ABSTRACT
Introduction
Neuromyelitis optica spectrum disorder (NMOSD) is a relapsing, often debilitating neuroinflammatory disease, whose predominant clinical manifestations are longitudinally extensive transverse myelitis and optic neuritis. About 80% of the patients with an NMOSD phenotype have pathogenic autoantibodies against the astrocyte water channel aquaporin-4 (AQP4-IgG). While therapeutic options for NMOSD have greatly expanded in recent years, well-established biomarkers for prognosis or treatment response are still lacking. Glial fibrillary acidic protein (GFAP) is mainly expressed in astrocytes and can be detected in cerebrospinal fluid (CSF) and blood of patients with NMOSD.
Areas covered
Here, we comprehensively review the current knowledge on GFAP as a biomarker in NMOSD.
Expert opinion
In patients with AQP4-IgG+ NMOSD, GFAP levels are elevated in CSF and serum during acute attacks and correlate with disability, consistent with the pathophysiology of this antibody-mediated astrocytopathy. Serum GFAP levels tend to be higher in AQP4-IgG+ NMOSD than in its differential diagnoses, multiple sclerosis, and myelin oligodendrocyte antibody-associated disease. Importantly, serum GFAP levels in AQP4-IgG+ NMOSD during remission may be predictive of future disease activity. Serial serum GFAP measurements are emerging as a biomarker to monitor disease activity in AQP4-IgG+ NMOSD and could have the potential for application in clinical practice.
Article highlights
GFAP concentrations in CSF and blood are elevated in patients with NMOSD during attacks.
To a lesser degree, GFAP concentrations in the blood of patients with NMOSD are also elevated during remission, as compared to healthy individuals, patients with MS and MOGAD, but the overlap is substantial.
GFAP in CSF and blood correlates with disability in NMOSD.
GFAP in CSF and blood shows a marked, transient increase during NMOSD attacks.
GFAP in blood may be predictive of future attack risk in NMOSD.
Serial GFAP measurements in blood hold potential for disease monitoring in AQP4-IgG+ NMOSD.
Declaration of interest
O Aktas reports grants from the German Ministry of Education and Research (BMBF) and the German Research Foundation (DFG); grants and personal fees from Bayer HealthCare, Biogen, Genzyme, Novartis, Teva, and Viela Bio/Horizon Therapeutics; and personal fees from Alexion, Almirall, MedImmune, Merck Serono, and Roche. M Ringelstein received speaker honoraria from Novartis, Bayer Vital GmbH, Roche, Alexion, and Ipsen and travel reimbursements from Bayer Schering, Biogen Idec, Merz, Genzyme, Teva, Roche, and Merck, none related to this study. B Wildemann received grants from the German Ministry of Education and Research, Deutsche Forschungsgemeinschaft, Dietmar Hopp Foundation, Klaus Tschira Foundation, grants and personal fees from Merck, and personal fees from Alexion, Bayer, Biogen, Roche, none related to this work. F Paul served on the scientific advisory boards of Novartis and MedImmune; received travel funding and/or speaker honoraria from Bayer, Novartis, Biogen, Teva, Sanofi-Aventis/Genzyme, Merck Serono, Alexion, Chugai, MedImmune, and Shire; is an associate editor of Neurology: Neuroimmunology & Neuroinflammation; is an academic editor of PLoS ONE; consulted for Sanofi Genzyme, Biogen, MedImmune, Shire, and Alexion; received research support from Bayer, Novartis, Biogen, Teva, Sanofi-Aventis/Geynzme, Alexion, and Merck Serono; and received research support from the German Research Council, Werth Stiftung of the City of Cologne, German Ministry of Education and Research, Arthur Arnstein Stiftung Berlin, EU FP7 Framework Program, Arthur Arnstein Foundation Berlin, Guthy-Jackson Charitable Foundation, and NMSS. K Ruprecht received research support from Novartis, Merck Serono, the German Ministry of Education and Research, the European Union (821,283-2), Stiftung Charité (BIH Clinical Fellow Program), and the Arthur Arnstein Foundation; and received travel grants from the Guthy-Jackson Charitable Foundation. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
Reviewer disclosures
Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.