Serum GFAP and NfL levels in benign relapsing-remitting multiple sclerosis
Open accessAbstract
Objective We aimed to investigate serum glial fibrillary acidic protein (GFAP) and serum neurofilament light chain (NfL) levels as potential discriminative biomarkers between benign relapsing-remitting multiple sclerosis (BRRMS) and aggressive relapsing-remitting MS (ARRMS). Methods Serum GFAP and NfL levels were analyzed in patients with BRRMS (n = 34), ARRMS (n = 29), and healthy controls (n = 14) by using Single Molecule Array (Simoa). Patients with ARRMS had been treated with highly effective disease-modifying treatments (DMT) (fingolimod or natalizumab). Results Serum GFAP levels in both BRRMS (median 210.19 pg/ml, IQR 163.69-287.19) and in ARRMS (median 188.60 pg/ml, IQR39.23-244.93) were significantly higher (p = 0.035 and p = 0.034, respectively) compared to healthy controls (median 117.93 pg/ml, IQR 60.28-183.83). Serum GFAP levels did not differ between BRRMS and ARRMS. There were no statistical differences in NfL levels between BRRMS, ARRMS and healthy controls. GFAP level was significantly higher (p = 0.04) in BRRMS without DMT (median 216.04 pg/ml, IQR 188.60-274.79) than in those BRRMS patients who had used DMT (median 196.26 pg/ml, IQR 133.33-325.54). Conclusions We found elevated levels of serum GFAP in both BRRMS and ARRMS compared to healthy controls, reflecting astrocytic activation. Serum NfL did not differ between BRRMS and ARRMS, probably due to the stable inflammatory phase of the disease and effective DMT use in ARRMS. Single serum NfL and GFAP measurements cannot separate a patient with BRRMS from effectively treated ARRMS after a long history of the disease, thus consecutive samples are needed in the follow-up.
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Most studies of NfL rely on serum.
“Third, the inconsistent use of serum versus plasma further complicates comparisons, as most studies of NfL rely on serum.4,6,9,12–14”
From Establishing demographic-based normative values for neurofilament light chain and glial fibrillary acidic protein in serum and plasma samples (2026) · cites this paper as [4]
The Introduction says that NfL levels have mainly been reported in CSF-based studies in MS patients, although they can also be measured in serum. This paper measures serum NfL, but its statement about the broader MS literature runs contrary to the claim that most NfL studies rely on serum. (LLM, conf=0.87)
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Cites
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Borko, T. L., Ritchie, A., Selva, S., Sillau, S., Engebretson, E., Wolf, A. B., Alvarez, E., Gross, R., Gutierrez, E., Corboy, J., et al. (2026) · Multiple Sclerosis Journal – Experimental, Translational and Clinical · doi:10.1177/20552173261466440 · Cited by 1 · see citing works
- Authors
- Niiranen, M., Kontkanen, A., Jääskeläinen, O., Tertsunen, H.-M., Selander, T., Hartikainen, P., Huber, N., Solje, E., Haapasalo, A., Kokkola, T., Lohioja, T., Herukka, S.-K., Simula, S., & Remes, A. M.
- Affiliations
- Kuopio University Hospital (FI)
- University of Eastern Finland (FI)
- Mikkelin keskussairaala (FI)
- Oulu University Hospital (FI)
- Corresponding author
- Niiranen, Marja
- ORCID
- Venue
- Multiple Sclerosis and Related Disorders
- Publisher
- Elsevier BV
- Published
- 2021-11
- Volume
- 56
- Pages
- 103280
- ISSN
- 2211-0348 (ISSN-L)
- OpenAlex
- W3201903833
- Cited by
- 25
- References
- 2
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 7 · 2023: 6 · 2022: 6
- FWCI
- 3.17
- Type
- journal article
- Language
- en
- Open access
- green
- erepo.uef.fi
- Licence
- Locations
- Multiple Sclerosis and Related Disorders (publishedVersion)
- PubMed (publishedVersion)
- UEF eRepo (University of Eastern Finland) (submittedVersion, cc-by-nc-nd)
- Funders
- Academy of Finland (315459, 315460)
- Instrumentariumin Tiedesäätiö
- Kuopion Yliopistollinen Sairaala
- Päivikki ja Sakari Sohlbergin Säätiö
- Sigrid Juséliuksen Säätiö
- Orionin Tutkimussäätiö
- Itä-Suomen Yliopisto
- Finnish Brain Foundation
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Health Sciences › Medicine › Neurology › Peripheral Neuropathies and Disorders
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- glial fibrillary acidic protein, neurofilament light chain, serum biomarkers, disease-modifying therapy, fingolimod, natalizumab, astrocyte activation
- MeSH terms
- Fingolimod Hydrochloride, Natalizumab, Glial Fibrillary Acidic Protein, Humans, Intermediate Filaments, Biomarkers, Neurofilament Proteins, Multiple Sclerosis, Relapsing-Remitting
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