Contributions
Abstract: 213
Type: Scientific Session
Abstract Category: Pathology and pathogenesis of MS - Biomarkers
Introduction: Glial fibrillary acidic protein (GFAP) is an astrocytic protein with known increased CSF concentrations in neuromyelitis optica spectrum disorders (NMOSD). Neurofilament light chain (NfL) is an exclusively neuronal protein that has been shown to be a measure of disease activity and short- and longer term disability progression in multiple sclerosis (MS). It remains to be established whether serum GFAP (sGFAP) and NfL (sNfL) are associated with disease activity or worsening in NMOSD.
Objectives: To investigate whether sGFAP and sNfL levels are related to disease activity and disability in NMOSD and MS patients.
Methods: GFAP and NfL levels in CSF and sera were measured in healthy controls (HC, n = 49; 49 sera), NMOSD (n = 34; 43 CSF and 104 sera) and MS patients (n = 49; 53 CSF and 91 sera) by using a homebrew and commercially available ultrasensitive single-molecule array (Simoa) assay, respectively. The relation of sNfL and sGFAP levels to clinical parameters was assessed.
Results: We found a strong association between CSF and serum GFAP levels (NMOSD, r = 0.963, p < 0.0001; MS, r = 0.690, p < 0.0001) and between CSF and serum NfL levels (NMOSD, r = 0.746, p < 0.0001; MS, r = 0.842, p < 0.0001). sGFAP levels were correlated with age in HC, but not in NMOSD nor MS (p = 0.0087, 0.68, 0.91, respectively). sGFAP and sNfL levels were higher in NMOSD patients than in HC (p < 0.0001, both). Moreover, sGFAP levels in NMOSD were higher than those in MS patients (median: 199.4 versus 121.1 pg/ml, p < 0.0001). In NMOSD, sGFAP levels in acute relapse were higher than in remission (634.7 versus 141.6 pg/ml, p < 0.0001). sGFAP levels were associated with Expanded Disability Status Scale (EDSS) scores in MS patients.
Conclusions: Highly sensitive detection now allows reliable quantification of GFAP in blood samples from patients with NMOSD. These results suggest that besides sNfL, longitudinal GFAP level determinations in blood have the future potential to inform about disease activity and optimal treatment response in NMOSD.
Disclosure: Mitsuru Watanabe has received grant support from Japan Society for the Promotion of Science (JSPS KAKENHI Grant Number 17K16124) and GlaxoSmithKline.
Yuri Nakamura has received a grant and salary from Mitsubishi Tanabe Pharma, Bayer Yakuhin, Ltd., and Japan Blood Products Organization.
Zuzanna Michalak: nothing to disclose.
Fumie Hayashi: nothing to disclose.
Christian Barro has received travel support from Teva and Novartis.
Noriko Isobe has received grant support from JSPS KAKENHI 18K07529, Japan Intractable Disease Research Foundation, Mitsubishi Tanabe Pharma, Bayer Yakuhin, Ltd., and Japan Blood Products Organization.
Takuya Matsushita has received speaker honoraria payments from Mitsubishi Tanabe Pharma, Takeda Pharmaceutical Company and Biogen Japan.
Ryo Yamasaki has received grants from JSPS KAKENHI.
Jens Kuhle: Jens Kuhle received speaker fees, research support, travel support, and/or served on advisory boards by ECTRIMS, Swiss MS Society, Swiss National Research Foundation, (320030_160221), University of Basel, Bayer, Biogen, Genzyme, Merck, Novartis, Protagen AG, Roche, Teva.
Jun-ichi Kira has received grants, consultant fees, speaking fees and/or honoraria from AMED, Health, Labour and Welfare Sciences Research Grants, MEXT KAKENHI, JSPS KAKENHI, Novartis Pharma, Mitsubishi Tanabe Pharma, Boehringer Ingelheim, Teijin Pharma, Takeda Pharmaceutical Company, Otsuka Pharmaceutical, Astellas Pharma, Pfizer Japan, Eisai.
