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Non-immunological biomarkers for assessment of villous abnormalities in patients with celiac disease


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.


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.


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.


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.

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