Tissue Transglutaminase Antibodies Research Articles

Management of coeliac disease patients after the confirmation of diagnosis in Central Europe.

Recently published paediatric guidelines for diagnosing coeliac disease do not include recommendations on the follow-up of coeliac disease patients. The aim of this study was to assess the management practices and experience of coeliac disease patients with their follow-up appointments in Central Europe. Gastroenterologists and coeliac disease patients in five Central European countries were asked to complete the web-based questionnaire focusing on coeliac disease management practices. Answers from 147 gastroenterologists and 2041 coeliac disease patients were available for the analysis. More than half of the gastroenterologists (58.5%) schedule the first follow-up visit within 3 months after the diagnosis. At follow-up, tissue transglutaminase antibodies are checked in almost all patients (95.9%). Approximately two-thirds (60.7%) of gastroenterologists refer all of their patients to the dietitian at diagnosis. Similarly, 42.8% of coeliac disease patients reported that they had not been appointed to a dietitian. Almost one-third of coeliac disease patients (30.8%) reported that they had no follow-up appointments with gastroenterologist at all. Follow-up of coeliac disease patients is suboptimal in Central Europe. Many patients are not followed regularly. A lot of patients are not referred to a dietitian. The recommendations on the optimal follow-up of coeliac disease patients are needed in order to improve patient care.

Juvenil İdiopatik Artrit Hastalarında Çölyak Hastalığı ve Çölyak Dışı Gluten Duyarlılığı Taraması

INTRODUCTION: Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in children characterized by autoimmune etiology. In previous studies, increase In the Incidence of celiac disease (CD) was reported in patients diagnosed with JIA. In this study, the presence of CD and non-celiac gluten sensitivity (NCGS) in patients diagnosed with JIA were investigated. METHODS: Sixty-one (57.3%) JIA patients admitted to the pediatric rheumatology outpatient clinic between January 2020 and April 2020 were included in this cross-sectional study. All patients were evaluated with clinical and laboratory findings in terms of CD and NCGS. Total immunoglobulin (Ig)-A, tissue transglutaminase antibody (tTG) IgA and IgG, anti-endomysium-antibody (EMA) IgA and IgG and anti-gliadin-antibody (AGA) IgA and IgG levels were measured in all patients. RESULTS: Sixty-one JIA patients Including 35 girls, were enrolled in the study. The mean age of the patients was 11.4±4.6 years, the mean age at diagnosis was 10.2±3.4 years. Patients were diagnosed with oligoarticular JIA (n=33), enthesitis-related arthritis (n=18), polyarticular JIA (n=8), and psoriatic arthritis (n=2). All patients were using disease-modifying antirheumatic drugs during the study. Thirty-five patients were receiving biological therapy, concomitantly. The patients (n=2) had abdominal pain, indigestion (n=2), and constipation (n=2). None of the patients had growth retardation. EMA IgA and IgG, tTG IgA and IgG, AGA IgA and IgG tests were negative in all patients. DISCUSSION AND CONCLUSION: CD and NCGS were not detected in our JIA patients. Multicenter studies may guide the clinicians about the circumstances to perform CD and NCGS screening in JIA patients.

Sonographic criteria for the evaluation of dietary compliance of children with celiac disease

