Prospective Longitudinal Study

Use of Faecal Gluten Immunogenic Peptides to Monitor Children Diagnosed With Coeliac Disease During Transition to a Gluten-free Diet

Isabel Comino; Verónica Segura; Luis Ortigosa; Beatríz Espín; Gemma Castillejo; José Antonio Garrote; Carlos Sierra; Antonio Millán; Carmen Ribes-Koninckx; Enriqueta Román; Alfonso Rodriguez-Herrera; Jacobo Díaz; Jocelyn Anne Silvester; Ángel Cebolla; Carolina Sousa

Disclosures

Aliment Pharmacol Ther. 2019;49(12):1484-1492. 

In This Article

Abstract and Introduction

Abstract

Background: Treatment for coeliac disease is a lifelong strict gluten-free diet. Although guidelines recommend regular follow-up with dietary interviews and coeliac serology, these methods may be inaccurate.

Aim: To evaluate the usefulness of faecal gluten immunogenic peptides to support the diagnosis and to determine the adherence to the gluten-free diet in coeliac children.

Methods: Multicentre prospective observational study including 64 coeliac children. Faecal gluten peptides, and tissue transglutaminase and deamidated gliadin peptide antibodies were analyzed at diagnosis, and 6, 12 and 24 months thereafter. Gluten consumption was estimated from gluten peptide levels.

Results: Most children (97%) had detectable gluten peptides at diagnosis. On a gluten-free diet, the rate of gluten peptides increased from 13% at 6 months to 25% at 24 months. Mean estimated gluten exposure dropped from 5543 mg/d at diagnosis to 144 mg/d at 6 months, then increased to 606 mg/d by 24 months. In contrast, deamidated gliadin peptide antibodies normalised and only 20% had elevated tissue transglutaminase antibody by 24 months. The elevation of tissue transglutaminase antibody was more prolonged in patients with detectable gluten peptides (P < 0.05). Nevertheless, absolute levels of tissue transglutaminase antibody had low sensitivity to identify patients with detectable gluten peptides (P > 0.1). Dietitian assessment was only moderately correlated with gluten peptide detection (κ = 0.5).

Conclusions: Faecal gluten peptides testing may guide treatment of coeliac disease prior to diagnosis and during the assessment diet adherence. Further studies could determine if early identification of gluten exposure reduces the need for expensive/invasive investigations for non-responsive coeliac disease. ClinicalTrials.gov Number: NCT02711397.

Introduction

Coeliac disease is an immune-mediated disorder of the small intestine that affects ~1% of most populations.[1,2] This lifelong condition is initiated by exposure to dietary gluten in genetically susceptible individuals and can affect any organ or tissue. Consequently, a variety of gastrointestinal and extra-intestinal symptoms are observed, such as abdominal pain, malabsorption, anaemia, failure to thrive, osteoporosis and, occasionally, lymphoma.[3]

A lifelong gluten-free diet (GFD) is currently the only available treatment for coeliac disease and has been shown to improve quality of life substantially, both in patients initially presenting with gastrointestinal symptoms and in asymptomatic patients.[4] However, adherence to the GFD is not easy because gluten is ubiquitous and often not explicitly listed as an ingredient in food products. As a result, persistent symptoms and enteropathy are common among coeliac patients who are trying to follow a GFD. Specifically, research shows that 25%-40% of adults with coeliac disease have persistent enteropathy after 2 years on a GFD.[5–7] Children are thought to recover more quickly, and data suggests that 5%-19% of coeliac children on a GFD may have persistent enteropathy despite treatment with a GFD for at least 1 year.[8–13] Moreover, while the experts agree strict adherence to the GFD is crucial for the health of coeliac patients, there are no evidence-based recommendations regarding the most efficient way to assess GFD adherence.[14] Typically, dietary history, symptoms and serum antibody tests are used to assess non-adherence. However, a detailed dietary history is time consuming and requires the collaboration of a dietician, so in routine clinical practice, physicians often rely upon the patient's own subjective assessment of dietary adherence, or the presence of adverse symptoms to guide dietician referral. The difficulty with this approach is that many non-adherent patients may be asymptomatic. In addition, if patients do have symptoms, these may be as a result of coexisting disorders, such as irritable bowel syndrome, microscopic colitis or pancreatic insufficiency.[15] Concerningly, although coeliac antibody tests are widely used for routine monitoring of coeliac patients, these tests were never approved for this purpose and have low sensitivity in detection of persistent mucosal lesion in coeliac patients on a GFD.[16] Therefore, none of these methods offer an accurate measure of dietary adherence. Whilst duodenal biopsy is considered the 'gold standard' for assessment of celiac disease activity,[17] certain associations, such as the European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) Coeliac Disease working group strongly advises against regular re-biopsy in children on a GFD, due to unnecessary risks for the patient, negative impacts on quality of life, and pointless high medical costs.[18]

Monoclonal antibodies capable of sensitively and specifically detecting gluten immunogenic peptides (GIP) have been used to develop assays for detecting inadvertent gluten consumption by measuring GIP in human samples (faeces and urine). These assays may be a practical method to assess dietary adherence in coeliac patients.[19–21] GIP are resistant to gastrointestinal digestion and account for immunogenic reactions in T cells of patients with coeliac disease.[22] Unlike traditional methods to monitor GFD adherence which only evaluate the consequences of GFD transgressions, this non-invasive method enables a direct and quantitative assessment of gluten exposure. A recent study demonstrated the clinical usefulness of GIP as a marker of GFD adherence in patients following a GFD for at least 1 year.[20] Although it is well known that compliance with the GFD overall decreases on long term follow-up, however strict adherence to a GFD in the first year after the diagnosis crucial to favour mucosal recovery. For this reason, the aim of the present study was to evaluate the measurement of GIP in stools as a marker of GFD adherence in newly diagnosed coeliac children in a prospective multicentre clinical trial. Furthermore, this was compared to traditional methods used to assess GFD adherence: dietitian review of four-day food recrod and coeliac serology (tissue transglutaminase, tTG and deamidated gliadin peptide antibodies, DGP).

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