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

Results

The study population consisted of 64 children (21 males and 43 females) with a median age of 4 years (IQR 1.5-9 years; Table 1). Participant retention was 94% at 6 months, 78% at 12 months and 55% at 24 months (the most common reason for loss to follow-up were: moving out of the study area, not attending follow-up visits and forgetting to collect samples).

Detection of GIP in Stool

At the initial visit, before starting the GFD, during the expected gluten challenge for diagnosis, 62 (97%) patients had detectable GIP in the provided stool sample. After diagnosis and treatment with a GFD, 13 (23%) of patients had detectable levels of GIP in at least one visit, whereas 11 (20%) were noncompliant according to the questionnaire. Overall, 11% of all coeliac patients were noncompliant by both methods, 48% were gluten free by both methods (κ = 0.5) and 39% were discordant. In general, GFD adherence rates declined as the study progressed (Figure 1A,B). The rate of GIP positive stools was 13% at 6 months, 18% at 12 months and 25% at 24 months. Notably, 46% of transgressors had detectable GIP at two or more follow-up visits (Figure 1C).

Figure 1.

Concentration of gluten immunogenic peptides (GIP) in stools of patients with newly diagnosed coeliac disease during monitoring of the gluten-free diet. (A) Levels of faecal GIP at the basal and follow-up visits (basal, 6, 12 and 24 mo). (B) Levels of faecal GIP at 6, 12 and 24 mo. (C) Levels of GIP in transgressing patients in the different follow-up visits (log scale). GIP, gluten immunogenic peptides; LOQ, limit of quantification

The rate of GIP positive stools during follow-up increased with age (P = 0.041). Specifically, GIP were detected in stools from 6% of children with coeliac disease before 2 years of age, and in 24% and 35% in those diagnosed at 2–6 years and at an older age, 7–18 years, respectively (Figure 2).

Figure 2.

Gluten immunogenic peptides detection on a GFD according to patient age. Percentage distribution of stools collected during a GFD with detectable GIP according to age. GIP, gluten immunogenic peptides. GFD, gluten-free diet

Eleven participants (17%) reported no classic symptoms prior to diagnosis with coeliac disease and instead were biopsied for atypical symptoms or laboratory abnormalities. The rate of dietary transgressions in this group was 33% compared to 19% for the group diagnosed due to classical coeliac disease symptoms (P = 0.57).

Estimated Gluten Ingestion

An estimate of gluten consumption by coeliac patients following a GFD was determined by measuring GIP in stool. Both the mean and median values for each visit are reported due to the non-normal distribution of gluten ingestion (Table 2). At diagnosis, estimated daily gluten consumption was 5543 mg (mean) with a 95% CI [4345–6741 mg] and 3882 mg (median). During transition to a GFD, we found 342 mg gluten (mean), 95% CI [67–616 mg] and 104 mg (median) in samples tested. There was a trend toward increased gluten consumption during the follow-up period. After diagnosis, estimated gluten exposure was (mean/median) 144/99 mg/d at 6 months, 452/105 mg/d at 12 months, and 606/117 mg/d at 24 months.

Correlation Between Faecal GIP and Serum Antibodies

Serum tTG and DGP antibodies levels declined during follow-up (Figure 3A). For tTG antibody, 48% were positive at the 6 months visit, 34% at 12 months and 20% at 24 months. For DGP antibody, positive results were obtained in 11% at 6 months, 5% at 12 months and 0% at 24 months. In contrast, rates of GIP positive stools showed an upward trend during the follow-up period and were highest at the last visit (Figure 3B).

Figure 3.

Evolution of GIP, tTG and DGP antibodies in patients with newly diagnosed coeliac disease. (A) tTG and DGP antibody levels vs time. (B) Percentage of dietary transgressions according GIP, tTG and DGP antibodies during the study period. DGP, deamidated gliadin peptide antibody; tTG, tissue transglutaminase antibody; GFD, gluten-free diet; GIP, gluten immunogenic peptides. The cut-off >10 U/mL

Considering the absolute values for both tTG and DGP antibodies at each visit, we did not find concordance for GIP, with very low kappa values, far from statistical significance (P > 0.1). Nor was there statistical concordance when using dichotomous terms that is, positive when GIP were detected at least one follow-up visit (6, 12, or 24 months), and negative when GIP were not detected during follow-up (Table 3). The kappa values were very low, far from statistical significance (P > 0.1) in all cases.

Figure 3 displays the absolute reduction in the tTG antibody titer after 6 months (Figure 3A) and 12 months (Figure 3B) of GFD therapy. We also found a substantial, significant, reduction in the tTG antibody with respect to the basal (diagnosis) levels; this trend was stronger in the group of patients adhering to the GFD, as demonstrated by the negative GIP, with reductions of 103 U/mL (IQR 50–122) vs 28 U/mL (IQR 12–63) in the positive GIP patients after 6 months of GFD (P = 0.028) (Figure 4A). This differential kinetic behaviour of the tTG antibody in the two groups was also observed at 12 months of treatment: 116 U/mL (IQR 61–127) in adherents vs 48 U/mL (IQR 31–101) (P = 0.038) in non-adherents (Figure 4B).

Figure 4.

Absolute reduction of tTG antibody level at (A) 6 mo and (B) 12 mo in patients with detectable GIP and non GIP detected. GIP, gluten immunogenic peptides; tTG, tissue transglutaminase

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