Aim: Although the only known way to avoid complications like iron deficiency anemia, short stature in celiac disease is a strict gluten-free diet, it is a known fact that not all patients follow the diet. Diet compliance is practically evaluated with serum antibodies, such as tissue transglutaminase antibody. The aim of this study was to evaluate the contribution of less invasive ultrasound and Doppler ultrasound in evaluating dietary compliance in celiac patients.Materials and Methods: Twenty-five male and 47 female cases aged five to 17 years were included in the study. Seventy-two patients diagnosed with celiac disease and followed up were divided into two groups according to dietary compliance based on the results of tissue transglutaminase IgA antibody. Pericardial fluid, hepatosteatosis, mesenteric lymphadenopathy, intraabdominal free fluid, small intestine diameter, small intestine wall thickness and gallbladder volume, superior mesenteric artery (SMA) diameter, portal vein diameter, SMA peak systolic velocity, and portal vein velocity were measured on ultrasound. The differences between the groups were statistically compared.Results: The frequency of mesenteric lymphadenopathy, superior mesenteric artery diameter, SMA peak systolic velocity, and portal vein velocity were increased in children who did not follow the recommended diet. There was no significant difference between the groups in terms of hyperperistalsis, gallbladder volume, and portal vein diameter. Pericardial fluid, fatty liver, small intestine dilatation, and increased intestinal wall thickness were not detected in either group.Conclusion: Ultrasound can play an important role in the follow up of children with celiac disease. It can provide clinicians with an insight into the dietary compliance of these cases.

Retrospective Study of Tissue Transglutaminase Antibody Levels in Celiac Disease-Suspected Patients at Tertiary Care Hospital in Uttarakhand

Introduction: Celiac disease (CD) is a chronic gastrointestinal disorder arising due to gluten sensitivity in susceptible individuals. In India, one person per 100 is suffering from this disease. CD has been reported more in high wheat-consuming areas like northern India. However, the incidence of CD in patients attending tertiary care hospital of Uttarakhand has not yet been reported. Therefore, this study was planned. Materials and Methods: A retrospective study with 603 patients was done at AIIMS Rishikesh in Biochemistry Department. These patients were screened for CD by tissue transglutaminase antibodies (ttgA) levels using enzyme-linked immunosorbent assay method. Percentage of levels of ttgA <4 U/ml (normal value) and >4U/ml in male, female adults, and children was calculated. Chi-square test was applied to compare results. Results: Out of 603 patients, 23 (3.81%) had abnormally raised ttgA levels (>4 U/ml). Percentage (15.18%) of ttgA levels in male children was significantly (P = 0.01) higher than 2.56% in female children. Mean + standard deviation (SD) of normal and abnormal ttgA levels in patients was 1.17 + 0.45 versus 66.81 + 34.80 U/ml, respectively. Mean + SD of abnormal ttgA levels in children and adults was 72.84 + 41.91 versus 32.38 + 24.75 U/ml, respectively. There was a statistically significant difference in abnormal ttgA levels among children and adults with children predominantly being higher (P = 0.0235). Conclusion: This study shows that levels of ttgA suggestive of CD in children are higher as compared to adults and more in males than females attending tertiary care hospital of Uttarakhand.

Investigation of Tissue Transglutaminase Antibody Normalization in Response to Gluten-Free Diet in Children with Celiac Disease

AbstractA very limited amount of data are available regarding the follow-up of celiac disease (CD) treatment in Iran. The aim of this study is to investigate antitissue transglutaminase (atTG) normalization interval and the associated factors in CD patients. This retrospective study included CD patients enrolled in Children's Medical Center, Tehran University of Medical Sciences. The initial atTG titer and histological evaluation (with Marsh grade ≥2) were recorded. The atTG titer was assessed in each follow-up until the time of normalization where children were strictly on gluten-free diet. The age at the time of diagnosis, gender, Marsh grade at the time of diagnosis, other comorbidities, and family history of CD patients were recorded to determine the association of these factors with antibody normalization interval. In total, 71 patients were recruited in the study of which 34 (47.89%) subjects had atTG level below 20 U/mL at the average interval of 31.36 ( ± 2.89) months (95% confidence interval: 25.7–37.02). There was no significant difference between the antibody normalization interval and different age ranges and Marsh grade. Cox regression demonstrated that gender, age ranges, Marsh grade, positive family history of CD, and the presence of comorbidities did not significantly predict longer antibody normalization interval.