Abstract: 213
Type: Scientific Session
Abstract Category: Pathology and pathogenesis of MS - Biomarkers
Introduction: Glial fibrillary acidic protein (GFAP) is an astrocytic protein with known increased CSF concentrations in neuromyelitis optica spectrum disorders (NMOSD). Neurofilament light chain (NfL) is an exclusively neuronal protein that has been shown to be a measure of disease activity and short- and longer term disability progression in multiple sclerosis (MS). It remains to be established whether serum GFAP (sGFAP) and NfL (sNfL) are associated with disease activity or worsening in NMOSD.
Objectives: To investigate whether sGFAP and sNfL levels are related to disease activity and disability in NMOSD and MS patients.
Methods: GFAP and NfL levels in CSF and sera were measured in healthy controls (HC, n = 49; 49 sera), NMOSD (n = 34; 43 CSF and 104 sera) and MS patients (n = 49; 53 CSF and 91 sera) by using a homebrew and commercially available ultrasensitive single-molecule array (Simoa) assay, respectively. The relation of sNfL and sGFAP levels to clinical parameters was assessed.
Results: We found a strong association between CSF and serum GFAP levels (NMOSD, r = 0.963, p < 0.0001; MS, r = 0.690, p < 0.0001) and between CSF and serum NfL levels (NMOSD, r = 0.746, p < 0.0001; MS, r = 0.842, p < 0.0001). sGFAP levels were correlated with age in HC, but not in NMOSD nor MS (p = 0.0087, 0.68, 0.91, respectively). sGFAP and sNfL levels were higher in NMOSD patients than in HC (p < 0.0001, both). Moreover, sGFAP levels in NMOSD were higher than those in MS patients (median: 199.4 versus 121.1 pg/ml, p < 0.0001). In NMOSD, sGFAP levels in acute relapse were higher than in remission (634.7 versus 141.6 pg/ml, p < 0.0001). sGFAP levels were associated with Expanded Disability Status Scale (EDSS) scores in MS patients.
Conclusions: Highly sensitive detection now allows reliable quantification of GFAP in blood samples from patients with NMOSD. These results suggest that besides sNfL, longitudinal GFAP level determinations in blood have the future potential to inform about disease activity and optimal treatment response in NMOSD.
Disclosure: Mitsuru Watanabe has received grant support from Japan Society for the Promotion of Science (JSPS KAKENHI Grant Number 17K16124) and GlaxoSmithKline.
Yuri Nakamura has received a grant and salary from Mitsubishi Tanabe Pharma, Bayer Yakuhin, Ltd., and Japan Blood Products Organization.
Zuzanna Michalak: nothing to disclose.
Fumie Hayashi: nothing to disclose.
Christian Barro has received travel support from Teva and Novartis.
Noriko Isobe has received grant support from JSPS KAKENHI 18K07529, Japan Intractable Disease Research Foundation, Mitsubishi Tanabe Pharma, Bayer Yakuhin, Ltd., and Japan Blood Products Organization.
Takuya Matsushita has received speaker honoraria payments from Mitsubishi Tanabe Pharma, Takeda Pharmaceutical Company and Biogen Japan.
Ryo Yamasaki has received grants from JSPS KAKENHI.
Jens Kuhle: Jens Kuhle received speaker fees, research support, travel support, and/or served on advisory boards by ECTRIMS, Swiss MS Society, Swiss National Research Foundation, (320030_160221), University of Basel, Bayer, Biogen, Genzyme, Merck, Novartis, Protagen AG, Roche, Teva.
Jun-ichi Kira has received grants, consultant fees, speaking fees and/or honoraria from AMED, Health, Labour and Welfare Sciences Research Grants, MEXT KAKENHI, JSPS KAKENHI, Novartis Pharma, Mitsubishi Tanabe Pharma, Boehringer Ingelheim, Teijin Pharma, Takeda Pharmaceutical Company, Otsuka Pharmaceutical, Astellas Pharma, Pfizer Japan, Eisai.