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Evaluation of mucosal status in the follow-up of pediatric patients with celiac disease: the role of serology

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Abstract

Recent guidelines suggest non-biopsy serology–based approach for the diagnosis of celiac disease; however, there is no evidence-based data regarding noninvasive follow-up of mucosal healing. The aim of this study is to investigate the efficacy of serology in reflecting mucosal status in the follow-up of pediatric patients with celiac disease. This is a validation study conducted at a university hospital. Patients who had biopsy proven celiac disease (Marsh III) at diagnosis, and had been followed-up for at least 12 months, were prospectively evaluated with duodenal biopsies. tTG-IgA and EMA tests were performed on the day of endoscopy. One hundred four patients with a mean age of 7.4 ± 4.02 years were included in the study. The sensitivity and specificity of tTG-IgA were 85.2% and 61% respectively, with a high negative predictive value (NPV) of 92.2% but a very low positive predictive value (PPV) of 43.4%. We found that a cutoff value of 68.5 U/mL for tTG-IgA had a sensitivity, specificity of 85.2% and 85.7% respectively. The AUC was 0.891. The sensitivity and specificity of EMA was 77.8% and 87% respectively, with a high NPV of 91.8% but low PPV of 67.7%.

Conclusion: This study suggests that negative tTG-IgA and/or EMA can be used as an indicator of mucosal improvement in the follow-up of pediatric patients with celiac disease. However, positive serology (i.e., < 10 × ULN) may be misleading in reflecting mucosal status in the follow-up of pediatric patients with celiac disease.

What is Known:

• The tissue transglutaminase IgA (tTG-IgA) and endomysium IgA (EMA) tests are widely used, sensitive and reliable diagnostic tests, but their role in monitoring adherence to dietary treatment in celiac patients has not yet been demonstrated.

• There is still no reliable and non-invasive marker of persistent villous atrophy or mucosal recovery.

What is New:

• Negative celiac serology detected in the follow-up of pediatric patients with celiac disease was successful in demonstrating histopathological mucosal healing.

• Positive celiac serology, which is highly reliable in the diagnosis of celiac disease, has not been successful in reflecting mucosal status when used in the follow-up of pediatric patients with celiac disease.

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Availability of data and material

The datasets analyzed during the current study are available from the corresponding author on reasonable request.

Code availability

Not applicable.

Abbreviations

AUC:

Area under curve

CD:

Celiac disease

EMA:

Endomysium IgA

ESPGHAN:

European Society of Pediatric Gastroenterology, Hepatology, and Nutrition

GFD:

Gluten-free diet

HT:

High titer

LT:

Low titer

NPV:

Negative predictive value

PPV:

Positive predictive value

ROC:

Receiver operating curve

tTG-IgA:

Tissue transglutaminase IgA

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Authors and Affiliations

  1. Div. of Pediatric Gastroenterology, Hepatology and Nutrition, Marmara University School of Medicine, Başıbüyük Campus, Maltepe Başıbüyük Yolu Sok. No:9/1, 34854, Maltepe, Istanbul, Turkey

    Ozlem Kalaycik Sengul, Bilge Sahin Akkelle, Burcu Volkan, Engin Tutar & Deniz Ertem

  2. Department of Public Health, Marmara University School of Medicine, Istanbul, Turkey

    Pınar Ay

  3. Department of Pathology, Marmara University School of Medicine, Istanbul, Turkey

    Cigdem Ataizi Celikel

Authors
  1. Ozlem Kalaycik Sengul
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  2. Bilge Sahin Akkelle
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  3. Pınar Ay
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  4. Burcu Volkan
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  5. Engin Tutar
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  6. Cigdem Ataizi Celikel
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  7. Deniz Ertem
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Contributions

Ozlem Kalaycik Sengul gathered and analyzed the data and wrote the manuscript for publication; Bilge Sahin Akkelle: gathered and analyzed the data; Pınar Ay: gathered and analyzed the data; Burcu Volkan: gathered and analyzed the data; Engin Tutar: drafted and revised the work; Cigdem Ataizi Celikel: revised the work; Deniz Ertem: designed the work, revised the manuscript, and approved the final version of work for publication. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Deniz Ertem.

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Ethics approval

Approval was obtained from the ethics committee of the Marmara University School of Medicine. The procedures used in this study adhere to the tenets of the Declaration of Helsinki (9022.78).

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Informed consent was obtained from the parents.

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Informed consent was obtained from the parents.

Competing interests

The authors declare no competing interests.

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Communicated by Peter de Winter

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Sengul, O.K., Akkelle, B.S., Ay, P. et al. Evaluation of mucosal status in the follow-up of pediatric patients with celiac disease: the role of serology. Eur J Pediatr 181, 3283–3289 (2022). https://doi.org/10.1007/s00431-022-04535-3

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  • DOI: https://doi.org/10.1007/s00431-022-04535-3

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