Letter: serum I-FABP as marker for enterocyte damage in first-degree relatives of patients with coeliac disease.

Abstract

Intestinal fatty acid binding protein (IFABP) is a small protein found in the cytosol of enterocytes. IFABP has been proven as a sensitive marker of intestinal epithelium damage in several diseases. Adriaanse et al. reported that serum IFABP levels are elevated in patients with untreated coeliac disease (CD), and correlate with the severity of villous atrophy.1 First-degree relatives (FDRs) of CD patients represent a group of individuals at risk for CD. The screening of this population revealed a high percentage of first-degree relatives showing lymphocytic enteritis (Marsh I) and/or gastrointestinal symptoms.2 However, it is not clear if patients with Marsh I may have enterocyte damage with associated malabsorption.3 The identification of these first-degree relatives may be helpful to prescribe a gluten-free diet. We evaluated the utility of serum IFABP levels for the detection of enterocyte damage in those first-degree relatives with lymphocytic enteritis. The study received Ethical Committee approval from the University Hospital of León. We selected 67 adult first-degree relatives (medium age 42 years and 59% female). All participants presented negative serologic markers of CD and 51/67 showed the HLA-DQ2 or DQ8 heterodimer. Results showed that 39% of individuals had increased intraepithelial lymphocytes (IEL) in duodenal biopsies (>25 IEL/100 entrecotes), while the remaining 61% showed normal intestinal histology. Quantification of IFABP in peripheral blood serum was performed by enzyme-link immunosorbent assay using a specific anti-human IF BP antibody.1 Serum IFABP levels were significantly higher in individuals with HLADQ2/DQ8 when compared to the nongenetic risk group (427.18 ± 164.6 pg/mL vs. 324.95 ± 108.1 pg/mL, P = 0.023). We also found elevated serum IFABP levels in relatives with increased intraepithelial lymphocytes, when compared to those with normal duodenal biopsies (470.30 ± 118.6 pg/mL vs. 359.93 ± 189.4 pg/mL). Finally, we noticed that differences in serum IFABP levels were even higher when Marsh I and positive genetic markers relatives were pooled and compared to the rest of participants (521.01 ± 177.6 pg/mL vs. 352.45 ± 119.4, P = 0.001). Serum IFABP levels compatible with intestinal damage were present in 80% of individuals with Marsh I and HLADQ2/D8 haplotypes while only a 34% of the remaining participants showed high values of IF BP (P = 0.001). We also studied the presence of digestive symptoms such as dyspepsia, diarrhoea, and bloating, which were found in 35/67 (52%) of the subjects. The IFABP serum levels were slightly higher in those without clinical manifestations but the difference was not significant. (438.93 ± 175.1 pg/mL vs. 360.73 ± 131.9 pg/mL, P = 0.08). No differences were either reported in IF BP levels related to H. pylori infection. In our study, we have observed that intestinal damage in first-degree relatives of coeliac patients could be detected measuring IFABP serum levels. Furthermore, intestinal damage is related to the presence of high-risk genetic markers and increased intraepithelial lymphocytes. It is known that early forms of CD without villous atrophy are also associated with long-term complications such as malabsorption with osteopenia and anaemia.4, 5 An evidence of epithelial disruption associated to an increase in the IFABP levels supports this idea. It would be interesting to carry out prospective studies to evaluate the prognosis, clinical consequences and the influence of the gluten-free diet on these findings in first-degree relatives. Declaration of personal interests: None. Declaration of funding interests: This study was funded in part by a grant from the Instituto de Salud Carlos III, Fondo de Investigación Sanitaria (Ref. PI13/01133), cofunded by FEDER (European Regional Development Fund).