Brief Article
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World J Gastroenterol. Aug 28, 2012; 18(32): 4399-4403
Published online Aug 28, 2012. doi: 10.3748/wjg.v18.i32.4399
Tissue transglutaminase levels above 100 U/mL and celiac disease: A prospective study
Amani Mubarak, Victorien M Wolters, Frits HJ Gmelig-Meyling, Fiebo JW ten Kate, Roderick HJ Houwen
Amani Mubarak, Victorien M Wolters, Roderick HJ Houwen, Department of Pediatric Gastroenterology, Wilhelmina Children’s Hospital, University Medical Center Utrecht, 3508 AB Utrecht, The Netherlands
Frits HJ Gmelig-Meyling, Department of Immunology, University Medical Center Utrecht, 3508 AB Utrecht, The Netherlands
Fiebo JW ten Kate, Department of Pathology, University Medical Center Utrecht, 3508 AB Utrecht, The Netherlands
Author contributions: Mubarak A coordinated the study, selected patients for inclusion, performed the data-analysis and wrote the article; Wolters VM selected patients for inclusion and reviewed the article; Gmelig-Meyling FHJ supervised the performance of serological testing and reviewed the article; ten Kate FJW classified all biopsies and reviewed the article; and Houwen RHJ supervised the whole project and reviewed the article.
Correspondence to: Dr. Amani Mubarak, Department of Pediatric Gastroenterology, Wilhelmina Children’s hospital, University Medical Center Utrecht, KE 01.144.3, PO Box 85090, 3508 AB Utrecht, The Netherlands. a.mubarak@umcutrecht.nl
Telephone: +31-88-7555294 Fax: +31-88-7555348
Received: June 8, 2012
Revised: July 24, 2012
Accepted: July 28, 2012
Published online: August 28, 2012
Abstract

AIM: To investigate whether a tissue-transglutaminase antibody (tTGA) level ≥ 100 U/mL is sufficient for the diagnosis of celiac disease (CD).

METHODS: Children suspected of having CD were prospectively included in our study between March 2009 and September 2011. All patients with immune globulin A deficiency and all patients on a gluten-free diet were excluded from the study. Anti-endomysium antibodies (EMA) were detected by means of immunofluorescence using sections of distal monkey esophagus (EUROIMMUN, Luebeck, Germany). Serum anti-tTGA were measured by means of enzyme-linked immunosorbent assay using human recombinant tissue transglutaminase (ELiA Celikey IgA kit Phadia AB, Uppsala, Sweden). The histological slides were graded by a single experienced pathologist using the Marsh classification as modified by Oberhuber. Marsh II and III lesions were considered to be diagnostic for the disease. The positive predictive values (PPVs), negative predictive values (NPVs), sensitivity and specificity of EMA and tTGA along with their 95% CI (for the cut off values > 10 and ≥ 100 U/mL) were calculated using histology as the gold standard for CD.

RESULTS: A total of 183 children were included in the study. A total of 70 (38.3%) were male, while 113 (61.7%) were female. The age range was between 1.0 and 17.6 years, and the mean age was 6.2 years. One hundred twenty (65.6%) patients had a small intestinal biopsy diagnostic for the disease; 3 patients had a Marsh II lesion, and 117 patients had a Marsh III lesion. Of the patients without CD, only 4 patients had a Marsh I lesion. Of the 183 patients, 136 patients were positive for EMA, of whom 20 did not have CD, yielding a PPV for EMA of 85% (95% CI: 78%-90%) and a corresponding specificity of 68% (95% CI: 55%-79%). The NPV and specificity for EMA were 91% (95% CI: 79%-97%) and 97% (95% CI: 91%-99%), respectively. Increased levels of tTGA were found in 130 patients, although only 116 patients truly had histological evidence of the disease. The PPV for tTGA was 89% (95% CI: 82%-94%), and the corresponding specificity was 78% (95% CI: 65%-87%). The NPV and sensitivity were 92% (95% CI: 81%-98%) and 97% (95% CI: 91%-99%), respectively. A tTGA level ≥ 100 U/mL was found in 87 (47.5%) patients, all of whom were also positive for EMA. In all these 87 patients, epithelial lesions confirming CD were found, giving a PPV of 100% (95%CI: 95%-100%). The corresponding specificity for this cut-off value was also 100% (95% CI: 93%-100%). Within this group, a total of 83 patients had symptoms, at least gastrointestinal and/or growth retardation. Three patients were asymptomatic but were screened because they belonged to a group at risk for CD (diabetes mellitus type 1 or positive family history). The fourth patient who lacked CD-symptoms was detected by coincidence during an endoscopy performed for gastro-intestinal bleeding.

CONCLUSION: This study confirms based on prospective data that a small intestinal biopsy is not necessary for the diagnosis of CD in symptomatic patients with tTGA ≥ 100 U/mL.

Keywords: Celiac disease; Diagnosis, Serology; Anti-tissue-transglutaminase antibodies; Anti-endomysium antibodies