Background: Eosinophilic esophagitis (EoE) is a recently defined chronic immune-mediated disease of atopic etiology with esophageal dysfunction and mucosal eosinophilic infiltrate. Among esophageal high-resolution manometry (HRM) parameters, intrabolus pressure (IBP) has shown the possibility to distinguish patients with mucosal inflammation, who benefit from proton pump inhibitors (PPI), from those with initial fibrosis and lack of response to treatment. In this study, we aimed to identify biomarkers able to identify which group a patient belongs to and obtain an early response. Methods: Combining diagnostic and esophageal function tests, proteomic and histological immunohistochemical analysis we studied 24 patients with EoE to extrapolate a protein profile from biopsies of the middle third of the esophagus analysis. Among them, 20 patients also underwent esophageal HRM. Results: IBP values were found to be significantly different among the controls, responsive and non-responsive patients, in relation to PPI treatment. Proteomic analysis identified 1,445 proteins, 456 shared between the two groups of patients, with 58 proteins identified as differentially expressed (DEPs) between the two groups of patients. Among all identified proteins, we found that, by immunohistochemistry, Gal-3 was overexpressed in patients’ responder to PPI, and with image analysis the difference between the two groups was statistically significant (% positive cells p<0.01, % positive area p<0.005) Conclusions: This study showed the chance of knowing forward the response to PPI therapy, improving patients’ personalized therapy and quality of life.

Background: Increasing evidence are available about the presence of increased serum concentration of Immunoglobulin (Ig) Free Light Chains (FLCs) in both atopic and non-atopic inflammatory diseases, including severe asthma, providing a possible new biomarker of disease, disease severity and also an alternative approach to the treatment. Methods: We analyzed clinical and laboratory data, including FLCs, obtained from a cohort of 79 asthmatic subjects, clinically classified into different GINA steps. A control group of 40 age-matched healthy donors (HD) was considered. Particularly, HD have been selected according to the absence of monoclonal components (in order to exclude paraproteinemias), were tested for total IgE (that were in the normal ranges) and were negative for aeroallergens specific IgE. Moreover, no abnormality of common inflammatory markers (i.e. erythrocyte sedimentation rate, C-reactive protein) was detectable. Results: FLC-k levels were significantly increased in the asthmatic population, compared to the control group. Despite the absence of statistically significant differences in FLC-λ levels, the FLC-k/FLC-λ ratio displayed remarkable differences between the two groups. A positive correlation between FLC-κ and FLC-λ levels was found. FLC- λ level displayed a significant negative correlation with the FEV1 value. Moreover, the FLC-κ /FLC- λ ratio was negatively correlated with the SNOT-22 score and a positive correlation was observed between FLCs and Staphylococcus Aureus IgE enterotoxins sensitization. Conclusions: Our findings confirmed the role of FLCs in asthma as a potential biomarker in an inflammatory disease characterized by different endotypes and phenotypes. In particular, FLC-κ and FLC-k/FLC-λ ratio could be a qualitative indicator for asthma, while FLC-λ levels could be a quantitative indicator for disease severity.