Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Multicenter Study
. 2025 Feb 1;82(2):168-175.
doi: 10.1001/jamaneurol.2024.4400.

Blood-Based Biomarkers for Identifying Disease Activity in AQP4-IgG-Positive Neuromyelitis Optica Spectrum Disorder

Su-Hyun Kim  1 , Ana Beatriz Ayroza Galvão Ribeiro Gomes  2   3   4   5   6 , Patrick Schindler  7   8   9 , Jae-Won Hyun  1 , Ki Hoon Kim  1 , Dong-Eun Lee  10 , Vinicius Andreoli Schoeps  5 , Aline de Moura Brasil Matos  5 , Natalia Trombini Mendes  5 , Samira Luisa Dos Apóstolos-Pereira  5 , Dagoberto Callegaro  5 , Jasmine Lerner  2   3   4   6 , Pascal Benkert  2   3   4   6 , Jens Kuhle  2   3   4   6 , Klemens Ruprecht  7 , Friedemann Paul  7   8   9 , Anne-Katrin Pröbstel  2   3   4   6 , Ho Jin Kim  1
Affiliations
Multicenter Study

Blood-Based Biomarkers for Identifying Disease Activity in AQP4-IgG-Positive Neuromyelitis Optica Spectrum Disorder

Su-Hyun Kim et al. JAMA Neurol. .

Abstract

Importance: The temporal dynamics of serum glial fibrillary acidic protein (sGFAP) and serum neurofilament light chain (sNfL) as biomarkers of disease activity for neuromyelitis optica spectrum disorder (NMOSD) remain underexplored.

Objective: To determine optimal timing for assessing sGFAP and sNfL, establish cutoff values differentiating between attacks and remissions in NMOSD, and evaluate these findings across independent cohorts.

Design, setting, and participants: This retrospective, longitudinal, multicenter cohort study was conducted among patients with aquaporin-4 antibody (AQP4-IgG)-positive NMOSD. Patients with available stored serum samples were included, totaling 181 patients with 625 samples. Discovery cohort samples were collected from February 2008 to October 2023 and validation cohort samples were collected from January 2013 to October 2023. A combined analysis of both cohorts was conducted from November 2023 to March 2024.

Exposures: sNfL and sGFAP concentrations, measured by a single-molecule array assay.

Main outcomes and measures: The primary outcomes were the optimal timing of assessing sGFAP and sNfL and the adjusted cutoff values for evaluating disease activity in NMOSD.

Results: The discovery cohort consisted of 366 samples from 78 Korean patients (median [IQR] age, 35 [30-42] years; 73 female patients [95%]), while the validation cohort included 190 samples from 34 German patients (median [IQR] age, 54 [39-61] years; 32 female patients [94%]) and 69 samples from 69 Brazilian patients (median [IQR] age, 46 [35-55] years; 62 female patients [90%]). Six-month postattack temporal biomarker dynamics were analyzed in 202 samples from 74 patients in the discovery cohort: sGFAP levels peaked within the first week and sNfL levels peaked at 5 weeks postattack. The optimal time frames for evaluating attacks were within 1 week for sGFAP and from 1 to 8 weeks for sNfL, with remission defined as at least 6 months postattack. z Score cutoffs of 3.0 for sGFAP and 2.1 for sNfL effectively distinguished between attack and remission phases, indicated by area under the curve values of 0.95 (95% CI, 0.88-1.02) and 0.87 (95% CI, 0.82-0.91), respectively. The discovery cohort time frames and cutoff values were applied to the validation cohort, achieving 71% sensitivity and 94% specificity for sNfL and 100% sensitivity and specificity for sGFAP in the German and Brazilian cohorts.

