Faecal s-RAGE
Research type
Research Study
Full title
s-RAGE and calprotectin in samples of human faeces and blood
IRAS ID
157778
Contact name
S Cruickshank
Contact email
Sponsor organisation
University of Manchester
Duration of Study in the UK
0 years, 11 months, 31 days
Research summary
Faecal calprotectin has rapidly entered clinical practice as a marker for inflammatory bowel disease (IBD): an increased level, readily measured in faecal samples, correlates to an extent with gut inflammation. Calprotectin is a product of tissue damage and binds to the cells via a 'damage receptor' called RAGE (receptor of advanced glycation end products) to initiate inflammation. However, measuring calprotectin alone yields varying results and its sensitivity and specificity are therefore questionable. One reason that calprotectin may not perform well when used as a solitary biomarker is the lack of understanding of its biology. Our data implicate early upregulation of soluble RAGE (sRAGE), a decoy receptor that binds to calprotectin and prevents its pro-inflammatory action. We propose that the balance between calprotectin and its decoy receptor sRAGE is a critical factor in determining whether calprotectin will promote inflammation, and will present a far more valid biomarker when used with calprotectin than measuring calprotectin alone. It may also have utility in differentiating non-IBD causes of elevated faecal calprotectin such as polyps and tumours.
Proposed solution: We propose that the balance of calprotectin along with the decoy receptor sRAGE is the critical factor as to whether calprotectin is promoting inflammation. Thus, if both sRAGE and calprotectin are high, calprotectin would be bound by sRAGE and not switch on the pro-inflammatory pathways. In contrast if calprotectin were high but sRAGE was low, pro-inflammatory pathways would be initiated. Therefore, we wish to investigate whether assessing levels of both faecal calprotectin AND sRAGE (faecal or serum) and performing a correlative analysis will be a better prognostic tool in managing IBD.REC name
South Central - Berkshire B Research Ethics Committee
REC reference
14/SC/1413
Date of REC Opinion
24 Nov 2014
REC opinion
Favourable Opinion