Intestinal ferroportin expression in pediatric Crohn's disease

Abstract

Background: Anemia is a frequent complication of Crohn's disease (CD). The intestinal iron exporter ferroportin (FPN) is involved in both iron deficiency anemia and the anemia of chronic disease. To examine its role in CD, intestinal FPN expression was studied in subjects with and without CD.

Methods: Duodenal mucosal biopsies from 29 pediatric subjects with CD (n=19) and without CD (n=10) were obtained. FPN protein was measured using Western blot analysis and mRNA was assessed using quantitative real-time polymerase chain reaction (PCR).

Results: Intestinal FPN protein was higher in anemic CD subjects than in nonanemic CD subjects (P=0.01), while FPN mRNA levels were not different (P=0.66). In nonanemic CD subjects, erythrocyte sedimentation rate (ESR) (P=0.04), C-reactive protein (CRP) (P=0.03), and interleukin-6 (IL-6) (P=0.01) levels were elevated compared to controls. Nonanemic CD subjects had a lower median FPN protein than nonanemic controls, although it did not reach statistical significance (P=0.07). Median FPN mRNA was similar between groups (P=0.71). Although no correlation between FPN protein and IL-6 was noted, there was a strong negative correlation between serum iron and IL-6, both in subjects with CD (r=-0.88, P<0.0001) and those without anemia (r=-0.58, P=0.02).

Conclusions: Intestinal FPN protein is upregulated in anemic CD subjects, suggesting that iron deficiency or anemia is the driving force regulating FPN levels. A transporter distinct from FPN appears to be involved in the hypoferremia associated with the inflammatory process of CD.

FIGURE 1

Representative Western blot of FPN and actin protein levels in CD anemic and nonanemic patients.

FIGURE 2

Relation of FPN/actin to hemoglobin (Hgb) among CD patients. Data are stratified by, although not statistically adjusted for, anemia status (open circle = nonanemic, solid circle = anemic). Spearman rank correlation: −0.52 (P = 0.02).

FIGURE 3

Relation of FPN/actin to IL-6 among nonanemic patients. Data are stratified by, although not statistically adjusted for, CD (open circle = nonanemic control patients, solid circle = nonanemic CD patients). Spearman rank correlation: −0.45 (P = 0.08).

FIGURE 4

Relation of serum iron to IL-6 among CD patients. Data are stratified by, although not adjusted for, anemia status (open circle = nonanemic, solid circle = anemic). Spearman rank correlation: −0.88 (P < 0.0001).

FIGURE 5

Relation of serum iron to IL-6 among nonanemic patients, stratified by disease status (open circle = nonanemic control patients, solid circle = nonanemic CD patients). Spearman rank correlation: −0.58 (P = 0.02).