Dermatitis herpetiformis Duhring – evaluation of disease severity and tissue transglutaminase levels in 122 patients on dapsone therapy

ABSTRACTThe aim of our study was to characterize the group of patients suffering from dermatitis herpetiformis Duhring (DH) and to make the statistical analysis of monitored parameters. We retrospectively analysed the data of 122 patients with DH (age, gender, the severity of DH, tissue transglutaminase antibodies IgA (IgA-TGA) level and dapsone dose). The mild form of DH was recorded in 69 patients (56.6%), the moderate form in 48 patients (39.3%) and the severe form in 5 patients (4.1%); 118 patients (96.7%) are on dapsone therapy, 3.2% of patients are only on gluten-free diet. The median of average IgA-TGA in the mild form is 6.25 U/ml, in the moderate form 14.45 U/ml and in the severe form 10.33 U/ml. Although the significant relation of the IgA-TGA to the disease severity was not confirmed, there is some trend in the increase of the IgA-TGA level from mild to moderate and severe form of DH.

Celiac disease can be predicted by high levels of tissue transglutaminase antibodies in children and adolescents with type 1 diabetes.

ObjectivesChildren with type 1 diabetes (T1D) are not included in guidelines regarding diagnosis criteria for celiac disease (CD) without a diagnostic biopsy, due to lack of data. We explored whether tissue transglutaminase antibodies (anti‐tTG) that were ≥ 10 times the upper limit of normal (10× ULN) predicted CD in T1D.MethodsData from the Swedish prospective Better Diabetes Diagnosis study was used, and 2035 children and adolescents with T1D diagnosed between 2005–2010 were included. Of these, 32 had been diagnosed with CD before T1D. The children without CD were repeatedly screened for CD using anti‐tTG antibodies of immunoglobulin type A. In addition, their human leukocyte antigen (HLA) were genotyped. All children with positive anti‐tTG were advised to undergo biopsy. Biopsies were performed on 119 children and graded using the Marsh‐Oberhüber classification.ResultsAll of the 60 children with anti‐tTG ≥10x ULN had CD verified by biopsies. The degree of mucosal damage correlated with anti‐tTG levels. Among 2003 screened children, 6.9% had positive anti‐tTG and 5.6% were confirmed CD. The overall CD prevalence, when including the 32 children with CD before T1D, was 7.0% (145/2035). All but one of the children diagnosed with CD had HLA‐DQ2 and/or DQ8.ConclusionsAs all screened children and adolescents with T1D with tissue transglutaminase antibodies above 10 times the positive value 10x ULN had CD, we propose that the guidelines for diagnosing CD in screened children, when biopsies can be omitted, should also apply to children and adolescents with T1D as a noninvasive method.

Prevalence of Inflammatory Bowel Disease and Celiac Disease in Patients with IgA Nephropathy over Time

Introduction: IgA nephropathy (IgAN) has been connected with increased intestinal permeability and subclinical intestinal mucosal inflammation as well as with inflammatory bowel disease (IBD) and celiac disease – nevertheless, the results are controversial. The prevalence of bowel diseases has increased over time in Western populations. Whether similar trend is seen among IgAN patients remains obscure. Our aim was to study the prevalence of IBD and celiac disease in IgAN patients over time. Methods: The study cohort consisted of altogether 629 patients with newly diagnosed IgAN during years 1976–2012. Data on diagnosis of IBD and celiac disease were retrospectively collected from medical records. Further, to detect unrecognized celiac disease, IgA-class tissue transglutaminase antibodies (tTGA) were measured from serum samples taken at the time of kidney biopsy during years 1980–2012 (defined as screen-detected celiac disease autoimmunity). Results: The prevalence of IBD among IgAN patients increased over time from 0 to 4.4%, while the prevalence of clinically diagnosed celiac disease decreased from 2.6 to 0.6%. Moreover, the number of screen-detected tTGA-positive cases decreased from the 1980s to the 21st century (2.8–0.7%). Conclusion: The prevalence of IBD increased over time in IgAN patients, which exceeds the prevalence of 0.6% in Finnish general population. In parallel, the prevalence of celiac disease and screen-detected celiac disease autoimmunity decreased over time. The coexistence of IBD and IgAN is not negligible. Whether this finding is caused by the increase in the prevalence of IBD in the population or shared pathophysiology between IgAN and IBD remains a matter of further studies.

