Aim: In our study we explored a possible relationship between PTX3 and CD. Background: Gluten sensitivity is known as a hallmark of celiac disease (CD). The diagnosis of CD requires demonstration of a typical enteropathy, and positive serology supports the diagnosis. The CD immune response involves the adaptive, as well as the innate immunity and is characterized by the presence of anti-gliadin (AGA) and anti-transglutaminase 2 antibodies (tTGA), lymphocytic infiltration in the intestinal epithelial membrane and expression of multiple cytokines. The long pentraxin 3 (PTX3), an acute-phase inflammatory molecule, plays an important role in innate immunity. Methods: 108 CD patients were divided according to Marsh Histological grade following Marsh criteria classification in three groups: Group 1: Marsh 0, patients with a known history of CD under gluten free diet, complete remission; Group 2: Marsh1 and Marsh 2; Group 3: Marsh 3. Healthy age-matched controls without a known history of CD or gastrointestinal symptoms (n=30) served as controls. PTX3 serum levels were measured by sandwich ELISA on an automated platform. Results: PTX3 serum levels were significantly elevated in group 3 and group 2 compared with HC (mean 3. 31± 1. 27 ng/mL and 3. 97 ± 0. 54 ng/mL versus 1. 06 ± 0. 59 ng/mL; P < 0. 005), with group 1 (0. 76± 0. 31 ng/mL). No statistically significant differences were found between group 1 and HC group. We found a strong linear correlation between PTX3 serum levels and AGA levels in group 2 (r=0. 78, P <0. 0001), and group 3 (r =0. 63, P < 0. 005) but no correlations were detected between PTX3 serum levels and tTGA levels (group 2, r= 0. 04; group 3, r=0. 24). Serological data revealed that PTX3 correlated with major gastrointestinal damage patients. Conclusion: PTX3 is a component of the humoral arm of the innate immune system. Our data showed that PTX3 serum levels were high in active disease patients with pathological levels of AGA. We also demonstrated that patients with normal AGA IgA levels had PTX3 serum levels compared to healthy control. We hypothesized that PTX3 is able to modulate the innate response to gliadin in CD and it could regulate the adaptive immune response.