Can Tissue Transglutaminase Antibody Titers Replace Small-Bowel Biopsy to Diagnose Celiac Disease in Select Pediatric Populations?

Department of Pediatrics, British Columbia Children's Hospital, University of British Columbia, Vancouver, British Columbia, Canada.
PEDIATRICS (Impact Factor: 5.47). 05/2005; 115(5):1341-6. DOI: 10.1542/peds.2004-1392
Source: PubMed


The use of screening tests for celiac disease has increased the number of patients referred for evaluation. We proposed that the subgroup of patients with very high tissue transglutaminase antibody (TTG) titers is positive for celiac disease and a small-bowel biopsy is not necessary to make the diagnosis. A gluten-free diet should be attempted and, if the patient's symptoms do not improve, then a biopsy should be performed to confirm the diagnosis.
A chart review of data for 103 patients who underwent both TTG testing and a small-bowel biopsy was performed. We examined the impact of using TTG values of >100 U and <20 U as cutoff values and suggested performing biopsies for patients with TTG values of 20 to 100 U, as is current practice.
Fifty-eight of 103 patients demonstrated positive biopsy results. Forty-nine of 103 patients had TTG levels of >100 U, with 48 of 49 exhibiting positive biopsy results. Only 7 of 16 patients with TTG values of 20 to 100 U exhibited positive biopsy results. Three patients with TTG levels of <20 U had positive biopsies; 2 were IgA negative and 1 had a duodenal ulcer. With the cutoff values of >100 U and <20 U with known IgA status, the sensitivity was 0.980 (48 of 49 cases) and the specificity was 0.972 (35 of 36 cases). An incremental cost analysis found that this proposal could potentially decrease the costs of investigation and diagnosis by almost 30%.
When the cutoff values were changed to >100 and <20 U and IgA levels were verified, the sensitivity and specificity were very high. Patients with mid-range TTG values (20-100 U) or values of <20 U with negative IgA status should continue to undergo biopsies for diagnosis of celiac disease.

