Increased IL-10-producing B-lymphocytes in the Peripheral Blood of Neuromyelitis Optica Treated Patients (P5.305)

2016 
Objective: To investigate the IL10-producing B-cells regulatory function in NMO patients compared to controls. Introduction: Neuromyelitis optica (NMO) is an inflammatory autoimmune neurologic disease associated with antibodies to aquaporin-4. Among B-lymphocytes sub-populations, IL-10-producing B-cells act regulating immune-function through IL-10 secretion, which can suppress cells activation, cytokine production, and antigen presentation. IL-27 induces IL-10 producing regulatory T-cells (Tr1) and acts as negative feedback mechanism against Th17 immune-response. Material and methods. Twelve patients (10 females, 2 males; mean age 32.1± 9.3 years old) in immunosuppressive therapy with NMO diagnosed according to Wingerchuk’s revised 2006 criteria were enrolled in the study. PBMCs were FACS stained for phenotypic studies. B-cells were sorted by magnetic beads, 24h-stimulated in different conditions and total RNA extracted for gene expression RT-qPCR studies. Cytokine expression was analyzed at supernatants by ELISA. Results: We demonstrated significant increase in IL-10-producing B-cells in ODN-CpG-stimulated PBMC in NMO compared to controls. In addition, IL-27-mRNA was significant increased, associated with decreased IL-17-mRNA expression. However, supernatants IL-17 levels increased significantly in NMO samples after priming PBMCs with anti-CD3/anti-D28 stimulation. Furthermore, we detected 40-50[percnt] of B-cells expressing IL27-receptor, which suggested that IL-27 may exert its effect in inducing IL-10 producing B-lymphocytes. Although IL-10 was also involved in the generation of antibody, we cannot ruled out the possibility of the treatment is inducing these regulatory mechanism in NMO. Conclusion: Our results suggests that the increased IL-10-producing B-cells subpopulation in NMO could be related to the increased production of IL-27 and decreased expression of IL-17 in the peripheral blood cells compared to healthy controls. Financial support: FAPESP, CAPES e CNPq Disclosure: Dr. Rafael has nothing to disclose. Dr. Dionete has nothing to disclose. Dr. Moraes has nothing to disclose. Dr. Andrade has nothing to disclose. Dr. Boldrini has nothing to disclose. Dr. Longhini has nothing to disclose. Dr. Damasceno has nothing to disclose. Dr. Damasceno has nothing to disclose. Dr. Pradella has nothing to disclose. Dr. Farias has nothing to disclose. Dr. Tilbery has nothing to disclose. Dr. Brandao has nothing to disclose. Dr. Gandhi has received personal compensation for activities with Biogen and Novartis. Dr. Santos has nothing to disclose. Dr. Von Glehn Silva has nothing to disclose.
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