Long-Standing Ulcerative Colitis and Sulphasalazine Treatment Complicated by Adult Celiac Disease

The risk of celiac disease may be increased in patients with inflammatory bowel disease (IBD), however, the precise pathogenetic mechanisms involved remain controversial. In this report, an elderly man with long-standing and extensive ulcerative colitis was treated with daily salazopyrine for over 30 years. His medication was eventually discontinued although endoscopic surveillance studies showed healed colitis with minimal inflammatory change and no dysplasia. He subsequently volunteered as an IBD control in a celiac disease research study. Endomysial and tissue transglutaminase antibodies were unexpectedly positive and a small bowel biopsy showed changes of celiac disease that later responded to a gluten-free diet. Earlier historical duodenal and ileal biopsies had been normal suggesting that changes were new, developing after cessation of the salazopyrine. This unusual presentation “unmasking” celiac disease after cessation of long-standing salazopyrine for colitis raises the potential that the drug may have acted to suppress the inflammatory process in celiac disease and may offer another alternate and inexpensive therapeutic approach.

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

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

S2433 It's Still the Drug's Fault: A Case of Infliximab-Induced Autoimmune Hepatitis

INTRODUCTION: Autoimmune hepatitis (AIH) is an inflammatory disorder of the liver with a wide spectrum of disease presentation, from asymptomatic elevations in liver associated enzymes (LAEs) to acute liver failure. Recently, biologic agents have been thought to induce AIH in some patients. AIH is associated with elevated immunoglobulins and autoantibodies, although approximately twenty percent of patients with features of AIH lack circulating antibodies. We present a case of infliximab induced seronegative AIH responding to budesonide therapy with successful alteration of ulcerative colitis (UC) treatment regimen to vedolizumab. CASE DESCRIPTION/METHODS: A 31-year-old male with a history of UC on infliximab was noted to have a substantial increase in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) to 181 and 75 U/L, respectively. Broad workup to include serum immunoglobulins, smooth muscle antibody, antimitochondrial antibody, liver kidney microsomal antibody, antinuclear antibody, and tissue transglutaminase antibody were unremarkable. Infliximab was discontinued and the patient was started on vedolizumab for management of his UC. Liver biopsy demonstrated interface hepatitis with lymphoplasmacytic infiltrate, consistent with early AIH vs. drug-induced liver injury (DILI). Three months after discontinuation of infliximab, his liver injury continued to worsen, with increase in ALT and AST to 440 and 168 as well as new elevation in alkaline phosphatase to 137. Given the evidence of ongoing hepatic injury and increasing concern for AIH, high dose oral budesonide was initiated and there was rapid improvement in his LAEs. Azathioprine was added and once his LAEs began to normalize, budesonide tapering was initiated. The patient’s LAEs normalized within two months of starting budesonide and his UC symptoms remain well controlled on vedolizumab. DISCUSSION: Definitive diagnosis of true drug-induced AIH is challenging, as there is considerable overlap with drug-induced AIH-like liver injury, although in this case, histologic findings combined with a brisk response to steroids provided adequate evidence. This case also demonstrated the utility of vedolizumab as a safe and effective therapeutic option for patients with severe IBD after IFX-induced AIH.Figure 1.: Liver biopsy demonstrating mild to moderate portal and parenchymal inflammatory activity with focal interface hepatitis.Figure 2.: Higher power view of the same biopsy featuring inflammatory cells, predominantly lymphocytes with scattered plasma cells (arrow), eosinophils, and macrophages.

