The decrease of IGF-I, IGF-binding protein-3 and bone alkaline phosphatase isoforms during gluten challenge correlates with small intestinal inflammation in children with coeliac disease.

OBJECTIVE: In children with coeliac disease, the ingestion of gluten causes small intestinal inflammation and a clinical picture of malabsorption, weight reduction and short stature. Decreased alkaline phosphatase (ALP) during gluten challenge was found in a previous study. ALP is a marker of bone formation and ALP activities are correlated with growth velocity. The aim of this study was to characterise the previously observed decrease of total ALP by investigating three specific bone ALP isoforms (bone/intestinal, B1 and B2) and three specific liver ALP isoforms (L1, L2 and L3) and, moreover, to correlate these ALP isoforms with other growth factors and growth markers. In addition, we also studied the association with possible weight changes, small intestinal mucosa inflammation, sex, age and gluten dose during gluten challenge. MATERIALS AND METHODS: Bone and liver ALP isoforms, IGF-I, IGF-binding protein (IGFBP)-3 and serum cross-linked carboxy-terminal telopeptide of type I collagen (ICTP) were measured together with change in weight and small intestinal mucosa histopathology in 54 children with earlier enteropathy who participated in a 4-week gluten challenge. RESULTS: We observed a decreased total ALP activity after 4 weeks of gluten challenge, 7.8+/-1.8 to 6.5+/-1.7 microkat/l (means +/- s.d.), which was mainly due to a reduction of the bone ALP isoforms. The sum of all three bone ALP isoforms decreased from 6.3+/-1.7 to 5.1+/-1.6 microkat/l. The decreased activities of the bone ALP isoforms correlated with the observed reductions of IGF-I (r=0.74, P<0.001), IGFBP-3 (r=0.51, P<0.001) and ICTP (r=0.57, P<0.001). The decrease of the growth factors and growth markers correlated with weight reduction, but when influences from the change in weight were adjusted for, the partial correlation of the small intestinal mucosa inflammation was significant for IGF-I (r=-0.56, P<0.001) and IGFBP-3 (r=-0.55, P<0.001). CONCLUSION: The decrease of total ALP was due to a reduction of bone ALP. The decrease of IGF-I and IGFBP-3 was independently correlated with weight change and small intestinal inflammation.

Two different doses of gluten show a dose-dependent response of enteropathy but not of serological markers during gluten challenge in children with coeliac disease.

UNLABELLED: In order to study dose-dependency in histopathological reactions and in changes of serological markers of mucosal relapse, gluten challenge was performed with two defined amounts of gluten in 54 children with earlier enteropathy. Gluten was provided in the form of powder and the patients were randomly allotted to either 0.2 (group A, n = 27) or 0.5 (group B, n = 27) grams per kg body weight per day. At the start and after 4 wk of challenge a small intestinal biopsy was performed. Biopsy specimens were evaluated, in accordance with defined criteria, graded and summarized in an enteropathy score. Blood was sampled at the start and after 2 and 4 wk of challenge. Serum levels of anti-gliadin antibodies (AGA) and anti-endomysium antibodies (EmA) were measured. Within 4 wk of challenge, 24 out of 27 patients in group A and all patients in group B had relapsed. After increasing the gluten dose to 0.5 g/kg/d during the subsequent 4 wk, the three non-relapsing patients also relapsed. CONCLUSION: The severity of mucosal inflammation was significantly higher for group B (p = 0.04) indicating a dose-related severity of the enteropathy. No significant difference was found for maximum AGA level, or in the proportion of patients that converted to pathological values for AGA or EmA.