All 227 individuals were characterized for histopathology, anti-TG2, EMA, HLA typing, and AAA-IgA. Table 1 Prevalence of the symptoms suggestive of CD in our retrospective (149 CD patients) and prospective (50 CD patients) studies. value 0.05 was considered significant. 3. We confirm that algorithm-1 may avoid the duodenal biopsy in many CD patients and underscores the usefulness of AAA-IgA in reducing the number of duodenal biopsies in patients with moderate BCOR anti-TG2 levels. 1. Introduction Coeliac disease (CD) is an immune-mediated systemic disease, brought on and maintained by dietary gluten in genetically predisposed individuals, characterized by a variable small intestinal villous damage and by different clinical manifestations [1]. Recently, a synopsis summarizing some of the evidence statements and recommendations of the guidelines in CD diagnosis for use in clinical practice has been formulated by a working group within the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) [2]. An important statement of these guidelines is the development of two new algorithms for CD diagnosis based on (i) the presence of symptoms and indicators suggestive of CD in children and adolescents (algorithm-1) and (ii) the absence of symptoms and indicators in persons at genetic risk for developing CD (algorithm-2). We have considered in the present work the most interesting of the two new algorithms, algorithm-1. It allows diagnosis of CD without performing the duodenal biopsy in children and adolescents with symptoms and indicators suggestive of CD, anti-transglutaminase NM107 type 2 antibody (anti-TG2) levels 10 occasions upper limit of normal (ULN), and positive confirmation assessments of anti-endomysium-IgA antibodies (EMA) and with the presence of at-risk HLA-DQ2 or -DQ8. If all these requirements are fulfilled, the diagnosis of CD is confirmed, gluten-free diet is usually started, and the patient is usually studied for improvement of symptoms and decline of autoantibodies. A later gluten challenge in these patients is not required [2]. However, it has been established that symptomatic CD patients with elevated degrees of intestinal damage may also have anti-TG2 levels lower than 10 occasions ULN [3, 4]. Therefore, a high number of symptomatic CD patients with anti-TG2 levels lower than 10 occasions ULN, and to whom algorithm-1 cannot be applied, still necessitate a duodenal biopsy. Since anti-actin IgA antibodies (AAA-IgA) directed against actin filaments are strongly correlated with total or subtotal intestinal atrophy [5, 6], we hypothesized that serum measurement of this autoantibody may contribute in increasing the number of patients who can avoid a duodenal biopsy. Aims of this study were (i) to evaluate retrospectively in 227 individuals (149 CD patients and 78 controls) the performance of algorithm-1, (ii) to reduce further the number of NM107 duodenal biopsies among CD patients in whom NM107 algorithm-1 cannot be applied NM107 with the addition of AAA-IgA, and (iii) to evaluate also prospectively the performance of algorithm-1 combined with AAA-IgA levels in 50 individuals with symptoms suggestive of CD. 2. Material and Methods 2.1. Patients Our group consisted of 163 consecutive Sardinian CD patients (121 females, 42 males, ratio females/males 2.9, mean age at diagnosis 8 years, and range from 2 to 18 years); 149 presented symptoms suggestive of CD (Table 1), whilst 11 were not included in the study because they were asymptomatic and, for this reason, not belonging to the algorithm-1. Also, three patients with IgA deficiency, a well-known condition complicating the interpretation of the serological pattern of CD, were excluded. All patients were diagnosed according to ESPGHAN criteria [7] and were recruited from subjects attending the ambulatory of the Pediatric Gastroenterological Unit in Cagliari, Italy, between 2005 and 2012. A further group of 78 individuals with persistent significant gastrointestinal symptoms, already characterized by upper digestive endoscopy and small bowel biopsy [6], were used as non-CD subjects. All 227 individuals were characterized for histopathology, anti-TG2, EMA, HLA typing, and AAA-IgA. Table 1 Prevalence of the symptoms suggestive of CD in our retrospective (149 CD patients) and prospective (50 CD patients) studies. value 0.05 was considered significant. 3. Results The one hundred and forty-nine CD patients and 78 controls were classified in 3 different Subgroups.