Contributions
Abstract: P544
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Biomarkers
Introduction: No specific marker of inflammation or neurodegeneration that can be used for prognostic purposes are currently available in Multiple Sclerosis (MS). Early and specific markers of local pathology should be identified in the cerebrospinal fluid (CSF).
Aim: To identify, among a wide spectrum of soluble molecules, CSF biomarkers associated with MRI parameters of white and grey matter damage at MS diagnosis and verify whether these biomarkers were predictive of clinical and radiological disease activity in the following 2 years.
Methods: At diagnosis, CSF examination, brain and spinal cord MRI (including 3D-T1, 3D-FLAIR and 3-DIR) and EDSS evaluation were performed. Multiplex technology (Bio-Plex Pro Human Cytokine, GF and Diabetes 27-Plex Panel, Bio-Plex Pro Human Chemokines 40-Plex Panel, Bio-Plex Pro Human Inflammation Assays 37-Plex Panel) was applied to analyse 87 cytokines in the CSF. Thereafter, clinical evaluation and MRI were performed biannually and annually, respectively, and EDSS changes, clinical relapses, evidence of new/enlarging white and grey matter lesions were scored.
Results: 51 Relapsing Remitting MS (RRMS) and 11 matched healthy controls (HC) were included the study. 11/87 molecules, namely CXCL13, CCL22, MIP-1α, CCL1, IL-16, CXCL11, CXCL10, CXCL6, CXCL9, CCL19, and CCL23, were increased in RRMS CSF compared to HC (p< 0.05 for all comparisons). Multivariate analysis disclosed that only MIP-1α (macrophage inflammatory chemokine) was associated with MS diagnosis (O.R.: 95.4, CI95% 1.9-4846.6, p=0.02). At baseline, grey matter lesion volume mildly correlated with IL-16 (r:0.41, p< 0.01) and global cortical thickness was inversely associated with both IL-26 (r:-0.34, p< 0.05) and CCL20 (r:-0.33, p< 0.05). No significant correlation was observed between white matter lesion volume and any cytokine. Based on the CI95% in HC (cut-off value: 0.707 pg/mL), MS patients were divided in RRMS-MIP1αhigh and RRMS-MIP1αlow. Survival analysis revealed that RRMS-MIP1αhigh had more frequently and earlier disease reactivation in the following two years compared to RRMS-MIP1αlow (OR 3.8, IC95% 1.3-11.0, p< 0.05). Finally, intrathecal IgG synthesis was inversely associated with CSF BAFF (p< 0.001) and directly associated with CCL23 (p=0.005) concentrations.
Conclusions: Our study points out a possible role of MIP1α, a chemokine intrathecally produced by astrocytes and acting as microglia activator, as candidate prognostic biomarkers for MS.
Disclosure: Puthenparampil Marco received travel grant from Novartis, Almirall, Genzyme, Biogen Idec, Teva and Sanofi Aventis; he has been consultant for Genzyme and Biogen Idec.
Stropparo Erica, Zywicki Sofia, Bovis Francesca, Cazzola Chiara, Poggiali Davide, and Maria Pia Sormani have nothing to disclose. Federle Lisa reports grants and personal fees from Novartis, grants and personal fees from Genzyme Sanofi, grants and personal fees from Biogen Italia, grants and personal fees from Almirall, grants and personal fees from Teva, grants and personal fees from Merck Serono, outside the submitted work. Miante Silvia reports grants from Novartis, grants from Genzyme Sanofi, grants from Biogen Italia, grants from Almirall, grants from Teva, grants from Merck Serono, outside the submitted work. Perini Paola has received funding for travel and speaker honoraria from Merck Serono, Biogen Idec, Sanofi-Aventis, and Bayer Schering Pharma and has been consultant for Merck Serono, Biogen Idec and Teva. Gallo Paolo has been a consultant for Bayer Schering, Biogen Idec, Genzyme, Merck Serono and Novartis; has received funding for travel and speaker honoraria from Merck-Serono, Biogen Idec, Sanofi-Aventis, Novartis Pharma and Bayer-Schering Pharma, Teva; has received research support from Bayer, Biogen Idec/Elan, MerkSerono, Genzyme and Teva; and has received research grant from the University of Padova, Veneto Region of Italy, the Italian Association for Multiple Sclerosis, the Italian Ministry of Public Health.
