Tissue Transglutaminase Antibody and Its Association with Duodenal Biopsy in Diagnosis of Pediatric Celiac Disease (original) (raw)
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Indian Journal of Clinical Biochemistry, 2017
Traditionally small intestinal biopsy has been considered a gold standard for the diagnosis of celiac disease (CD). But now data has shown that serological markers like anti-tissue-transglutaminase antibodies (tTGA) can be used to make the diagnosis with great sensitivity and specificity. The objective of the present study was to evaluate whether patients with high probability of CD and high titre of tTGA, have a high probability of intestinal damage and may not require biopsy for final diagnosis. All the cases with tTGA levels C15 IU/ml and who subsequently underwent biopsy from July 2010 to June 2013 were selected. Histopathological findings graded as per Marsh classification were correlated with serum tTGA levels. Grade 3 lesions were considered diagnostic for the disease. Out of total 731 patients 470 had serum tTGA levels [100 IU/ml and 261 patients had \100 IU/ ml. Highest levels of tTGA (219.3 IU/ml) were seen in grade 3c which was [12 times the normal cutoff value. Mean serum tTGA in higher histological grade i.e. 3 (3a, 3b, 3c) was 186.7 IU/ml ([12 times the normal cut off value) as compared to grade 1 which was 108.9 IU/ml ([7 times the normal cut off value). Using a tTGA cutoff value of 70 IU/ml, sensitivity was found to be 83.9% while specificity was 56.10% with an overall accuracy of 77.7%. This study confirms that a small intestinal biopsy is not always necessary for the diagnosis of CD in symptomatic patients with high tTGA levels ([70 IU/ml).
Journal of Clinical Laboratory Analysis, 2001
The aims of this study were: (1) to compare the diagnostic efficacy for celiac disease (CD) diagnosis of serum determination of anti-gliadin (AG) (IgA and IgG) and anti-endomysium (AE) with that of anti-transglutaminase (AtTG); and (2) to compare the accuracy of four different assays to measure AtTG. We studied 72 children: the histological diagnosis of CD was made in 38 cases and excluded in the remaining 34 children. In fasting sera we measured AE, AG-IgA and IgG, and AtTG, the latter with four different commercial kits (Eurospital, Medipan, Inova, Arnika). Moreover AtTG was measured in a group of 58 CD children after a gluten-free diet. AE was positive in all but 1 case of CD patients (sensitivity = 97%); false positive results were found in 1/34 controls (specificity = 97%). When a specificity of 95% was fixed, the sensitivities were 97% for AE, 83% for AG-IgA, and 63% for AG-IgG; the sensitivities of anti-tTG were 90, 84, 84, and 75% when measured with Eurospital, Medipan, Inova, and Arnika kits respectively. The new AtTG seems to be accurate enough to be proposed as a noninvasive diagnostic tool for CD diagnosis; the 4 kits analyzed showed similar diagnostic efficacy. J. Clin. Lab. Anal. 15:112–115, 2001. © 2001 Wiley-Liss, Inc.
Retrospective analyses of antibody titers in the diagnosis of pediatric Celiac Disease
Medical Science and Discovery, 2023
Objective: We aimed to evaluate the relationship between Tissue Transglutaminase IgA titer (tTGIgA) and Endomisium antibody (EMA) positivity and the stage of duodenal mucosal damage at Celiac disease (CD). Material and Methods: The study group consisted of 233 children (2-18 years old) who were diagnosed with CD and admitted to our XXX Hospital, Pediatric Gastroenterology Outpatient Clinic, between September 2017 and November 2022. All patients underwent an endoscopy, and a histopathological diagnosis was made. In upper gastrointestinal endoscopy, one biopsy sample were taken from the duodenum bulb and four samples from the second part of the duodenum. Histological patterns were evaluated according to the Marsh-Oberhuber classification. Results: A total 233 patients with CD were included in the study. The mean age of the patients at the time of diagnosis was 97.0 ± 57.1 months. The patients' mean tissue transglutaminase (tTG) IgA value was 172 ± 133. The most common Marsh-Oberhuber classification was found to be Marsh 3b (47.6%) in CD patients. According to the Marsh-Oberhuber classification, the mean tTGIgA values were significantly different compared to the groups. Conclusion: We recommend starting a diet with a diagnosis of CD without endoscopy for patients with a tTGIgA value of 10 X ULN (upper limit of normal) or more recommended by ESPGAN, and we even support randomized prospective studies to reduce this value to 7-10 times or less.