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    • "Some authors proposed not to perform endoscopy and biopsy on classic symptomatic patients (diarrhea, failure to thrive, malabsorption) with high levels of ATTG (>100 U/l) [6]. Those patients after some months of a gluten-free diet have the resolution of symptoms and normalization of serology [10]. In our experience, when ATTG antibodies were higher than 100 U/l, histology always showed a mucosal atrophy (MARSH 3a-3c), except for one case. "
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    ABSTRACT: Prevalence of celiac disease in developed countries is assessed about 1:100--1:150. The real prevalence is unknown because mass screenings are expensive and difficult to organize. Moreover celiac disease can affect people at every age and studies on asymptomatic subjects at different ages are not comparable. In this study we wanted to know the real prevalence of celiac disease in children in the Republic of San Marino. We also analysed concordance of different tests used and costs of mass screening. The study started in 1993. From 1993 to 1997 children aged 6, 10 and 14 were screened. Since 1997 only children aged 6 were monitored, in order to have a homogeneous population. In fact, every child born since 1980 was taken into account. Children were recruited by classroom lists of students for general paediatric examination. Until 2005 the screening test was based on dosage of antibodies anti-gliadin (AGA) IgA and IgG on venous blood. Since 2006 these tests were replaced by anti-transglutaminase IgA antibodies (ATTG). Anti-endomysial antibodies (EMA) were performed if result of any between either AGA or ATTG tests was positive or borderline; if EMA was positive, then an endoscopy with histological examination was performed to confirm the final diagnosis. Attendance to paediatric examination was 96%, submission to blood test was 87%. 42 on 5092 (0,8%; 1:125) children resulted affected by celiac disease. Histology always confirmed diagnosis by serology except for two cases. AGA test (until 2005) yielded 28 on 4304 (0,7% 1:143); ATTG test (since 2006) revealed 14 positive cases on 788 (1,8%; 1:55) leading to a larger percentage of diagnosis. EMA antibodies always confirmed positivity of ATTG. Prevalence of celiac disease in children of Republic of San Marino is comparable to other North-European Countries. Sensitivity of ATTG proved much higher than that of anti-gliadin antibodies. Concordance between ATTG and EMA was 100%. Concordance between serology and histology was approximately 100%. Cost of screening was yearly about 5000 euros (250 children screened every year).
    Full-text · Article · Oct 2013 · Italian Journal of Pediatrics
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    • "Several recent studies have questioned the necessity of performing a jejunal biopsy on all individuals with suspected CD [34-39]. One approach defined five criteria, including clinical signs, four of which had to be fulfilled for a diagnosis of CD [38]. "
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    ABSTRACT: Background The objective of this study was to compare celiac disease (CD)– specific antibody tests to determine if they could replace jejunal biopsy in patients with a high pretest probability of CD. Methods This retrospective study included sera from 149 CD patients and 119 controls, all with intestinal biopsy. All samples were analyzed for IgA and IgG antibodies against native gliadin (ngli) and deamidated gliadin peptides (dpgli), as well as for IgA antibodies against tissue transglutaminase and endomysium. Results Tests for dpgli were superior to ngli for IgG antibody determination: 68% vs. 92% specificity and 79% vs. 85% sensitivity for ngli and dpgli, respectively. Positive (76% vs. 93%) and negative (72% vs. 83%) predictive values were also higher for dpgli than for ngli. Regarding IgA gliadin antibody determination, sensitivity improved from 61% to 78% with dpgli, while specificity and positive predictive value remained at 97% (P < 0.00001). A combination of four tests (IgA anti-dpgli, IgG anti-dpgli, IgA anti- tissue transglutaminase, and IgA anti-endomysium) yielded positive and negative predictive values of 99% and 100%, respectively and a likelihood ratio positive of 86 with a likelihood ratio negative of 0.00. Omitting the endomysium antibody determination still yielded positive and negative predictive values of 99% and 98%, respectively and a likelihood ratio positive of 87 with a likelihood ratio negative of 0.01. Conclusion Antibody tests for dpgli yielded superior results compared with ngli. A combination of three or four antibody tests including IgA anti-tissue transglutaminase and/or IgA anti- endomysium permitted diagnosis or exclusion of CD without intestinal biopsy in a high proportion of patients (78%). Jejunal biopsy would be necessary in patients with discordant antibody results (22%). With this two-step procedure, only patients with no CD-specific antibodies would be missed.
    Full-text · Article · Jan 2013 · BMC Gastroenterology
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    • "According to many studies [32–35], selective IgA deficiency should be considered during screening for CD especially with TTG IgA. TTG antibody is recommended as a screening test for CD by many authors [24, 36–38]. "
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    ABSTRACT: Background. Dental enamel defects (DEDs) are seen in celiac disease (CD). Aim was to detect frequency of CD among such patients. Methods. This study included 140 children with DED. They were tested for CD. Gluten-free diet (GFD) was instituted for CD patients. A cohort of 720, age and sex-matched, normal children represented a control group. Both groups were evaluated clinically. Serum calcium, phosphorus, alkaline phosphatase, serum IgA, and tissue transglutaminase (tTG) IgG and IgA types were measured. Results. CD was more diagnosed in patients with DEDs (17.86%) compared to controls (0.97%) (P < 0.0001). Majority of nonceliac patients showed grade 1 DED compared to grades 1, 2, and 3 DED in CD. Five children had DED of deciduous teeth and remaining in permanent ones. After 1 year on GFD, DED improved better in CD compared to nonceliac patients. Gastrointestinal symptoms did not vary between celiac and nonceliac DED patients. Lower serum calcium significantly predicted CD in this cohort. Conclusion. CD is more prevalent among children with DED than in the general population. These DEDs might be the only manifestation of CD; therefore, screening for CD is highly recommended among those patients especially in presence of underweight and hypocalcemia.
    Full-text · Article · Jun 2012
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