Contributions
Abstract: P850
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Biomarkers
Background: Neuro-axonal loss and gliotic scar formation represent key pathological features in multiple sclerosis (MS). Neurofilaments provide information on neuro-axonal integrity. Glial fibrillary acidic protein (GFAP) is a specifically astrocytic protein, whose levels reflect astrogliosis. Ultrasensitive Single Molecule Array (Simoa) assays now allow reliable quantification of GFAP in peripheral blood.
Objectives: To study the association of GFAP in the cerebrospinal fluid and paired plasma samples (pGFAP) and characterize the factors associated with increased levels in different stages of MS.
Methods: We analyzed i) CSF samples (n=154) from 66 relapsing remitting MS (RRMS), 21 secondary progressive MS (SPMS), 14 primary progressive MS (PPMS) and 53 controls (non-inflammatory neurologic disease); ii) plasma samples (n=221) from 76 RRMS, 51 SPMS, 41 PPMS and 53 controls. GFAP was measured by a commercially available Simoa assay.
Analysis was performed by multivariable linear regression models and Spearman's rank correlation.
Results: Paired plasma and CSF GFAP levels were highly correlated (rs=0.59, p< 0.001). pGFAP levels were higher in RRMS, SPMS and PPMS than in controls (p< 0.001, after age correction), but there was no significant difference between disease stages. A longer disease duration, but not age, was associated with increasing pGFAP (β=1.013, p=0.010). Similarly, a 1 point higher EDSS score was associated with an average increase of 10.4% in pGFAP (β=1.104, p< 0.001). Relapse activity (within 120 days from sampling) did not influence pGFAP levels.
Conclusion: Highly sensitive GFAP measurements in blood may complement neurofilament detection as measure of chronic astrogliosis and disease burden. The association between CSF and plasma GFAP levels supports the value of plasma measurements. Higher pGFAP levels with longer disease duration, but not with acute relapse activity, are in line with the concept of accumulating astrogliosis especially in the progressive stages of the disease. Future studies need to further characterise the temporal profile of pGFAP, its responsiveness to treatment and possible potential as a tool to predict disease progression in MS.
Disclosure: CB received travel support by Teva and Novartis not related to this work.
PB, ,SG, ZM report no disclosures.
LK's institution (University Hospital Basel) has received in the last 3 years and used exclusively for research support: Steering committee, advisory board, and consultancy fees from Actelion, Addex, Bayer HealthCare, Biogen Idec, Biotica, Genzyme, Lilly, Merck, Mitsubishi, Novartis, Ono Pharma, Pfizer, Receptos, Sanofi, Santhera, Siemens, Teva, UCB, and Xenoport; speaker fees from Bayer HealthCare, Biogen Idec, Merck, Novartis, Sanofi, and Teva; support of educational activities from Bayer HealthCare, Biogen, CSL Behring, Genzyme, Merck, Novartis, Sanofi, and Teva; license fees for Neurostatus products; and grants from Bayer HealthCare, Biogen Idec, European Union, Merck, Novartis, Roche Research Foundation, Swiss MS Society, and the Swiss National Research Foundation.
JK's institution (University Hospital Basel) received and used exclusively for research support: consulting fees from Biogen, Novartis, Protagen AG, Roche, Teva; speaker fees from the Swiss MS Society, Biogen, Novartis, Roche, Genzyme; travel expenses from Merck Serono, Novartis, Roche; grants from ECTRIMS Research Fellowship Programme, University of Basel, Swiss MS Society, Swiss National Research Foundation (320030_160221), Bayer AG, Biogen, Genzyme, Merck, Novartis, Roche.
Abstract: P850
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Biomarkers
Background: Neuro-axonal loss and gliotic scar formation represent key pathological features in multiple sclerosis (MS). Neurofilaments provide information on neuro-axonal integrity. Glial fibrillary acidic protein (GFAP) is a specifically astrocytic protein, whose levels reflect astrogliosis. Ultrasensitive Single Molecule Array (Simoa) assays now allow reliable quantification of GFAP in peripheral blood.
Objectives: To study the association of GFAP in the cerebrospinal fluid and paired plasma samples (pGFAP) and characterize the factors associated with increased levels in different stages of MS.
Methods: We analyzed i) CSF samples (n=154) from 66 relapsing remitting MS (RRMS), 21 secondary progressive MS (SPMS), 14 primary progressive MS (PPMS) and 53 controls (non-inflammatory neurologic disease); ii) plasma samples (n=221) from 76 RRMS, 51 SPMS, 41 PPMS and 53 controls. GFAP was measured by a commercially available Simoa assay.
Analysis was performed by multivariable linear regression models and Spearman's rank correlation.
Results: Paired plasma and CSF GFAP levels were highly correlated (rs=0.59, p< 0.001). pGFAP levels were higher in RRMS, SPMS and PPMS than in controls (p< 0.001, after age correction), but there was no significant difference between disease stages. A longer disease duration, but not age, was associated with increasing pGFAP (β=1.013, p=0.010). Similarly, a 1 point higher EDSS score was associated with an average increase of 10.4% in pGFAP (β=1.104, p< 0.001). Relapse activity (within 120 days from sampling) did not influence pGFAP levels.
Conclusion: Highly sensitive GFAP measurements in blood may complement neurofilament detection as measure of chronic astrogliosis and disease burden. The association between CSF and plasma GFAP levels supports the value of plasma measurements. Higher pGFAP levels with longer disease duration, but not with acute relapse activity, are in line with the concept of accumulating astrogliosis especially in the progressive stages of the disease. Future studies need to further characterise the temporal profile of pGFAP, its responsiveness to treatment and possible potential as a tool to predict disease progression in MS.
Disclosure: CB received travel support by Teva and Novartis not related to this work.
PB, ,SG, ZM report no disclosures.
LK's institution (University Hospital Basel) has received in the last 3 years and used exclusively for research support: Steering committee, advisory board, and consultancy fees from Actelion, Addex, Bayer HealthCare, Biogen Idec, Biotica, Genzyme, Lilly, Merck, Mitsubishi, Novartis, Ono Pharma, Pfizer, Receptos, Sanofi, Santhera, Siemens, Teva, UCB, and Xenoport; speaker fees from Bayer HealthCare, Biogen Idec, Merck, Novartis, Sanofi, and Teva; support of educational activities from Bayer HealthCare, Biogen, CSL Behring, Genzyme, Merck, Novartis, Sanofi, and Teva; license fees for Neurostatus products; and grants from Bayer HealthCare, Biogen Idec, European Union, Merck, Novartis, Roche Research Foundation, Swiss MS Society, and the Swiss National Research Foundation.
JK's institution (University Hospital Basel) received and used exclusively for research support: consulting fees from Biogen, Novartis, Protagen AG, Roche, Teva; speaker fees from the Swiss MS Society, Biogen, Novartis, Roche, Genzyme; travel expenses from Merck Serono, Novartis, Roche; grants from ECTRIMS Research Fellowship Programme, University of Basel, Swiss MS Society, Swiss National Research Foundation (320030_160221), Bayer AG, Biogen, Genzyme, Merck, Novartis, Roche.