Contributions
Abstract: P653
Type: Poster
Abstract Category: Therapy - disease modifying - 26 Immunomodulation/Immunosuppression
Objective: The study the effect of immunization against CCL20 in EAE and MS.
Background: Th-17 type immune response was implicated in the pathogenesis of MS and is linked to chemokine receptor CCR6 and its ligand CCL20. The CCR6-CCL20 axis was found to be important in introduction of inflammation into the CNS via the choroid plexus.
Design and methods: EAE was induces with MOG35-55 in C57BL/6 mice, in CCR6 -/- mice, in mice that were pre-immunized with hCCL20 or were adoptively transferred with sera from immunized mice with hCCL20 and the severity of EAE was studied. Production of anti-CCL20 was induced by immunization of Balbc/c mice against CCL20. Levels of anti- CCL20 studied in sera of MS patients and healthy controls (HC) - tested by ELISA.
Results: EAE severity was reduced by up to 70% with a significantly reduced accumulating score (AS) in CCR6-/- mice with EAE vs. wild type mice with EAE (p< 0.001). Vaccinating of mice with human CCL20, but not with mouse CCL20, produced autoantibodies against murine CCL20, and protects mice against MOG35-55 induced EAE (AS = 2.2 vs. 89.6, p< 0.001). Protective effect was I.V adoptively transferred with sera from hCCL20 immunized mice to non-immunized mice (AS=36.8, p=0.019). Anti mCCL20 levels were negatively correlated with degree EAE severity (R2=0.7667). Using bioinformatics search, we identified a novel peptide sequence - LGYTDRI, comprising an epitope conserved among bacterial capsular outer membrane protein A (ompA) containing homologic sequence with hCCL20. Pre-immunization with ompA or with the LGYTDRI peptide ameliorated EAE vs. control EAE (AS=25.2 and 31.2 vs. 42.9; p=0.03 and 0.04, respectively). We found a significantly lower levels of anti CCL20 in sera of 103 relapsing remitting MS patients (0.22±0.03 O.D405) vs. 44 matched HC (0.43±0.08 O.D405, p=0.016).
Conclusions: Naturally or induction blockade of CCL20 may confer protection against autoimmune disease such as MS, probably by preventing the trafficking of Th17 CCR6+ cells to the central nervous system. Active or passive immunization against CCL20 may confer protection against MS.
Disclosure:
Dr. Karni, Dr. Abraham, Dr. Fainberg, Dr. Weiss and Dr, Peled have noting to disclose.
Abstract: P653
Type: Poster
Abstract Category: Therapy - disease modifying - 26 Immunomodulation/Immunosuppression
Objective: The study the effect of immunization against CCL20 in EAE and MS.
Background: Th-17 type immune response was implicated in the pathogenesis of MS and is linked to chemokine receptor CCR6 and its ligand CCL20. The CCR6-CCL20 axis was found to be important in introduction of inflammation into the CNS via the choroid plexus.
Design and methods: EAE was induces with MOG35-55 in C57BL/6 mice, in CCR6 -/- mice, in mice that were pre-immunized with hCCL20 or were adoptively transferred with sera from immunized mice with hCCL20 and the severity of EAE was studied. Production of anti-CCL20 was induced by immunization of Balbc/c mice against CCL20. Levels of anti- CCL20 studied in sera of MS patients and healthy controls (HC) - tested by ELISA.
Results: EAE severity was reduced by up to 70% with a significantly reduced accumulating score (AS) in CCR6-/- mice with EAE vs. wild type mice with EAE (p< 0.001). Vaccinating of mice with human CCL20, but not with mouse CCL20, produced autoantibodies against murine CCL20, and protects mice against MOG35-55 induced EAE (AS = 2.2 vs. 89.6, p< 0.001). Protective effect was I.V adoptively transferred with sera from hCCL20 immunized mice to non-immunized mice (AS=36.8, p=0.019). Anti mCCL20 levels were negatively correlated with degree EAE severity (R2=0.7667). Using bioinformatics search, we identified a novel peptide sequence - LGYTDRI, comprising an epitope conserved among bacterial capsular outer membrane protein A (ompA) containing homologic sequence with hCCL20. Pre-immunization with ompA or with the LGYTDRI peptide ameliorated EAE vs. control EAE (AS=25.2 and 31.2 vs. 42.9; p=0.03 and 0.04, respectively). We found a significantly lower levels of anti CCL20 in sera of 103 relapsing remitting MS patients (0.22±0.03 O.D405) vs. 44 matched HC (0.43±0.08 O.D405, p=0.016).
Conclusions: Naturally or induction blockade of CCL20 may confer protection against autoimmune disease such as MS, probably by preventing the trafficking of Th17 CCR6+ cells to the central nervous system. Active or passive immunization against CCL20 may confer protection against MS.
Disclosure:
Dr. Karni, Dr. Abraham, Dr. Fainberg, Dr. Weiss and Dr, Peled have noting to disclose.