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Tissue transglutaminase levels above 100 U/mL and celiac disease: a prospective study
Amani Mubarak1, Victorien M Wolters, Frits H J Gmelig-Meyling
1Department of Pediatric Gastroenterology, Wilhelmina Children's Hospital, University Medical Center Utrecht, 3508 AB Utrecht, The Netherlands. a.mubarak@umcutrecht.nl
Insights
A tissue-transglutaminase antibody (tTGA) level of 100 U/mL or higher is sufficient for diagnosing celiac disease (CD) in children. This finding indicates that a small intestinal biopsy may not be necessary for diagnosis in symptomatic patients.
Area of Science:
- Pediatric Gastroenterology
- Immunology
- Gastroenterology
Background:
- Celiac disease (CD) is an autoimmune disorder triggered by gluten ingestion.
- Accurate diagnosis of CD is crucial for effective management and prevention of complications.
- Tissue-transglutaminase antibody (tTGA) testing is a key serological marker for CD diagnosis.
Purpose of the Study:
- To evaluate if a tissue-transglutaminase antibody (tTGA) level of ≥ 100 U/mL is adequate for diagnosing celiac disease (CD).
- To assess the diagnostic accuracy of tTGA and anti-endomysium antibodies (EMA) compared to histology.
- To determine if invasive biopsy can be omitted in specific pediatric CD cases.
Main Methods:
- Prospective study of 183 children suspected of having CD (March 2009-September 2011).
- Exclusion of patients with IgA deficiency or on a gluten-free diet.
- Measurement of EMA and tTGA levels; histological grading using Marsh classification (Marsh II/III diagnostic for CD).
Main Results:
- Histological confirmation of CD in 120 (65.6%) of 183 children.
- tTGA levels ≥ 100 U/mL were observed in 87 patients (47.5%), all EMA-positive.
- A tTGA level ≥ 100 U/mL demonstrated 100% positive predictive value and 100% specificity for diagnosing CD.
Conclusions:
- A tTGA level of ≥ 100 U/mL, combined with EMA positivity, is highly accurate for diagnosing CD in children.
- Prospective data suggest that small intestinal biopsy may not be required for CD diagnosis in symptomatic children with tTGA ≥ 100 U/mL.
- This finding can potentially streamline the diagnostic process for pediatric celiac disease.
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.
