsy results were recorded. The indication for checking celiac serology was gastrointestinal symptoms in 172 of 233 patients, iron deficiency anemia in 12, and high-risk screening in 48. Small bowel biopsy was performed in 178 patients (77%); 160 had normal results and 18 had histologic changes suggestive of enteropathy. Nine patients had increased intraepithelial lymphocytes, and 9 had partial villous atrophy. Only 6 cases of CD were, however, confirmed. The utility of isolated tTG IgG in diagnosis of CD was low at 3% (6/178). In this cohort of patients, the utility of isolated tTG IgG in diagnosing CD was low at 3%.

Elevated tissue transglutaminase antibodies in juvenile idiopathic arthritis children: Relation to neutrophil-to-lymphocyte ratio and disease activity

Background: Subclinical gut inflammation is described in juvenile idiopathic arthritis (JIA), so has joint involvement been related to celiac disease (CD). The well-known involvement of tissue transglutaminase (tTG) in the pathogenesis of CD stimulated progress in the field of autoimmune diseases. Aim of the work: To screen JIA children for tTG antibodies and to detect its relation to the neutrophil-lymphocyte ratio (NLR) and disease activity. Patients and methods: The study included 44 JIA children with 44 matched controls. All subjects had no GIT symptoms suggestive of CD. Disease activity was assessed using the juvenile arthritis disease activity score in 27 joints (JADAS-27). The tTG antibodies (IgA and IgG) were assessed. Results: The patients mean age was 12.5±2.8years and disease duration 5.01±2.9years; Female:Male 3.4:1. The mean JADAS-27 score was 12.6±2.04. tTG antibodies were positive in 43.2% of the patients compared to 18.2% control (p=0.01). Antibodies positivity was comparable according to gender and subtypes. The NLR in JIA children (1.62±0.58) was significantly higher than in control (1.3±0.5) (p=0.006). Those with positive tTG antibodies had a significantly reduced body mass index (p=0.02) and increased NLR (p=0.02) compared to those with negative tTG. Only NLR and JADAS-27 would significantly predict antibodies positivity (p=0.037 and p=0.04, respectively). Conclusion: Increased tTG antibodies are frequent in JIA children raising the possibility of an associated subclinical CD. Markedly reduced BMI and increased NLR could forecast the presence of these antibodies. In addition to the JADAS-27, the NLR is a simple test that could predict this association and could be a useful biomarker.

The Usefulness of IgA/IgG DGP/tTG Screen Assay for Celiac Disease Detection among Symptomatic and at Risk Young Children

Background: It has been postulated that IgA anti tissue-transglutaminase (tTG) and anti-endomisium (EMA) antibodies can be false negative in young children.ESPGHAN recommended for seronegative children younger than 2 years old with clinical suspicion of celiac disease to perform duodenal biopsies. Recent studies sugested that the combined assay for IgA/IgG deamidated gliadin peptides (DGP) and tTG can detect celiac disease among seronegative young children. Aim: To assess if the new combined assay with synthetic gliadin derived peptides IgA/IgG-DGP/tTG is useful to detect celiac disease in IgA tTG or EMA seronegative children younger than 2 years old. Methods: The authors screened a lot of children aged 6 months to 2 years old that associated characteristic symptoms/risk factors for gluten enteropathy. 368 children were tested for IgAtTG, EMA and IgA/IgG-tTG/DGP combined assay. All children had normal total IgA concentration and were consuming gluten at the time of enrolment. Children with at least one positive serologic test underwent intestinal biopsy, including seronegative infants, DQ2/DQ8 positive, with clinical suspicion of celiac disease that underwent the 2 biopsies protocol. Results: Celiac disease was diagnosed in 22 children based on histology. 19 children were positive for IgA tTG, 20 were positive for EMA and 21 tested positive for IgA/IgG-DGP/tTG. IgA tTG sensitivity was 86.3%, IgA EMA sensitivity was 91% and IgA/IgG-DGP/tTG sensitivity was 95.4% (p=0.002). Conclusions: The sensitivity of IgA/IgG DGP/tTG assay was significantly higher than that of IgAtTG in celiac patients younger than 2 years old.The better performance of this new combined test can avoid repeated intestinal biopsies in young children with high clinical suspicion of celiac disease but negative tTG/ EMA serology.

