Faecal calprotectin is established as a clinically useful marker in IBD but won’t necessarily be the only non-invasive test for assessing mucosal healing in the future.
An Australian-led study in 157 children with Crohns’ disease has shown faecal S100A12 (FA12) is another highly sensitive and even more specific indicator.
The study, ancillary to the ImageKids study, assessed four faecal markers for their correlation with mucosal healing as measured by the simple endoscopic severity index for CD (SES-CD).
The study found all markers – faecal calprotectin (FC), FA12, faecal tumor pyruvate kinase isoenzyme type M2 (FM2-PK), and faecal osteoprotegerin (FOPG) – correlated with SES-CD and other constructs of disease activity.
“Of note, FC significantly distinguished remission and mild as well as mild and moderate disease but did not distinguish moderate and severe disease. In contrast FOPG did not distinguish differences between remission and mild, nor mild and moderate disease but did significantly distinguish between moderate and severe disease. FA12 had higher correlation with colonic disease than FC, but only a weak correlation with ileal SES-CD sub-score,” the study authors said.
They found FA12 predicted mucosal healing with 91% sensitivity and 87% specificity at a cut-off of 5 µg/g, whereas FC predicted mucosal healing with similar sensitivity of 90% but only 70% specificity using a cut-off of 500 µg/g.
Lead author Dr Steven Leach, a research fellow at the Sydney Children’s Hospital, told the limbic FA12 was slightly but not significantly better than calprotectin.
“My personal perspective on A12 is that it is probably similar or as good as calprotectin but calprotectin was there first, calprotectin has more evidence and calprotectin has an established commercial kit,” he said.
“In terms of A12 surpassing calprotectin, slightly better probably isn’t good enough to replace calprotectin as the go-to marker.”
However Dr Leach said the fact that A12 was a bit more specific to neutrophilic inflammation may have advantages in certain situations.
FA12 also had the advantage in paediatrics that, unlike FC, it was not elevated in early childhood.
Dr Leach said more work needed to be done to assess whether combining multiple markers together via various algorithms might advance the field.
“There is some history to that, for example in the field of cancer – predicting relapse with small RNA and DNA molecules in the blood. A single molecule doesn’t tell you much but you can combine a bunch of them together and get reasonably good predictions about the patient population with respect to relapse.”
He said there was ongoing work actively looking for other faecal markers.
FA12 had also been looked at in adults but is only used in the research context and isn’t yet close to being clinically useful, he added.