Journal of Clinical Gastroenterology, 2015
Goals: We reviewed our celiac disease (CeD) database to study if anti-tissue transglutaminase (tTG) antibody (ab) titers correlate with severity of villous abnormalities in Indian patients and to find out a cutoff value of anti-tTG ab fold-rise, which could best predict CeD. Background: Guidelines for diagnosing CeD suggest that biopsy could be avoided in some patients with high anti-tTG ab titer. Study: We reviewed a cohort of 366 anti-tTG ab-positive individuals in whom duodenal biopsies were performed. Anti-tTG ab was obtained before initiation of gluten-free diet. Anti-tTG ab results were expressed in terms of fold-rise by calculating ratio of observed values with cutoff value. CeD was diagnosed if in addition to positive serology, patients had villous atrophy (>Marsh grade 2) and unequivocal response to gluten-free diet. Results: The mean anti-tTG fold-rise in groups with Marsh grade r2 was 2.6 (± 2.5), grade 3a was 4.0 (± 3.9), 3b was 5.7 (± 5.1), and 3c was 11.8 (± 8.0). The positive likelihood ratio for diagnosing CeD was 15.4 and 27.4 at 12-and 14-fold-rise of anti-tTG ab titer, respectively. The positive predictive value of diagnosis of CeD was 100% when anti-tTG ab titer was 14-fold higher over the cutoff value. Fifty-seven (43.9%) individuals with anti-tTG titer rise <2-fold high also had CeD. Conclusions: As severity of villous abnormality increases, titer of anti-tTG also rises. Presence of villous atrophy can be predicted at very high anti-tTG ab titer. In contrast to emerging belief, mucosal biopsies should be performed even if anti-tTG ab titer is <2 times, because many patients with CeD have low titers.
TITLE: DIAGNOSTIC UTILITY OF CONVENTIONAL CELIAC DISEASE SPECIFIC MARKERS
Background: Serology based diagnosis of celiac disease (CD) or patient selection for duodenal biopsy remains a dilemma. Objectives:This study was performed to assess the diagnostic accuracy of conventional CD specific serological markers. Patients and Methods: This retrospective study was performed at King Khalid University Hospital, Riyadh Saudi Arabia. Data were extracted from 237 patients investigated for CD between March 2012 and June 2014. Data for histological and serological assessment were available for 61/237 patients (36 females and 25 males; mean age28.3+14 years).CD was confirmed histologically in 37 (60.7%) patients. Results:Frequently detected antibodies were anti-gliadinIgG in 88.5% and anti-tissue transglutaminase IgA (a-Ttg IgA) antibodies in 65.6% patients. The most reliable marker for the diagnosis of CD was a-Ttg IgA with a sensitivity of 97%, specificity of 83%, positive predictive value (PPV) of 90% and a negative predictive value (NPV) of 95%. None of the other CD-specific marker matched the performance of a-Ttg IgA antibody. Performance of the composite marker developed using discriminant analysis surpassed all markers with a sensitivity of 97%, specificity of 92%, PPV of 95% and NPV of 96%. The area under curve for composite marker with 95% confidence interval was 96.7% (92%-100%) significantly higher (p=0.04) than that of a-Ttg 90.3% (82.3%-98.4%). The apparent prevalence of anti-gliadin IgA (62%) was almost similar to true prevalence (61%). Conclusion: For the diagnosis of CD a-Ttg IgA displayed a high level of diagnostic accuracy as an individual marker however the performance of composite marker was significantly higher than a-Ttg IgA.
Clinical and Vaccine Immunology, 2006
A meta-analysis of studies investigating the diagnostic accuracy of enzyme-linked immunosorbent assays (ELISA) for antibodies against tissue transglutaminases (tTG) of various origins in celiac disease (CD) diagnosis was carried out. Twenty-one studies, with untreated CD patients and healthy/CD-free controls, were included in the meta-analysis. The diagnostic accuracy was estimated using a summary receiver operating characteristic (SROC) curve and pooled sensitivity (Se) and specificity (Sp). Multiple assays within a study were treated by considering all the assays within a study and by analyzing the most popular assay (i.e., the commercial anti-tTTG ELISA most frequently utilized in the papers in which multiple assays were included). The SROC curve indicated the absence of heterogeneity, and the superiority of recombinant human tTG (rh-tTG) and purified human tTG (ph-tTG) compared to guinea pig-tTG (gp-tTG). The sensitivities (most popular assay) for rh-tTG, ph-tTG, and gp-tTG were 94%, 90%, and 92%, respectively, and the specificities were 97%, 92%, and 96%, respectively. A sensitivity analysis (exclusion of studies with bias) altered the results of ph-tTG: Se, 95%; Sp, 98%. The sensitivities (all individual assays) for rh-tTG, ph-tTG, and gp-tTG were 94%, 94%, and 91%, respectively, and the specificities were 95%, 94%, and 89%, respectively. Human tTG ELISA is sensitive and specific, and it can be used for mass screening. Sensitivity analysis showed that ph-tTG might perform better.
