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.

Autoimmune hepatitis with eosinophilic infiltration responsive to anti IL-5 Receptor treatment: a case report and literature reviewPonziani Francesca Romana *1, Caruso Cristiano*2, Baglivo Ilaria3°, Macagno Francesco4, Gasbarrini Antonio3, Santopaolo Francesco1, Giustiniani Maria Cristina5, Colantuono Stefania2 and Pompili Maurizio1Division of Internal Medicine and Gastroenterology, Hepatology Unit, Fondazione Policlinico Universitario ”A. Gemelli” IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy.UOSD DH Internal Medicine and Gastroenterology, Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario ”A. Gemelli” IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy.CEMAD Digestive Diseases Center, Fondazione Policlinico Universitario ”A. Gemelli” IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy.Complex Operational Unit of Pulmonology, Fondazione Policlinico Universitario ”A. Gemelli” IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy.Faculty of Medicine and Surgery, Institute of Pathological Anatomy, Fondazione Policlinico Universitario ”A. Gemelli” IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy.* these authors equally contributed° corresponding author

Background: Eosinophilic asthma (EA) is characterized by abnormal production and release of type 2 cytokines, such as interleukin-5 (IL-5), from T helper type 2 (Th2) lymphocytes and type 2 innate lymphoid cells (1). The aim of this study was to evaluate the usefulness of the basophil phenotype assessment and serum IL-5 assay in monitoring a series of severe EA patients treated with anti IL-5 drugs and correlate the results of these tests with baseline patients’ characteristics and clinical response, with particular attention to systemic steroid use and asthma exacerbations. Methods: Blood samples of 19 severe asthma patients were collected at T3 and T6 for evaluation of serum levels of IL-5 and basophil phenotype assessment. Results: All patients experienced an improvement of lung function, with an increase of FEV1 from a mean value of 71.9 to 83.8% of the theoretical value (+12%). Oral corticosteroids were progressively reduced and finally stopped in 14 (73.7%) of the 19 patients after six months of follow-up. Patients who achieved a complete response to anti-IL5 treatment showed a rate of activated basophils CD3negCRTH2posCD203cposCD125pos (4.78 ± 2.26%) at T0 significantly lower than that of patients not achieving the complete response (34.57 ± 14.01%, p=0.05). Conclusions: This pilot study in EA patients shows that the determination of activated basophils, that express CD125 is related to anti IL5/IL5Rα drug mechanism of action and subsequent immune response, proving to be a biomarker that identifies the patient’s phenotype that responds to therapy and that requires the concomitant use of OCS.