S2793 Sprue-Like Enteropathy Secondary to Lisinopril Use

INTRODUCTION: Diarrhea is reported as a rare adverse effect of angiotensin-converting enzyme (ACE) inhibitors, but there are few reports of sprue-like enteropathy from its use. In contrast, this has been well described with the angiotensin II receptor blocker (ARB), olmesartan. We describe a case of drug-induced enteropathy secondary to lisinopril. CASE DESCRIPTION/METHODS: A 76-year-old man with hypertension and coronary artery disease presented with one year of diarrhea, abdominal discomfort and a 35-pound unintentional weight loss. His first EGD yielded duodenal biopsies with villous blunting and increased IELs. Tissue transglutaminase antibody (tTg, IgA) was 22 U/mL (negative is <20 U/mL), and the patient was advised to follow a gluten free diet. He did so for 9 months without symptom improvement and so returned to a gluten-rich diet. Despite a gluten-rich diet for 4 months, the patient’s repeat tTg, IgA and deamidated gliadin peptide (DGP) IgA and IgG were negative. In addition, he was negative for HLA-DQ2 and HLA-DQ8 genotypes, making celiac disease unlikely. All immunoglobulin levels were normal. Then on repeat EGD and colonoscopy, duodenal and terminal ileal biopsies showed villous blunting and dense infiltrate of IELs. Biopsies were negative for Congo red and periodic acid-Schiff diastase stains, sent to evaluate for amyloid and Whipple's disease. Video capsule endoscopy identified diffuse small bowel villous flattening, though no erosions, ulcerations or strictures were seen. Stool testing was negative for giardia and fecal calprotectin. Glucose hydrogen breath test was negative. The patient had a normal fasting gastrin level, and his ANA and anti-enterocyte antibody were negative. We then considered lisinopril-induced enteropathy, as the patient had been on lisinopril since symptom onset. After lisinopril was stopped, the patient's symptoms resolved within 3 months. He gained back weight and no longer had abdominal discomfort. Repeat endoscopy is planned, but was postponed during the COVID-19 pandemic. DISCUSSION: It is important to maintain a high degree of suspicion for drug-induced enteropathy. One study from Italy and Germany examined patients on olmesartan, ARBs and ACE inhibitors and found rare instances of ACE inhibitors leading to intestinal malabsorption (Malfertheiner et al. Pharmacoepidemiol Drug Saf. 2018, 581-586). Olmesartan is classically the medication associated with sprue-like enteropathy, and our case highlights that lisinopril should be considered as well.

Prevalence of celiac disease in patients with short stature: A systematic review and meta-analysis.

Short stature is a common extraintestinal manifestation of celiac disease (CeD). We conducted a systematic review and meta-analysis to assess the global prevalence of CeD in patients presenting with short stature. We searched Medline and EMBASE databases for the keywords "celiac disease, coeliac disease, anti-gliadin, tissue transglutaminase antibody, anti-endomysial antibody, short stature and growth retardation." All the studies published from January 1991 to May 2020 were included. Patients without any prior evaluation for short stature were classified as all-cause short stature, while prior evaluated patients, where no cause was found for short stature, were classified as idiopathic short stature. The diagnosis of CeD was based on the European Society for Paediatric Gastroenterology, Hepatology and Nutrition guidelines. A random-effects model was used to pool the data. Seventeen studies screening 3759 patients (1582 with all-cause short stature and 2177 with idiopathic short stature) were included. The pooled seroprevalence of CeD based on positive anti-tissue transglutaminase antibody and anti-endomysial antibody was 11.2% (95% CI 4.0-21.2%; I2 =86%) and 9.7% (95% CI 2.7-20.2%; I2 =95%) for all-cause and idiopathic short stature, respectively. Similarly, pooled prevalence of biopsy-confirmed CeD was 7.4% (95% CI 4.7-10.6%; I2 =76%) and 11.6% (95% CI 4.1-22.2%; I2 =97%), for all-cause and idiopathic short stature, respectively. There was an overall severe risk of selection bias and significant heterogeneity in the pooled results. Approximately one in 14 patients with all-cause short stature and one in nine patients with idiopathic short stature had biopsy-confirmed CeD. Therefore, evaluation for CeD may be prudent in all patients with short stature.

