LAUSR

Dear Editor, We read the letter written by Barbara Zanini, Anna Bozzola, and Vincenzo Villanacci regarding our paper titled BDiscriminant value of IEL counts and distribution pattern through the spectrum of gluten sensitivity: a simple diagnostic approach^ [1], with great interest. We are glad to see that our paper has incited a pleasant discussion among experts in which we would like to participate and clarify certain points raised by Zanini et al. in their letter. Ours was a retrospective study, so we do not know whether the non-celiac IELosis group corresponds to NCGS, as the diagnosis depends on the exclusion of the other causes of IELosis together with response to GFD followed by a single or doubleblind placebo-controlled gluten challenge [2]. It seems likely, however, that some of our cases may indeed be NCGS, based on their symptoms, negative serology, and normal or mildly increased IEL counts in the duodenal biopsy [1]. Nevertheless, we did not compare the histology of non-celiac IELosis with the histological features proposed by Zanini et al. [3] for NCGS, but rather based our discussion on the assumption that at least some of our non-celiac IELosis cases, if evaluated by Salerno Experts’ criteria [2], could be true NCGS, especially, those with an IEL count < 25/100 enterocytes. Regarding their histological assessment, Zanini et al. have elegantly proposed that NCGS mucosa showed increased eosinophils in the lamina propria (> 5 per highpower field), a linear disposition of T lymphocytes in the deeper mucosa, and small clusters of T lymphocytes 3⁄4 in the superficial epithelium which contained < 25 IEL on both H&E and CD3 stains [3]. Working on the assumption that some members of the non-celiac IELosis group may represent NCGS, we searched for the presence of the above features in our study. To our surprise, our controls, non-celiac IELosis, and type 1 celiac groups, all showed Blinear disposition of T lymphocytes in the deeper mucosa^ (Fig. 1a–c) on CD3 stain while some of the controls and non-celiac IELosis cases showed Bsmall clusters of T lymphocytes in the superficial epithelium^ (Fig. 1a, b depicted in circles) which was interpreted as Bfocal/uneven distribution^ in our paper [1]. In the duodenum, although still controversial, mucosal eosinophilia has been defined as > 22 eosinophils per 5 high-power fields at the base of crypts [4] which corresponds to Zanini’s definition of > 5 eosinophils per high-power field [3]. We find it difficult, however, to relate the eosinophilia specifically to NCGS, as it may result from various other conditions affecting the duodenal mucosa including celiac disease. We, therefore, believe that the defined histologic features of NCGS seem rather non-specific (some may even be considered as Bnormal^) and that, before confirmed by others, should not be attributed to a controversial and yet poorly defined entity. To support this view, we plan to extend our studies further to include NCGS cases and compare the histopathological features with those of controls, non-celiac IELosis, and type 1 celiac cases. No doubt, with further high-quality research like Zanini et al’s [3], it will be possible to improve our understanding of the morphologic spectrum of gluten-related disorders [5].