Intestinal fatty acid binding protein is a disease biomarker in paediatric coeliac disease and Crohn's disease

Michael Logan, Mary MacKinder, Clare Martha Clark, Aikaterini Kountouri, Mwansa Jere, Umer Zeeshan Ijaz, Richard Hansen, Paraic McGrogan, Richard K Russell, Konstantinos Gerasimidis, Michael Logan, Mary MacKinder, Clare Martha Clark, Aikaterini Kountouri, Mwansa Jere, Umer Zeeshan Ijaz, Richard Hansen, Paraic McGrogan, Richard K Russell, Konstantinos Gerasimidis

Abstract

Background: 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.

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: 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.

Trial registration: Clinical Trials.gov, NCT02341248. Registered on 19/01/2015.

Keywords: Biomarkers; Coeliac disease; Crohn’s disease; Inflammatory bowel disease; Paediatric; Ulcerative colitis.

Conflict of interest statement

KG received research grants, speakers’ fees and had conference attendance paid by Nutricia, Nestle, Abbott, Baxter and Dr Falk. UZI is supported by NERC NE/L011956/1. RH had received speakers/consultancy fees or conference support from Nutricia and 4D Pharma. RKR has received speaker’s fees, travel support, and/or participated in medical board meetings with Nestle, MSD Immunology, AbbVie, Dr Falk, Takeda, Napp, Mead Johnson, Nutricia & 4D Pharma.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
Schematic representation of study recruitment with sample type collection in each study group. Abbreviations mo: month, GFD: gluten-free diet
Fig. 2
Fig. 2
Boxplots A plasma, B urinary iFABP concentrations in Controls and patients with Coeliac during GFD; C plasma, D urinary iFABP concentration in Controls and patients with Colitis and Crohn’s during exclusive enteral nutrition. Coeliac: coeliac disease, ND: newly diagnosed, Crohn’s: Crohn’s disease, Controls: healthy control, mo: month, GFD: gluten-free diet, EEN: exclusive enteral nutrition. Urinary iFABP measurements are expressed after urinary creatinine correction, a: p < 0.05 compared with Controls; b: p < 0.05 compared with ND Coeliac
Fig. 3
Fig. 3
Individual value plot of pairwise plasma iFABP levels in patients with Crohn's during treatment with exclusive enteral nutrition

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