Prevalence of Celiac Disease in Children and Adolescents With Inflammatory Bowel Disease.

IntroductionThe association between inflammatory bowel disease (IBD) - particularly its two main subtypes, ulcerative colitis (UC) and Crohn’s disease (CD) - and celiac disease (CeD) has been attributed to an overlap in the mechanism of immune dysregulation that characterizes these conditions. Owing to the paucity of studies that have explored this condition in pediatric patients, we examined the prevalence of CeD in children with IBD.Materials and methodsThis is a cross-sectional study of children aged two to 18 years with IBD that were diagnosed between 2016 and 2018. Clinical, demographic, laboratory, and endoscopic data were analysed. Serology for CeD measured the immunoglobulin A tissue transglutaminase (IgA-tTG) antibodies, and the diagnosis was confirmed histologically through small bowel biopsies.ResultsThe study included 101 patients with IBD (83.2% with UC and 16.8% with CD). The mean age was 8.7±4.0 years. Males constituted 59.4% of the cohort, and only 3% had perianal disease. Ileocolonic involvement was reported in 64.7% and non-stricturing and non-penetrating behaviour in 76.7% of CD patients. Pancolitis constituted 45.2% of UC patients. Ten patients (9.9%) had positive serology based on IgA-tTG antibodies, three (approximately 3%) had CeD based on biopsy findings, two patients (2%) had CD, and one patient (1%) had UC. Patients with confirmed CeD had a significantly higher frequency of symptoms of gaseous sensation and bloating (P=0.003) and abdominal distension (P=0.04).ConclusionsThe prevalence of CeD in Egyptian children with IBD is higher than previously reported in a number of similar studies. Abdominal bloating and gaseous sensation were identified as associated symptoms.

Anti-tissue transglutaminase titers are associated with endoscopic findings and severity of mucosal damage in children with celiac disease.

We aimed to assess the correlation between clinical findings, serology, endoscopic findings, and histology in children diagnosed with celiac disease. Medical records of children diagnosed with celiac disease (2010-2017) at the Schneider Children's Hospital were reviewed retrospectively. Correlation between serologic measures anti-tissue transglutaminase (anti-tTG)/anti-endomysial antibodies (EMA) and other variables including mucosal damage, endoscopic findings (scalloping of duodenal folds), and clinical findings (abdominal pain, diarrhea, and anemia) was assessed. Out of 686 patients, 432 patients fulfilled the inclusion criteria (females 262, 61%; median age 6.0; interquartile range 4.0-9.0years). Distribution of histopathology findings was Marsh IIIa 4%, Marsh IIIb 25%, and Marsh IIIc 71% with 313 (73%) patients having anti-tTG titer of ≥ 10 times the upper normal limit. Anti-tTG titer (but not EMA) positively correlated with Marsh grades, scalloping of duodenal folds and anemia. Anti-tTG ≥ 10 times the upper normal limit was associated with Marsh IIIc changes with an adjusted odds ratio of 4.5 (95% confidence interval, 1.7-12.1). Diarrhea and abdominal pain were not associated with serologic, endoscopic, or histologic markers of disease severity.Conclusion: Anti-tTG titers correlated with macroscopic and microscopic mucosal damage, with anemia but not with diarrhea or abdominal pain in children with celiac disease. What is Known: • Tissue transglutaminase antibody titers were shown to correlate with the degree of mucosal damage in patients with celiac disease. • There is a limited evidence regarding the association of celiac serologies with endoscopic and clinical measures. What is New: • Higher titers of tissue transglutaminase but not anti-endomysial antibodies are associated with more severe histologic and endoscopic damage and with the presence of anemia. • Symptoms do not correlate with the severity of mucosal damage such as scalloping of duodenal folds and histopathology changes according to Marsh classification or with serologic markers.

