Evaluation of the Utility of Amino Acid Citrulline as a Surrogate Metabolomic Biomarker for the Diagnosis of Celiac Disease

Abstract

Introduction: Citrulline is regarded as a biomarker for celiac disease (CD). Its utility for assessment and evaluation of additive predictive value for latent, potential CD and first degree relatives (FDRs) needs exploration. Method: Consecutive 558 index cases diagnosed as per European Society for Pediatric Gastroenterology and Nutrition (ESPGHAN) 2012 guidelines and their 1565 FDRs were evaluated over five and half year period. Serology negative FDRs at initial visit and follow ups were served as controls. HLA typing for DQ2 and DQ8 genotypes, along with plasma and dried blood spot (DBS) filter paper citrulline were evaluated. Results: Median plasma citrulline values were 20.1 and 37.33 µMol/l in cases and controls ( P < .001). Cut off values for Marsh grade 3a, 3b, and 3c were 35.0, 32.8, 25.26 µMol/l in CD patients and 36.51, 30.10, 25.26 µMol/l in biopsy proven FDR. Increasing trends of plasma citrulline levels with decreasing tTG-IgA levels were observed on follow up. Low plasma citrulline levels were observed with HLA DQ 2.5 genotype ( P < .05). Agreement between DBS and plasma citrulline was 94.8%. Conclusion: Citrulline is a good surrogate biomarker for identification of histopathological grade of damage, extent of mucosal recovery and has negative correlation with tTG-IgA. It identifies the silent and latent phase of CD. DBS citrulline provides adequate information and can be used for monitoring CD patients at remote locations.