Citrulline as marker of atrophy in celiac disease.

Abstract

Dear Editor, We read with interest the paper from Papadia et al. [1] that suggests the potential role of the serum citrulline (CIT) level as biomarker of malabsorption. Intestinal CIT originates from the intestinal villi located in the proximal small bowel, which justifies its potential usefulness in the diseases associated with villous atrophy such as celiac disease (CD) [1]. Currently, the serological screening for suspected pediatric CD is based on the two major serological markers represented by the anti-transglutaminase type 2 (tTG) and by the anti-endomysial antibodies (EMA) [2]. Recently a third antibody against deamidated forms of gliadin peptides (DGP) has been identified that seems to be more sensitive in young children [2]. However, all these auto-antibodies may be undetectable in some clinical conditions [2]. In these cases, the diagnosis of CD may be supported by a screening tool not based on the evaluation of antibodies, but seemingly predictive of intestinal atrophy. From this perspective, the use of the CIT level might be helpful. We would like to report our experience with the CIT level in subjects highly suspected for CD. In 2011, we planned a prospective study to evaluate whether the serum CIT level might be included in a practical diagnostic work up of subjects with suggestive symptoms for CD. The setting of our study was the Hepatology, Gastroenterology and Nutrition Unit of ‘‘Bambino Gesu’’ Children’s Hospital in Rome. Between June 2011 and March 2012, all patients referred for suspected CD were enrolled. In all suspected CD subjects, a blood sample for IgA, tTG of IgA class, EMA, serum CIT and creatinine was taken. The biological sampling of CIT was made during stable clinical conditions and in a post-absorptive state and determined by RF-HPLC. In patients with IgA deficiency (total IgA B 5 mg %), we assessed the tTG of IgG class [3]. A biopsy was performed in all suspected CD, with suggestive symptoms isolated or associated with positive tTG/EMA. In agreement with the recommendations of the North American Society for Pediatric Gastroenterology Hepatology and Nutrition [3], type 3 specimens according to Marsh-Oberhuber classification [4] were considered characteristics of CD. The Marsh 1 and 2 lesions were considered nonspecific, but in line with the CD diagnosis in presence of positive tTG/EMA [3]. In patients with Marsh 3 lesions and negative tTG/EMA, HLA-DQ was assessed, and the symptoms were evaluated after starting a glutenfree diet (GFD). The patients with positive HLA-DQ2 and DQ8 and disappearance of the symptoms on a GFD were considered as CD cases. During the same period we enrolled all consecutive CD patients on a GFD. The inclusion criteria were the following: