We read with great interest the article by Lebwohl et al. regarding the need for objective biomarkers to predict morbidity and mortality in coeliac disease (CD). Villous atrophy is a hallmark of CD, and it has been postulated that defective mucosal detoxification of carcinogens in atrophic villi leads to the observed increased incidence of cancer in patients with poorly controlled CD.
While the authors found that persistent villous atrophy was not a suitable prognostic biomarker for mortality in CD, they nonetheless reported a trend (P = 0.2542) towards increased mortality from malignancies.
The Adnab-9 antibody was developed to detect premalignant lesions in the gastrointestinal tract, and has been validated in various studies.[4-6] To test whether Adnab-9 can be used to estimate risk of developing malignancy in patients with CD, we measured levels of Adnab-9 antigen in stool supernatants from a small cohort of CD patients on normal or gluten-free diets (GFD) (Figure 1).
The results show that while patients on normal diets have widely variable levels of Adnab-9 antigen in stool water, all patients on GFD but one had very low levels of Adnab-9 binding. This decrease parallels the greatly diminished risk for developing GI malignancies such as oesophageal cancer or small bowel adenocarcinoma in patients with GFD. Together, this suggests that Adnab-9 might be a novel marker to predict risk of malignancy in patients with CD.
In summary, there is clear need for objective biomarkers to predict cancer risk in patients with CD. Our results suggest that Adnab-9 immunoreactivity might serve this purpose. The observed decrease in Adnab-9 binding with GFD was similar to previously observed decrease in anti-tissue transglutaminase antibodies. However, as Adnab-9 is a premalignant marker, we hypothesise that Adnab-9 detection in stool water may be a more accurate and specific means to detect patients with CD who are at high risk to develop small bowel cancers. Prospective studies are needed to further investigate these ideas.