Contributions
Abstract: EP1562
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Biomarkers
Introduction: Up to now diagnosis of primary progressive multiple sclerosis (PPMS) is based on clinical assessment, imaging and cerebrospinal fluid (CSF) analysis with regard to evidence of oligoclonal bands and/or elevated IgG index. However, specific biomarkers that can help to early stratify PPMS from relapsing remitting multiple sclerosis (RRMS) patients and give insights into its pathogenesis are still unknown.
Aims: To identify a specific CSF inflammatory profile associated to PPMS since early phases of disease.
Methods: An extensive analysis of the presence and levels of 69 inflammatory mediators (cytokines and chemokines) and NF-L has been performed on the CSF obtained at the diagnosis from 14 patients (mean age 45.9±9.4 y) with PPMS, 45 (32.4±9.6 y) with RRMS, 7 (37.7±12.1 y) with Clinically Isolated Syndrome (CIS) and 12 (51.7±12.1 y) with non-inflammatory neurological disorders. Data about white and grey matter (WM, GM) lesion volume and cortical lesion (CL) numbers were collected by 3T-MRI.
Results: No significant differences between PPMS and RRMS patients were noticed in IgG index, oligoclonal bands, CSF lymphocyte count, NF-L levels, CL numbers, WM and GM lesion volume. PPMS had higher mean EDSS respect to RRMS group (3.0 vs 1.7, p< 0.01). Interestingly, CSF of PPMS patients was characterized by a pattern of inflammatory molecules, including CCL11, CCL26, CX3CL1, CXCL2, CCL2, CCL7, CCL15, CCL23, IL-16, significantly overexpressed when compared to RRMS and control group (p< 0.05); among them, CCL2 and CCL15 were found significantly increased also when compared to CIS group (p < 0.05). Higher levels of CXCL13, IL28A and Pentraxin were detected in RRMS compared to PPMS, control group and, except IL28A, CIS patients (p< 0.01). Kegg pathway analysis confirmed that most of molecules characterizing PPMS CSF profile are specifically involved in immune reactions observed in other chronic inflammatory diseases.
Conclusions: At the diagnosis CSF of PPMS patients showed a specific pattern, involved in chronic inflammation: while CXCL13, Pentraxin and IL28A may represent surrogate markers of a relapsing disease, CCL2 and CCL15 should be better assessed as potential PPMS biomarkers. In addition to clinical and instrumental analysis, a detailed CSF profiling obtained at the diagnosis could help to differentiate progressive forms of MS, giving new insights into its pathogenesis and providing useful tools in clinical practice.
Disclosure: Massimiliano Calabrese received honoraria for reasearch or speaking from Sanofi-Genzyme, Merck-Serono, Biogen Idec, Bayer, Novartis Pharma and funds for travel from Sanofi-Genzyme, Merck-Serono, Biogen Idec, Teva, Novartis Pharma, Roche and Bayer.
D. Marastoni: nothing to disclose.
R. Magliozzi: nothing to disclose.
S. Rossi: nothing to disclose.
S. Monaco: nothing to disclose.
Abstract: EP1562
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Biomarkers
Introduction: Up to now diagnosis of primary progressive multiple sclerosis (PPMS) is based on clinical assessment, imaging and cerebrospinal fluid (CSF) analysis with regard to evidence of oligoclonal bands and/or elevated IgG index. However, specific biomarkers that can help to early stratify PPMS from relapsing remitting multiple sclerosis (RRMS) patients and give insights into its pathogenesis are still unknown.
Aims: To identify a specific CSF inflammatory profile associated to PPMS since early phases of disease.
Methods: An extensive analysis of the presence and levels of 69 inflammatory mediators (cytokines and chemokines) and NF-L has been performed on the CSF obtained at the diagnosis from 14 patients (mean age 45.9±9.4 y) with PPMS, 45 (32.4±9.6 y) with RRMS, 7 (37.7±12.1 y) with Clinically Isolated Syndrome (CIS) and 12 (51.7±12.1 y) with non-inflammatory neurological disorders. Data about white and grey matter (WM, GM) lesion volume and cortical lesion (CL) numbers were collected by 3T-MRI.
Results: No significant differences between PPMS and RRMS patients were noticed in IgG index, oligoclonal bands, CSF lymphocyte count, NF-L levels, CL numbers, WM and GM lesion volume. PPMS had higher mean EDSS respect to RRMS group (3.0 vs 1.7, p< 0.01). Interestingly, CSF of PPMS patients was characterized by a pattern of inflammatory molecules, including CCL11, CCL26, CX3CL1, CXCL2, CCL2, CCL7, CCL15, CCL23, IL-16, significantly overexpressed when compared to RRMS and control group (p< 0.05); among them, CCL2 and CCL15 were found significantly increased also when compared to CIS group (p < 0.05). Higher levels of CXCL13, IL28A and Pentraxin were detected in RRMS compared to PPMS, control group and, except IL28A, CIS patients (p< 0.01). Kegg pathway analysis confirmed that most of molecules characterizing PPMS CSF profile are specifically involved in immune reactions observed in other chronic inflammatory diseases.
Conclusions: At the diagnosis CSF of PPMS patients showed a specific pattern, involved in chronic inflammation: while CXCL13, Pentraxin and IL28A may represent surrogate markers of a relapsing disease, CCL2 and CCL15 should be better assessed as potential PPMS biomarkers. In addition to clinical and instrumental analysis, a detailed CSF profiling obtained at the diagnosis could help to differentiate progressive forms of MS, giving new insights into its pathogenesis and providing useful tools in clinical practice.
Disclosure: Massimiliano Calabrese received honoraria for reasearch or speaking from Sanofi-Genzyme, Merck-Serono, Biogen Idec, Bayer, Novartis Pharma and funds for travel from Sanofi-Genzyme, Merck-Serono, Biogen Idec, Teva, Novartis Pharma, Roche and Bayer.
D. Marastoni: nothing to disclose.
R. Magliozzi: nothing to disclose.
S. Rossi: nothing to disclose.
S. Monaco: nothing to disclose.