The Benefit of Separate Bulb Biopsy in Children Undergoing an Esophagogastroduodenoscopy

Background: Esophagogastroduodenoscopy (EGD) is an essential diagnostic test in children with gastrointestinal diseases. Small bowel biopsies (SBB) are usually collected from the distal duodenum. A duodenal bulb biopsy (DBB) is recommended in children with celiac disease (CD), because up to 8% can have exclusive bulb injury. This study aims to assess the benefit of separate bulb biopsy in children who underwent EGD and had DBB performed. Methods: We reviewed the electronic medical records between 011998 and 05-2014. All children who underwent an EGD with separate DBB were included. Demographic, clinical, and histopathological parameters were recorded. Results: A total of 211 children were identified. The average age was 10 years (range 1-17 years). Fifty-eight patients had CD, and 153 were non-CD. All patients with CD had positive celiac serology, whereas in non-CD, 10 had positive serology (5 TTG IgG with negative TTG IgA, 1 TTG IgA, and 4 DGP IgG with normal villous architecture). In patients with CD, DBB was diagnostic in 2 (3%) with exclusive bulb injury and confirmatory in 3 (5%) with partial villous atrophy in the bulb and only increased intraepithelial lymphocytes (IEL) distally. In the non-CD group, 7 (4.5%) patients had exclusive bulb injury (4 peptic duodenitis and 3 IEL). Conclusions: In children with CD, DBB increased the diagnostic yield by 9%. In the non-CD group, isolated bulb injury was found in 4.5%, with unclear clinical significance suggesting that DBB may carry higher specificity to CD.

PTU-159 Comparison of three commercially available point of care tests for coeliac disease: Abstract PTU-159 Table 1

<h3>Introduction</h3> Coeliac disease (CD) remains underdiagnosed. A rapid point of care test (POCT) may increase uptake of serological testing in appropriate patient groups. 3 POCTs are commercially available in the UK and in continental European pharmacy outlets: Biocard an IgA tissue tranglutaminase (tTG) test (BHR pharmaceuticals); Celiac Quick Test (Biohit Healthcare) detecting IgA, IgG and IgM tTG and Simtomax (Tillotts Pharma) which detects IgA and IgG antibodies against deamidated gliadin peptides (DGP). A fourth POCT has also been developed but not marketed (Xeliac Test Pro, Personal Diagnostics), with availability being solely from the manufacturer and no published data existing supporting its validity. Of the 3 commercially available POCTs, there is a limited evidence base with significant ascertainment bias. For this reason we decided to compare 3 commercially available tests in an endoscopic setting. <h3>Method</h3> Patients referred with a positive endomysial antibody (EMA) for duodenal biopsy to confirm CD were recruited. All patients had repeat serum EMA, tTG and immunoglobulins and were tested simultaneously with the 3 POCTs as per the manufacturers’ instructions. All patients had quadrantic duodenal biopsies from the second part of the duodenum as well as a duodenal bulb biopsy. Demonstration of villous atrophy (VA) was required to diagnose CD. <h3>Results</h3> 82 patients (51.2% female, mean age 41.0) have been recruited. In 10 patients the EMA had normalised on repeat testing. None of these patients had VA on duodenal biopsy. 9 of these patients were referred with a weak EMA and had a negative tTG. One patient had a tTG of 10 times the upper limit of normal, and subsequent gluten challenge revealed a positive EMA and VA. Of the remaining 72 patients 59 new cases of CD were confirmed with the presence of villous atrophy, of the 13 EMA positive patients without VA 8 had Marsh 1 or 2 changes present with the remaining 5 patients having normal histology. Full sensitivity, specificity PPV and NPV for all of the tests compared to VA on duodenal biopsy are shown in Table 1. <h3>Conclusion</h3> In this pilot data set Simtomax appears to be the most sensitive of the POCTs when compared to histology with similar results to serum tTG as screening test. Further work is required in larger cohorts and lower prevalence populations to confirm the utility of these tests in adult CD. <h3>Disclosure of interest</h3> P. Mooney: None Declared, S. Wong: None Declared, M. Burden: None Declared, M. Kurien: None Declared, M. Hadjivassiliou: None Declared, D. Sanders Grant/ Research Support from: BHR pharmaceuticals; Tillotts Pharma for investigator led studies.