Deamidated gliadin peptide and tissue transglutaminase antibodies in children with coeliac disease: A correlation study

Background and study aimsSerological tests for coeliac disease (CD) are important in the clinical diagnosis and monitoring of response to a gluten free diet (GFD). The tests differ in their sensitivity, specificity, and diagnostic accuracy. In this study, tissue transglutaminase (IgA) (tTG-IgA) antibody was compared with the deamidated gliadin peptide (DGP), of both IgG (DGP-IgG) and IgA (DGP-IgA) types, in patients with CD. Patients and methodsThis cross-sectional study was conducted over a period of 2 years, between 2016 and 2018, at King Abdulaziz University Hospital in children 18 years of age or younger with biopsy-proven CD. Patients' sera were tested for DGP-IgA, DGP-IgG, and tTG-IgA antibodies using enzyme-linked immunosorbent assay (ELISA). A Pearson correlation coefficient and Cohen’s kappa coefficient were performed to analyse the serological tests. ResultsThe study included 26 patients with CD, with a median age of 15 years (range, 5–18 years). Seventeen patients (65.4%) were males. The median disease duration was 5 years (range, 3–14 years). Fifteen patients (57.7%) reported good adherence to a GFD. The patients’ serological tests showed a mean ± SD tTG-IgA titer of 149.8 ± 75 u/ml, a mean DGP-IgG titer of 62.5 ± 36.5, and a mean DGP-IgA of 32 ± 23.3 μ/ml.We found a significant correlation between tTG-IgA and DGP-IgG (r = 0.69, P < 0.001), tTG-IgA and DGP-IgA (r = 0.67, P < 0.001), and DGP-IgG and DGP-IgA (r = 0.83, P < 0.001). Cohen’s kappa coefficient (k) showed substantial agreement between tTG-IgA and DGP-IgG (k = 0.71, P < 0.001) and DGP-IgG and DGP-IgA (k = 0.69, P < 0.001), but moderate agreement between tTG-IgA and DGP-IgA (k = 0.45, P = 0.006). ConclusionWe found a good correlation between tTG-IgA and DGP-IgG and tTG-IgA and DGP-IgA, and substantial agreement between tTG-IgA and DGP-IgG, but moderate agreement between tTG-IgA and DGP-IgA. These results indicate that DGP-IgG was comparable to tTG-IgA and may be useful as an alternative to tTG-IgA in the diagnosis and follow-up of patients with CD.

Utility of narrow band imaging in predicting histology in celiac disease.

Narrow band imaging (NBI) with magnification better visualizes the duodenal microsurface and mucosal vascularity. NBI delineates villous atrophy better than conventional white light endoscopy. This study was conducted to evaluate the diagnostic accuracy of narrow band imaging with magnification(NBI-ME) in celiac disease(CD). In this prospective study, consecutive patients of suspected CD and controls were subjected to tissue transglutaminase antibody test and endoscopic evaluation initially with white light followed by NBI-ME, and biopsies were taken from duodenum. Duodenal villous patterns on NBIwere interpreted as normal, blunted distorted, and absent. Severity of villous atrophy was reported according to the modified Marsh criteria. One hundred andtwenty-two patients (mean age of 27.53 ± 13.37years and a male to female ratio of 1:1.26) and 40 controls were studied. The sensitivity and specificity of NBI-ME in predicting villous atrophy were found to be 95.54% and 90%, respectively. The specificity and negative predictive value of NBI-ME in predicting villous atrophy amongst controls was 100% and 97.5%, respectively. Abnormal findings (blunted and absent villous patterns) combined with elevated transglutaminase antibody (> 5-fold) were found to have high accuracy in predicting villous atrophy. NBI with magnification has high sensitivity and specificity in predicting villous atrophy in patients with celiac disease.

