Non-immunological biomarkers for assessment of villous abnormalities in patients with celiac disease
BACKGROUND:
Demonstration of villous abnormalities is an essential component of diagnosis of celiac disease (CeD) which requires duodenal biopsies. There is a need for non-invasive biomarker (s) which can predict the presence of villous abnormalities.
METHODS:
Levels of plasma citrulline, plasma I-FABP, and serum Reg1α were estimated in treatment naïve patients with CeD and controls. The levels of these biomarkers and their cyclical pattern was validated in a predicted model of enteropathy. Optimum diagnostic cutoff values were derived and the results were further validated in a prospective validation cohort.
RESULTS:
While level of plasma citrulline was significantly lower, the levels of plasma I-FABP and serum Reg1α were significantly higher in patients with CeD (n=131) in comparison to healthy (n=216) and disease controls (n=133), and their levels reversed after a gluten-free diet. In the model of predicted enteropathy (n=70), a sequential decrease and then increase in the level of plasma citrulline was observed; such a sequential change was not observed with I-FABP and Reg1α.
The diagnostic accuracy for prediction of presence of villous abnormality was 89% and 78% if citrulline level was <30μM/L and I-FABP levels was >1100pg/ml, respectively. The results were validated in a prospective validation cohort (n=104) with a sensitivity and specificity of 79.5% and 83.1%, respectively for predicting villous abnormalities of modified Marsh grade >2 at calculated cut-offs values of citrulline and I-FABP.
CONCLUSIONS:
Plasma citrulline <30μM/L is the most consistent, highly reproducible non-invasive biomarker which can predict the presence of villous abnormality and has the potential for avoiding duodenal biopsies in 78% patients suspected to have CeD.
Singh A, Verma AK, Das P, Prakash S, Pramanik R, Nayak B, Datta Gupta S, Sreenivas V, Kumar L, Ahuja V, Makharia GK.
J Gastroenterol Hepatol. 2019 Sep 9
doi: 10.1111/jgh.14 852.