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P606 Intestinal fatty acid binding protein parallels temporal changes in Harvey-Bradshaw Index and TNFα in response to infliximab in Crohn's disease

Hellström P.M., Al-Saffar K.A., Tartera Diaz H., Ram G.V., Webb D.-L.

Uppsala University, Department of Medical Sciences, Uppsala, Sweden

Background

Intestinal fatty acid binding protein (I-FABP) is an intracellular protein, with a low molecular weight of approximately 15 kDa, that plays an important role in the transportation and metabolism of long-chain fatty acids in the intestines. I-FABP is selectively expressed in the intestinal epithelium and indicates small intestinal barrier integrity.

The present aims were to determine if

1. I-FABP is elevated in active Crohn's disease (CD),

2. I-FABP parallels anti-TNFα antibody (infliximab) induced lowering of TNFα and Harvey-Bradshaw Index (HBI) as an indicator of mucosal healing, and

3. determine I-FABP distribution along the human gut.

Methods

Biobanked serum was analyzed from 10 CD patients collected during their first three consecutive infliximab treatments (years 2000–2005) with matched pre-treatment and follow-up samples one week after each treatment and corresponding HBI data. I-FABP reference range was established from 30 healthy subjects with normal gut permeability. CD patient TNFα was compared to an in-house reference range (61 healthy subjects). I-FABP and TNFα were measured by ELISA. Paraffin embedded healthy tissue sections were used for I-FABP immunohistochemistry in order to localize expression of I-FABP along the gastrointestinal tract.

Results

CD patient TNFα levels were 1.5 fold higher (2.34±0.22 vs 1.58±0.09 ng/L, p<0.001) than healthy subjects, while I-FABP was 2.4 fold higher (2.02±0.23 vs 0.86±0.17 μg/L, p<0.001), with lower levels at first follow-up (p<0.05). Combining all infusion/follow-up pairs also gave a significant difference in I-FABP (p<0.005, n=30). Immunoreactivity to I-FABP was expressed solely in the epithelium of stomach, small intestine and colon, with highest expression in jejunum and ileum.

Conclusion

I-FABP is elevated in active CD with a magnitude comparable to TNFα. On treatment with infliximab temporal parallel falls of TNFα, HBI and I-FABP were found, with a subsequent rise over weeks until next infliximab treatment. Hence, I-FABP may be useful as an intestine-selective prognostic marker for mucosal healing.