Serum glial fibrillary acidic protein correlates with retinal structural damage in aquaporin-4 antibody positive neuromyelitis optica spectrum disorder

Ting-Yi Lin; Patrick Schindler; Ulrike Grittner; Frederike C Oertel; Angelo Lu; Seyedamirhosein Motamedi; Sunil Kumar Yadav; Ankelien S Duchow; Sven Jarius; Jens Kuhle; Pascal Benkert; Alexander U Brandt; Judith Bellmann-Strobl; Tanja Schmitz-Hübsch; Friedemann Paul; Klemens Ruprecht; Hanna G Zimmermann

doi:10.1016/j.msard.2022.104100

Serum glial fibrillary acidic protein correlates with retinal structural damage in aquaporin-4 antibody positive neuromyelitis optica spectrum disorder

Mult Scler Relat Disord. 2022 Nov:67:104100. doi: 10.1016/j.msard.2022.104100. Epub 2022 Aug 9.

Authors

Ting-Yi Lin¹, Patrick Schindler², Ulrike Grittner³, Frederike C Oertel⁴, Angelo Lu¹, Seyedamirhosein Motamedi¹, Sunil Kumar Yadav¹, Ankelien S Duchow⁵, Sven Jarius⁶, Jens Kuhle⁷, Pascal Benkert⁸, Alexander U Brandt⁹, Judith Bellmann-Strobl¹, Tanja Schmitz-Hübsch¹, Friedemann Paul², Klemens Ruprecht¹⁰, Hanna G Zimmermann¹¹

Affiliations

¹ Experimental and Clinical Research Center, A Cooperation Between the Max Delbrück Center for Molecular Medicine in the Helmholtz Association and the Charité - Universitätsmedizin Berlin, Berlin, Germany; Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; Max-Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany; NeuroCure Clinical Research Center, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
² Experimental and Clinical Research Center, A Cooperation Between the Max Delbrück Center for Molecular Medicine in the Helmholtz Association and the Charité - Universitätsmedizin Berlin, Berlin, Germany; Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; Max-Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany; NeuroCure Clinical Research Center, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; Department of Neurology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
³ Institute for Biometry and Clinical Epidemiology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Germany; Berlin Institute of Health, Berlin, Germany.
⁴ Experimental and Clinical Research Center, A Cooperation Between the Max Delbrück Center for Molecular Medicine in the Helmholtz Association and the Charité - Universitätsmedizin Berlin, Berlin, Germany; Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; Max-Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany; Department of Neurology, University of California San Francisco, CA, USA.
⁵ Experimental and Clinical Research Center, A Cooperation Between the Max Delbrück Center for Molecular Medicine in the Helmholtz Association and the Charité - Universitätsmedizin Berlin, Berlin, Germany; Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; Max-Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.
⁶ Molecular Neuroimmunology Group, Department of Neurology, University of Heidelberg, Heidelberg, Germany.
⁷ Neurology Clinic and Policlinic, MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel, Switzerland.
⁸ Clinical Trial Unit, Department of Clinical Research, University Hospital Basel, University of Basel, Basel, Switzerland.
⁹ Experimental and Clinical Research Center, A Cooperation Between the Max Delbrück Center for Molecular Medicine in the Helmholtz Association and the Charité - Universitätsmedizin Berlin, Berlin, Germany; Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; Max-Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany; Department of Neurology, University of California Irvine, CA, USA.
¹⁰ Department of Neurology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
¹¹ Experimental and Clinical Research Center, A Cooperation Between the Max Delbrück Center for Molecular Medicine in the Helmholtz Association and the Charité - Universitätsmedizin Berlin, Berlin, Germany; Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; Max-Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany; NeuroCure Clinical Research Center, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; Einstein Center Digital Future, Berlin, Germany. Electronic address: hanna.zimmermann@charite.de.

PMID: 36049341
DOI: 10.1016/j.msard.2022.104100

Abstract

Background: Aquaporin-4 immunoglobulin-G positive (AQP4-IgG⁺) neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune astrocytopathy associated with optic neuritis (ON). Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is an oligodendrocytopathy with a similar phenotype. Serum glial fibrillary acidic protein (sGFAP), an astrocyte-derived protein, is associated with disease severity in AQP4-IgG⁺ NMOSD. Serum neurofilament light (sNfL) indicates neuroaxonal damage. The objective was to investigate the association of sGFAP and sNfL with subclinical afferent visual system damage in clinically stable AQP4-IgG⁺ NMOSD and MOGAD patients.

Methods: In this cross-sectional study, clinically stable patients with AQP4-IgG⁺ NMOSD (N = 33) and MOGAD (N = 16), as diseased controls, underwent sGFAP and sNfL measurements by single molecule array, retinal optical coherence tomography and visually evoked potentials.

Results: Higher sGFAP concentrations were associated with thinner ganglion cell-inner plexiform layer (β (95% confidence interval (CI)) = -0.75 (-1.23 to -0.27), p = 0.007) and shallower fovea (average pit depth: β (95%CI) = -0.59 (-0.63 to -0.55), p = 0.020) in NMOSD non-ON eyes. Participants with pathological P100 latency had higher sGFAP (median [interquartile range]: 131.32 [81.10-179.34] vs. 89.50 [53.46-121.91] pg/ml, p = 0.024). In MOGAD, sGFAP was not associated with retinal structural or visual functional measures.

Conclusions: The association of sGFAP with structural and functional markers of afferent visual system damage in absence of ON suggests that sGFAP may be a sensitive biomarker for chronic disease severity in clinically stable AQP4-IgG⁺ NMOSD.

Keywords: Foveal morphometry; Myelin oligodendrocyte glycoprotein antibody-associated disease; Neuromyelitis optica spectrum disorder; Optical coherence tomography; Serum glial fibrillary acidic protein; Serum neurofilament light chain protein.

MeSH terms

Aquaporin 4
Autoantibodies
Biomarkers
Cross-Sectional Studies
Glial Fibrillary Acidic Protein / metabolism
Humans
Immunoglobulin G
Intermediate Filaments / metabolism
Neuromyelitis Optica*
Optic Neuritis* / diagnostic imaging
Retinal Diseases*

Substances

Glial Fibrillary Acidic Protein
Aquaporin 4
Autoantibodies
Immunoglobulin G
Biomarkers