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

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

Piezoelectric Immunosensor for Tissue Transglutaminase Antibodies Determination for Celiac Disease Diagnostic and Comparison with ELISA Method

Piezoelectric Immunosensor for Tissue Transglutaminase Antibodies Determination for Celiac Disease Diagnostic and Comparison with ELISA Method

Correlation of TTG IgA Level with Small Intestinal Histopathological Changes for Celiac Disease among Adult Saudi Patients.

Background and objectivesAccording to recent guidelines, a diagnosis of celiac disease (CD) can be made without a biopsy, especially in children. There are no enough studies despite high prevalence and differences in genetic, race, and cultures. Therefore, we examined the correlation between tissue transglutaminase (TTG) and duodenal biopsy changes in our region because we are identical and different from others in culture, environment, and habits, and the correlation is same as that in different regions.MethodsA retrospective cohort study at the Ministry of National Guard Health Affaires (NGHA) health care facilities that are distributed throughout kingdom of Saudi Arabia from April 19, 2015, till March 29, 2018. This study used the BESTCARE system that includes data from all NGHA facilities; data from 513 patients with CD were collected. All patients diagnosed with celiac disease aged 15 years or more, confirmed by improvement on gluten-free diet (GFD), and were not on GFD before endoscopy or serology test or both of them were included in the study, and the TTG IgA level was measured at the same time or within 2–3 months of biopsy date. The exclusion criteria were negative duodenal biopsy, which is less than 2; patients with negative biopsy and negative serology; patients who were on GFD before testing, and any patients known to have immunity diseases or illness causing mucosal changes. The TTG IgA level was measured in IU/ mL and was labeled as negative (<20 IU/mL) and positive (≥ 20 IU/mL) based on the cutoff value. However, Intestinal biopsy findings were identified as Marsh classification groups.ResultsOne hundred thirty-four patients who met the inclusion criteria were included in the study. Median age of our sample was 24 years (16–37 years). Among these, 99 (73.88%) were female patients, whereas male patients were only 35 (26.12%). Histopathologic investigation of intestinal biopsy were Marsh 0 group was 16 cases (11.9%), Marsh 1 group was 8 cases (6%), Marsh 2 group was 4 cases (3%), Marsh 3a group was 32 cases (23.9%), Marsh 3b group was 64 cases (47.8%), and Marsh 3c group was 10 cases (7.5%). The TTG IgA antibody serology groups were <20 IU/mL in 13 cases (9.7%) and ≥20 IU/mL in 121 cases (90.3%). Among all patients with CD who had negative biopsy (Marsh 0 group), 16 (100%) of them had positive TTG IgA antibody. However, among patients with Marsh 1 group biopsy, 5 (62.5%) cases had negative TTG IgA antibody compared with 3 (37.5%) positive cases. Of the four cases (100%) with Marsh 2 group, all of them had positive TTG IgA antibody. However, in Marsh 3a group biopsy, 3 (9.4%) cases had negative TTG IgA antibody compared with 29 (90.6%) cases with positive TTG IgA antibody. Furthermore, among the patients with Marsh 3b group biopsy, 5 (7.8%) had negative antibody and 59 (92.2%) had positive serology. Of all biopsies of Marsh 3c group, 10 (100 %) had positive TTG IgA antibody.ConclusionsIn perspective of high prevalence of CD in KSA, even more than western countries, we can pretend that positive TTG antibody tests can be applied for the diagnosis of CD without biopsy, particularly in symptomatic patients along with high titer, that is, 5–10 times the upper limit of normal (ULN). However, to validate it further, we need larger prospective studies in which duodenal biopsies should be taken according to recommended protocol and should be interpreted by experienced pathologist. Furthermore, biopsy is still needed in patients who do not show clinical improvement on a gluten-free diet and in cases with mildly or moderately elevated TTG IgA.