Contributions
Abstract: P974
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - Immunology
Background: Intrathecal synthesis of lipid specific oligoclonal IgM Bands (LS-OCMB) predict an aggressive Multiple Sclerosis (MS) course. Our aim was to elucidate the immune mechanisms associated with the presence of these antibodies in MS patients and their changes with age.
Material and methods: 124 consecutive patients diagnosed with MS were included in this study. CSF and serum samples were collected. We analyzed oligoclonal IgG and IgM in the CSF by isoelectrofocusing and immunoblotting and studied different leukocyte subsets in CSF by flow cytometry.
Results: 43 (35%) patients had LS-OCMB+ restricted to CSF and the remaining 81 were LS-OCMB-. When analyzing cell percentages in CSF we found that LS-OCMB+ patients showed increased values of CD19 cells (p< 0.0001) and on regulatory CD4 T cells (p= 0.0009). Conversely, LS-OCMB- patients showed increased percentages of monocytes (p< 0.0001), mainly due to CD14hiCD16-(p< 0.0001) and CD14hiCD16+ (p< 0.0001) subsets. Also they had higher percentages of CD4 T cells producing IL-17 and IFN-gamma (p=0.04)
When studied absolute cell counts, we observed that LS-OCMB+ patients showed increased values in total B (p< 0.0001), CD4 (p=0.0015), CD8 (p=0.0014) populations. They also showed an increase of CD4 cells showing intracellular production of IFN-gamma (p=0.0007), TNF-alpha (p=0.0004). This association was also observed in CD8 cells.
No changes associated with age were found in leukocyte percentages and cells counts LSMB+ patients. Conversely LS-OCMB- ones showed and age associated decrease of total leukocyte counts (r=-0.43, p< 0.0001), decreasing total cell counts on CD4 (p< 0.0001), CD8 (p=0,0009) and B cells (p< 0,0001). Also the showed an age related decrease in B cell percentages (r=-0.34, p=0.0020) and an age-related increase of monocytes (r=0.26, p=0.02).
Conclusions: The presence of LS-OCM bands in MS is related to a high number of T cells producing inflammatory cytokines in CSF. Their absence associates with a lower number of B cells and an increased percentage of monocytes. These results suggest both groups of patients may have different disease mechanisms. Differences get more pronounced with age.
Disclosure: LM Villar received speaking honoraria from Bayer Schering Pharma, Merk Serono, Biogen-Idec, Teva Pharmaceuticals, Sanofi-Aventis, and Novartis; L Costa Frossard received speaking honoraria from Bayer Schering Pharma, Merk Serono, Biogen-Idec, Teva Pharmaceuticals, Sanofi-Aventis, and Novartis. JC Alvarez-Cermeño received speaking honoraria from Bayer Schering Pharma, Merk Serono, Biogen-Idec, Teva Pharmaceuticals, Sanofi-Aventis, and Novartis; S Sainz de la Maza received honoraria from Genzyme and Biogen; C Picón, Y Aladro, E Rodriguez-Martin, S Medina, have nothing to disclose.This project is supported by FIS PI12-00239 and SAF 2012-34670 projects from the Spanish Ministry of Economy and Competitivity.
Abstract: P974
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - Immunology
Background: Intrathecal synthesis of lipid specific oligoclonal IgM Bands (LS-OCMB) predict an aggressive Multiple Sclerosis (MS) course. Our aim was to elucidate the immune mechanisms associated with the presence of these antibodies in MS patients and their changes with age.
Material and methods: 124 consecutive patients diagnosed with MS were included in this study. CSF and serum samples were collected. We analyzed oligoclonal IgG and IgM in the CSF by isoelectrofocusing and immunoblotting and studied different leukocyte subsets in CSF by flow cytometry.
Results: 43 (35%) patients had LS-OCMB+ restricted to CSF and the remaining 81 were LS-OCMB-. When analyzing cell percentages in CSF we found that LS-OCMB+ patients showed increased values of CD19 cells (p< 0.0001) and on regulatory CD4 T cells (p= 0.0009). Conversely, LS-OCMB- patients showed increased percentages of monocytes (p< 0.0001), mainly due to CD14hiCD16-(p< 0.0001) and CD14hiCD16+ (p< 0.0001) subsets. Also they had higher percentages of CD4 T cells producing IL-17 and IFN-gamma (p=0.04)
When studied absolute cell counts, we observed that LS-OCMB+ patients showed increased values in total B (p< 0.0001), CD4 (p=0.0015), CD8 (p=0.0014) populations. They also showed an increase of CD4 cells showing intracellular production of IFN-gamma (p=0.0007), TNF-alpha (p=0.0004). This association was also observed in CD8 cells.
No changes associated with age were found in leukocyte percentages and cells counts LSMB+ patients. Conversely LS-OCMB- ones showed and age associated decrease of total leukocyte counts (r=-0.43, p< 0.0001), decreasing total cell counts on CD4 (p< 0.0001), CD8 (p=0,0009) and B cells (p< 0,0001). Also the showed an age related decrease in B cell percentages (r=-0.34, p=0.0020) and an age-related increase of monocytes (r=0.26, p=0.02).
Conclusions: The presence of LS-OCM bands in MS is related to a high number of T cells producing inflammatory cytokines in CSF. Their absence associates with a lower number of B cells and an increased percentage of monocytes. These results suggest both groups of patients may have different disease mechanisms. Differences get more pronounced with age.
Disclosure: LM Villar received speaking honoraria from Bayer Schering Pharma, Merk Serono, Biogen-Idec, Teva Pharmaceuticals, Sanofi-Aventis, and Novartis; L Costa Frossard received speaking honoraria from Bayer Schering Pharma, Merk Serono, Biogen-Idec, Teva Pharmaceuticals, Sanofi-Aventis, and Novartis. JC Alvarez-Cermeño received speaking honoraria from Bayer Schering Pharma, Merk Serono, Biogen-Idec, Teva Pharmaceuticals, Sanofi-Aventis, and Novartis; S Sainz de la Maza received honoraria from Genzyme and Biogen; C Picón, Y Aladro, E Rodriguez-Martin, S Medina, have nothing to disclose.This project is supported by FIS PI12-00239 and SAF 2012-34670 projects from the Spanish Ministry of Economy and Competitivity.