Abstract: P544
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Biomarkers
Introduction: No specific marker of inflammation or neurodegeneration that can be used for prognostic purposes are currently available in Multiple Sclerosis (MS). Early and specific markers of local pathology should be identified in the cerebrospinal fluid (CSF).
Aim: To identify, among a wide spectrum of soluble molecules, CSF biomarkers associated with MRI parameters of white and grey matter damage at MS diagnosis and verify whether these biomarkers were predictive of clinical and radiological disease activity in the following 2 years.
Methods: At diagnosis, CSF examination, brain and spinal cord MRI (including 3D-T1, 3D-FLAIR and 3-DIR) and EDSS evaluation were performed. Multiplex technology (Bio-Plex Pro Human Cytokine, GF and Diabetes 27-Plex Panel, Bio-Plex Pro Human Chemokines 40-Plex Panel, Bio-Plex Pro Human Inflammation Assays 37-Plex Panel) was applied to analyse 87 cytokines in the CSF. Thereafter, clinical evaluation and MRI were performed biannually and annually, respectively, and EDSS changes, clinical relapses, evidence of new/enlarging white and grey matter lesions were scored.
Results: 51 Relapsing Remitting MS (RRMS) and 11 matched healthy controls (HC) were included the study. 11/87 molecules, namely CXCL13, CCL22, MIP-1α, CCL1, IL-16, CXCL11, CXCL10, CXCL6, CXCL9, CCL19, and CCL23, were increased in RRMS CSF compared to HC (p< 0.05 for all comparisons). Multivariate analysis disclosed that only MIP-1α (macrophage inflammatory chemokine) was associated with MS diagnosis (O.R.: 95.4, CI95% 1.9-4846.6, p=0.02). At baseline, grey matter lesion volume mildly correlated with IL-16 (r:0.41, p< 0.01) and global cortical thickness was inversely associated with both IL-26 (r:-0.34, p< 0.05) and CCL20 (r:-0.33, p< 0.05). No significant correlation was observed between white matter lesion volume and any cytokine. Based on the CI95% in HC (cut-off value: 0.707 pg/mL), MS patients were divided in RRMS-MIP1αhigh and RRMS-MIP1αlow. Survival analysis revealed that RRMS-MIP1αhigh had more frequently and earlier disease reactivation in the following two years compared to RRMS-MIP1αlow (OR 3.8, IC95% 1.3-11.0, p< 0.05). Finally, intrathecal IgG synthesis was inversely associated with CSF BAFF (p< 0.001) and directly associated with CCL23 (p=0.005) concentrations.
Conclusions: Our study points out a possible role of MIP1α, a chemokine intrathecally produced by astrocytes and acting as microglia activator, as candidate prognostic biomarkers for MS.
Disclosure: Puthenparampil Marco received travel grant from Novartis, Almirall, Genzyme, Biogen Idec, Teva and Sanofi Aventis; he has been consultant for Genzyme and Biogen Idec.
Stropparo Erica, Zywicki Sofia, Bovis Francesca, Cazzola Chiara, Poggiali Davide, and Maria Pia Sormani have nothing to disclose. Federle Lisa reports grants and personal fees from Novartis, grants and personal fees from Genzyme Sanofi, grants and personal fees from Biogen Italia, grants and personal fees from Almirall, grants and personal fees from Teva, grants and personal fees from Merck Serono, outside the submitted work. Miante Silvia reports grants from Novartis, grants from Genzyme Sanofi, grants from Biogen Italia, grants from Almirall, grants from Teva, grants from Merck Serono, outside the submitted work. Perini Paola has received funding for travel and speaker honoraria from Merck Serono, Biogen Idec, Sanofi-Aventis, and Bayer Schering Pharma and has been consultant for Merck Serono, Biogen Idec and Teva. Gallo Paolo has been a consultant for Bayer Schering, Biogen Idec, Genzyme, Merck Serono and Novartis; has received funding for travel and speaker honoraria from Merck-Serono, Biogen Idec, Sanofi-Aventis, Novartis Pharma and Bayer-Schering Pharma, Teva; has received research support from Bayer, Biogen Idec/Elan, MerkSerono, Genzyme and Teva; and has received research grant from the University of Padova, Veneto Region of Italy, the Italian Association for Multiple Sclerosis, the Italian Ministry of Public Health.