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

PTU-163 The role of serology testing and duodenal biopsy for the investigation of coeliac disease in patients with unexplained anaemia

Introduction Current guidelines recommend testing for Coeliac Disease in all patients undergoing investigation for anaemia with either serology testing, for tissue transglutimase antibody (TTG) or duodenal (D2) biopsies to confirm histological evidence of intestinal damage. The present study aimed to assess the approach for diagnosing Coeliac Disease by (i) examining current practice and (ii) assessing the efficacy of TTG testing. Method A retrospective audit of all adult patients undergoing upper GI endoscopy at a single centre, between August 2013 and July 2014 (inclusive), was performed. A database was created with demographics including age, sex, socioeconomic deprivation, haemoglobin level (Hb), TTG serology result, D2 biopsy result and findings at endoscopy. Results During the study period, 4,788 patients underwent upper GI endoscopy, of which unexplained anaemia was the indication in 814 (17%). Of these, complete results were available for 789 (97%), which were included for analysis. Mean age 66 years, 440 (56%) female, 296 (38%) socioeconomically deprived. Mean Hb levels were 102 g/L (males) and 97 g/L (females). Of these, 580 (74%) patients underwent investigation for Coeliac Disease (79 TTG serology only; 334 D2 biopsy only; 167 both) of which 14 (2%) patients had histological confirmation of the disease. Of the 209 patients who were not screened for Coeliac Disease, 144 (64%) had an alternative source of bleeding found at time of endoscopy. Patients with confirmed Coeliac Disease were likely to be younger (p = 0.017) than those without. There was no association between sex (p = 0.473), deprivation (p = 0.235) or Hb level (p = 0.856 (males), p = 0.543 (females)) and the risk of Coeliac Disease. Of those undergoing both TTG and D2 biopsy (n = 167), 2 patients had negative TTG serology and positive D2 biopsy and 1 patient had positive TTG and negative D2 biopsy, yielding an estimated sensitivity and specificity of TTG serology testing of 82% and 99% respectively. Conclusion The results of the present study indicate that the majority of patients undergoing endoscopy for investigation of anaemia, in our single centre, are appropriately investigated for Coeliac Disease. However, TTG has reduced sensitivity and within a cohort of patients who will be undergoing endoscopy its role is limited. Disclosure of interest None Declared.

Sa1307 Comparison of Three Commercially Available Point of Care Tests for Celiac Disease

Introduction Coeliac disease (CD) remains underdiagnosed. A rapid point of care test (POCT) may increase uptake of serological testing in appropriate patient groups. 3 POCTs are commercially available in the UK and in continental European pharmacy outlets: Biocard an IgA tissue tranglutaminase (tTG) test (BHR pharmaceuticals); Celiac Quick Test (Biohit Healthcare) detecting IgA, IgG and IgM tTG and Simtomax (Tillotts Pharma) which detects IgA and IgG antibodies against deamidated gliadin peptides (DGP). A fourth POCT has also been developed but not marketed (Xeliac Test Pro, Personal Diagnostics), with availability being solely from the manufacturer and no published data existing supporting its validity. Of the 3 commercially available POCTs, there is a limited evidence base with significant ascertainment bias. For this reason we decided to compare 3 commercially available tests in an endoscopic setting. Method Patients referred with a positive endomysial antibody (EMA) for duodenal biopsy to confirm CD were recruited. All patients had repeat serum EMA, tTG and immunoglobulins and were tested simultaneously with the 3 POCTs as per the manufacturers’ instructions. All patients had quadrantic duodenal biopsies from the second part of the duodenum as well as a duodenal bulb biopsy. Demonstration of villous atrophy (VA) was required to diagnose CD. Results 82 patients (51.2% female, mean age 41.0) have been recruited. In 10 patients the EMA had normalised on repeat testing. None of these patients had VA on duodenal biopsy. 9 of these patients were referred with a weak EMA and had a negative tTG. One patient had a tTG of 10 times the upper limit of normal, and subsequent gluten challenge revealed a positive EMA and VA. Of the remaining 72 patients 59 new cases of CD were confirmed with the presence of villous atrophy, of the 13 EMA positive patients without VA 8 had Marsh 1 or 2 changes present with the remaining 5 patients having normal histology. Full sensitivity, specificity PPV and NPV for all of the tests compared to VA on duodenal biopsy are shown in Table 1. Conclusion In this pilot data set Simtomax appears to be the most sensitive of the POCTs when compared to histology with similar results to serum tTG as screening test. Further work is required in larger cohorts and lower prevalence populations to confirm the utility of these tests in adult CD. Disclosure of interest P. Mooney: None Declared, S. Wong: None Declared, M. Burden: None Declared, M. Kurien: None Declared, M. Hadjivassiliou: None Declared, D. Sanders Grant/ Research Support from: BHR pharmaceuticals; Tillotts Pharma for investigator led studies.