Conclusions and relevance: This longitudinal cohort study established optimal timing and thresholds for sGFAP and sNfL, which were consistent in independent cohorts, supporting these biomarkers' effectiveness in distinguishing NMOSD attacks from remission.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Disclosures: Dr S. Kim reported grants from the National Cancer Center (2210330) during the conduct of the study and lecture or consulting fees or honoraria from Bayer Schering Pharma, Biogen, Genzyme, Merck Serono, and UCB. Dr Gomes reported a research grant to her institution for the collection and shipment of samples from Roche and grants from ECTRIMS (ECTRIMS Clinical Fellowship) and the Swiss government (Swiss Government Excellence Scholarship) during the conduct of the study. Dr Schindler reported personal fees from Alexion, Roche, and UCB; speaker’s honoraria from Roche and UCB; travel support from Alexion and UCB; and serving on an advisory board for Alexion outside the submitted work. Dr Matos reported honoraria from the speakers’ bureaus of Novartis and Biogen outside the submitted work. Dr Kuhle reported grants from Biogen, Bristol Myers Squibb, Merck, Novartis, the Progressive MS Alliance, Quanterix, Roche, Stata DX, the Swiss MS Society, and the Swiss National Research Foundation and personal fees from Alnylam, Immunic, Merck, and Neurogenesis outside the submitted work. Dr Ruprecht reported grants from the Guthy-Jackson Charitable Foundation during the conduct of the study; grants from the Arthur Arnstein Foundation, the European Union (8212832-2), the German Ministry of Education and Research, Merck Serono, Novartis, and Stiftung Charité outside the submitted work; and personal fees from Novartis and Virion Serion outside the submitted work. Dr Pröbstel reported grants from the Fondation Pierre Mercier pour la Science, the Goldschmidt Jacobson Foundation, the Gottfried & Julia Bangerter-Rhyner-Stiftung, the Propatient Research Foundation, and the Swiss National Science Foundation (211318 and 194609) during the conduct of the study; personal fees from Biogen, Novartis, Roche, and UCB outside the submitted work; and a patent pending. Dr H. Kim reported grants from AprilBio, Eisai, the National Research Foundation of Korea, and UCB; personal fees from Alexion, Altos Biologics, AstraZeneca, Biogen, Daewoong Pharmaceutical, Eisai, GC Pharma, Handok Pharmaceutical, Kaigene, Kolon Life Science, MDimune, Merck, Mitsubishi Tanabe Pharma, Roche, and Sanofi; and serving as coeditor for Multiple Sclerosis Journal outside the submitted work. No other disclosures were reported.

Similar articles

See all similar articles

Cited by

References

    1. Hyun JW, Kim Y, Kim SY, Lee MY, Kim SH, Kim HJ. Investigating the presence of interattack astrocyte damage in neuromyelitis optica spectrum disorder: longitudinal analysis of serum glial fibrillary acidic protein. Neurol Neuroimmunol Neuroinflamm. 2021;8(3):3965. doi:10.1212/NXI.0000000000000965 - DOI - PMC - PubMed
    1. Kim H, Lee EJ, Kim S, et al. . Longitudinal follow-up of serum biomarkers in patients with neuromyelitis optica spectrum disorder. Multiple Scler. 2022;28(4):512-521. doi:10.1177/13524585211024978 - DOI - PubMed
    1. Watanabe M, Nakamura Y, Michalak Z, et al. . Serum GFAP and neurofilament light as biomarkers of disease activity and disability in NMOSD. Neurology. 2019;93(13):e1299-e1311. doi:10.1212/WNL.0000000000008160 - DOI - PubMed
    1. Chang X, Huang W, Wang L, et al. . Serum neurofilament light and GFAP are associated with disease severity in inflammatory disorders with aquaporin-4 or myelin oligodendrocyte glycoprotein antibodies. Front Immunol. 2021;12:647618. doi:10.3389/fimmu.2021.647618 - DOI - PMC - PubMed
    1. Aktas O, Hartung HP, Smith MA, et al. ; N-MOmentum study investigators . Serum neurofilament light chain levels at attack predict post-attack disability worsening and are mitigated by inebilizumab: analysis of four potential biomarkers in neuromyelitis optica spectrum disorder. J Neurol Neurosurg Psychiatry. 2023;94(9):757-768. doi:10.1136/jnnp-2022-330412 - DOI - PMC - PubMed

Publication types

LinkOut - more resources