We measured anti-transglutaminase (anti-tTG) antibody in the culture medium of intestinal biopsy specimens from patients with suspected celiac disease (CD) and evaluated the relationship between antibody production and severity of intestinal mucosal damage. Methods: We performed diagnostic testing for CD on 273 consecutive patients. In addition to routine histologic evaluation of duodenal biopsy specimens, we assayed anti-tTG antibodies in serum and in the culture medium of duodenal biopsy specimens. Results: CD was diagnosed in 191 of the 273 patients. Sensitivity and specificity of the serum anti-endomysium (EmA) and anti-tTG assays were 83% and 85% and 99% and 95%, respectively, and both had 88% diagnostic accuracy. EmA and anti-tTG assayed in the culture medium had 98% sensitivity, 100% specificity, and 98% diagnostic accuracy (vs serum assays; P <0.0001). Twenty-nine CD patient specimens (16%) were negative for serum anti-tTG and EmA; for 24 of these patients, anti-tTG assay of the culture medium was positive. The CD patients whose biopsy specimens were positive for serum antibodies showed the following intestinal histologies: total villous atrophy, 35%; severe villous atrophy, 25%; mild atrophy, 25%; villi with no atrophy but with increased intraepithelial lymphocytes, 15%. None of the CD patients whose specimens were negative for serum antibodies showed total or severe villous atrophy; 77% had mild villous atrophy, and 23% had no villous atrophy but had increased intraepithelial lymphocyte counts. Mild villous atrophy was also seen in specimens from ϳ15% of patients without CD. Conclusion: Anti-tTG assay of the culture medium of biopsy specimens can improve the accuracy of CD diagnosis in patients negative for serum antibodies.
Clinical accuracy of anti-tissue transglutaminase as screening test for celiac disease under 2 years
Acta Paediatrica, 2011
Aim: To investigate, in patients with suspected celiac disease (CD) younger than 2 years, the clinical value of anti-tissue transglutaminase (tTG) in diagnostic work-up of CD. Methods: Between June 2005 and June 2009, 169 patients aged <2 years, with symptoms suggestive of CD, were submitted to biopsy. CD diagnosis was based on the revised criteria of the European Society for Pediatric Gastroenterology, Hepatology and Nutrition.
PEDIATRICS, 2001
Objective. An immunoglobulin A (IgA) anti-tissue transglutaminase antibody assay (anti-tTG) was compared with the conventional IgA anti-endomysium antibody assay (EMA) to assess its reliability as a screening test for celiac disease (CD) in a pediatric population. Methods. Seventy-five IgA-sufficient and 2 IgA-deficient children who were scheduled for small intestinal biopsy for the evaluation of history or symptoms suggesting a diagnosis of CD were prospectively evaluated and enrolled in this study (gastrointestinal [GI] patients). In addition, 16 children with type I diabetes mellitus (DM) who had a positive EMA and a small bowel biopsy were included as a separate cohort. IgA anti-tTG was measured by enzyme-linked immunosorbent assay (ELISA), and IgA-EMA titers were determined by indirect immunofluorescence on cryopreserved sections of monkey esophagus. Results. Nine of the 75 IgA-sufficient GI patients had a small bowel biopsy consistent with the diagnosis of CD. Eight of 9 IgA-sufficient patients with a positive small bowel biopsy had positive anti-tTG and EMA tests. Four IgA-sufficient patients had a false-positive anti-tTG ELISA and 2 had a false-positive IgA-EMA assay. In the IgA-sufficient patients, the sensitivity was 89% and the negative predictive value was 98% for either assay. The specificities of the IgA anti-tTG and the IgA-EMA tests were 94% and 97%, respectively (not significant). The positive predictive value of the IgA anti-tTG was 67%, compared with 80% for the IgA-EMA (not significant). In the 2 IgA-deficient children, one of whom had biopsyproved CD, both tests were negative. In the 16 DM children 12 true-and 4 false-positive IgA anti-tTG and IgA-EMA results were identified. Three of 12 complained of GI symptoms. In follow-up, thus far, none of the DM patients with a false-positive anti-tTG have developed CD. Conclusions. The IgA anti-tTG antibody assay is equivalent to the IgA-EMA assay as a screening test for CD in IgA-sufficient pediatric patients. Intestinal biopsy remains the gold standard for the diagnosis of CD.
Looking for Celiac Disease: Diagnostic Accuracy of Two Rapid Commercial Assays
The American Journal of Gastroenterology, 2006
BACKGROUND: Early diagnosis and treatment with gluten-free diet reduces mortality and the prevalence of associated disorders in celiac disease (CD). A simple "in the office" test of anti-transglutaminase antibodies might be of great help in first-line screening for CD.