Study Explores Potential Biomarker for Celiac Disease in Children

There is a clinical need to develop biomarkers of small bowel damage in coeliac disease and Crohn’s disease. This study evaluated intestinal fatty acid binding protein (iFABP), a potential biomarker of small bowel damage, in children with coeliac disease and Crohn’s disease.

BMC Gastroenterology ¹

Coeliac disease alongside inflammatory bowel disease (IBD) which includes both Crohn’s disease and ulcerative colitis are chronic diseases of the gastrointestinal tract (GIT) . These diseases share similar presenting clinical symptoms including weight loss, malnutrition, and abdominal pain .

The gold standard for assessment of intestinal damage in coeliac disease and IBD remains endoscopy coupled with biopsy .

However, as endoscopy is an invasive procedure, routine assessment of disease activity of these diseases relies upon patient self-reported symptoms, along with blood and faecal inflammatory biomarkers which often do not reflect histological damage or recovery following therapy.

Faecal calprotectin (FC) has now become the mainstream marker of bowel inflammation in patients with IBD . However, there are conflicting reports surrounding the utility of FC in assessing intestinal inflammation in patients with isolated small bowel Crohn’s disease.

In patients with coeliac disease, antibody tests such as the anti-transglutaminase antibodies (TGA), may not accurately reflect ongoing small bowel inflammation, due in part to the long half-life they take to decrease following introduction of a gluten-free diet (GFD).

Currently, there are no reliable or specific laboratory biomarkers to assess inflammation within the small bowel in patients with coeliac disease or IBD, particularly Crohn’s disease.

Intestinal fatty acid binding protein (iFABP) is a small 5 kDa protein accounting for 1–2% of total cytosolic protein within enterocytes.

The tissue specificity of iFABP, as well its ability to be measured in readily available non-invasive samples (e.g. urine) make it an attractive candidate biomarker of tissue involvement/damage in the upper GIT.

Previous reports have shown that patients with IBD and coeliac disease have significantly higher concentration of circulating iFABP compared with healthy controls (Controls) but evidence has not always been consistent .

The concentration of iFABP in patients with Crohn’s disease has also been shown to correlate with the pro-inflammatory cytokine tumour necrosis factor (TNF)-α and significantly decrease during treatment with anti-TNF-α therapy.

Methods

The concentration iFABP was measured in plasma and urine of children with ulcerative colitis, coeliac disease, and Crohn’s disease at diagnosis and from the latter two groups after treatment with gluten free diet (GFD) or exclusive enteral nutrition (EEN), respectively. Healthy children (Controls) were also recruited.

Results

138 children were recruited.

Plasma but not urinary iFABP was higher in patients with newly diagnosed coeliac disease than Controls (median [Q1, Q3] coeliac disease: 2104 pg/mL 1493, 2457] vs Controls: 938 pg/mL [616, 1140], p = 0.001).

Plasma or urinary iFABP did not differ between patients with coeliac on GFD and Controls. Baseline iFABP in plasma decreased by 6 months on GFD (6mo GFD: 1238 pg/mL [952, 1618], p = 0.045).

By 12 months this effect was lost, at which point 25% of patients with coeliac disease had detectable gluten in faeces, whilst tissue transglutaminase IgA antibodies (TGA) continued to decrease.

At diagnosis, patients with Crohn’s disease had higher plasma iFABP levels than Controls (EEN Start: 1339 pg/mL [895, 1969] vs Controls: 938 pg/mL [616, 1140], p = 0.008).

iFABP did not differ according to Crohn’s disease phenotype. Induction treatment with EEN tended to decrease (p = 0.072)

iFABP in plasma which was no longer different to Controls (EEN End: 1114 pg/mL [689, 1400] vs Controls: 938 pg/mL [616, 1140], p = 0.164).

Plasma or urinary iFABP did not differ in patients with ulcerative colitis from Controls (plasma iFABP, ulcerative colitis: 1309 pg/mL [1005, 1458] vs Controls: 938 pg/mL [616, 1140], p = 0.301; urinary iFABP ulcerative colitis: 38 pg/mg [29, 81] vs Controls: 53 pg/mg [27, 109], p = 0.605).

Conclusions

This study highlights the utility of iFABP measurements in plasma but not in urine, in helping in monitoring compliance during GFD, with potentially better performance when compared to other mainstream biomarkers.

The role of plasma iFABP in Crohn’s disease and the effect of induction treatment might also be promising but warrants further investigation.

Plasma, but not urinary iFABP is a candidate biomarker with better fidelity in monitoring compliance during GFD than TGA. The role of plasma iFABP in Crohn’s disease is promising but warrants further investigation.