Iron metabolism, Anaemia and Coeliac disease.
Research type
Research Study
Full title
Duodenal Transferrin Receptor Expression in Coeliac Disease: Pilot Study
IRAS ID
208858
Contact name
David Sanders
Contact email
Sponsor organisation
Sheffield Teaching Hospitals NHS FT
Duration of Study in the UK
0 years, 4 months, 1 days
Research summary
In coeliac disease, ectopic expression of the transferrin receptor (TfR; CD71) on the luminal membrane of enterocytes has been shown to promote ‘protected’ retrotranscytosis of IgA/ gliadin immune complexes from lumen to lamina propria. Within the lamina propria, the intact IgA/ gliadin immune complexes are presented to antigen presenting cells which stimulates the adaptive immune response. In otherwise healthy individuals, TfR mRNA is upregulated in response to reduced iron stores. Iron deficiency is a common manifestation of active coeliac disease and is usually attributed to a decreased absorptive surface at the duodenum. Whether coeliac patients with iron deficiency have an exaggerated inflammatory response as a result of increased ectopic enterocyte TfR expression in comparison with coeliac patients with normal iron stores has not been examined before.
The aim of the proposed pilot is to determine whether there is differential enterocyte expression of the TfR, as well as key inflammatory stimuli, in iron deficient and non-iron deficient coeliac patients. We plan to evaluate TfR, IFN-gamma, TNF-alpha, IL-15, IL-6 and ferritin heavy chain expression in historical formalin-fixed paraffin-embedded (FFPE) duodenal tissue sampled from 10 patients with active coeliac disease and iron deficiency, 10 patients with active coeliac disease and normal iron stores and 10 non-coeliac controls with normal iron stores. mRNA levels will be determined by quantitative PCR and protein expression by immunohistochemistry. This is a pilot study that will provide data to support the lead investigators PhD funding proposal.
REC name
HSC REC B
REC reference
16/NI/0118
Date of REC Opinion
6 Jun 2016
REC opinion
Favourable Opinion