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Title: | CSF SERPINA3 Levels Are Elevated in Patients With Progressive MS |
Author: | Fissolo, Nicolás Matute Blanch, Clara Osman, Mohamoud Costa, Carme Pinteac, Rucsanda Miró, Berta Sànchez, Àlex (Sànchez Pla) Brito, Verónica Dujmovic, Irena Voortman, Margarete Khalil, Michael Borràs, Eva Sabidó Aguadé, Eduard Issazadeh Navikas, Shohreh Montalbán Gairín, Xavier Comabella, Manuel |
Keywords: | Esclerosi múltiple Marcadors bioquímics Models animals en la investigació Líquid cefalorraquidi Inhibidors enzimàtics Multiple sclerosis Biochemical markers Animal models in research Cerebrospinal fluid Enzyme inhibitors |
Issue Date: | 12-Jan-2021 |
Publisher: | American Academy of Neurology |
Abstract: | Objective: To identify biomarkers associated with progressive phases of MS and with neuroprotective potential. Methods: Combined analysis of the transcriptional and proteomic profiles obtained in CNS tissue during chronic progressive phases of experimental autoimmune encephalomyelitis (EAE) with the transcriptional profile obtained during the differentiation of murine neural stem cells into neurons. Candidate biomarkers were measured by ELISA in the CSF of 65 patients with MS (29 with relapsing-remitting MS [RRMS], 20 with secondary progressive MS, and 16 with primary progressive MS [PPMS]) and 30 noninflammatory neurologic controls (NINCs). Results: Integrative analysis of gene and protein expression data identified 2 biomarkers, the serine protease inhibitor Serpina3n and the calcium-binding protein S100A4, which were upregulated in chronic progressive EAE and whose expression was induced during neuronal differentiation. Immunofluorescence studies revealed a primarily neuronal expression of S100A4 and Serpina3n during EAE. CSF levels of SERPINA3, the human ortholog of murine Serpina3n, and S100A4 were increased in patients with MS compared with NINCs (SERPINA3: 1,320 vs 838.6 ng/mL, p = 0.0001; S100A4: 1.6 vs 0.8 ng/mL, p = 0.02). Within the MS group, CSF SERPINA3 levels were significantly elevated in patients with progressive forms, mainly patients with PPMS compared with patients with RRMS (1,617 vs 1,129 ng/mL, p = 0.02) and NINCs (1,617 vs 838.6 ng/mL, p = 0.0001). Of interest, CSF SERPINA3 levels significantly correlated with CSF neurofilament light chain levels only in the PPMS group (r = 0.62, p = 0.01). Conclusion: These results point to a role of SERPINA3 as a biomarker associated with the progressive forms of MS, particularly PPMS. |
Note: | Reproducció del document publicat a: https://doi.org/10.1212/NXI.0000000000000941 |
It is part of: | Neurology. Neuroimmunology & Neuroinflammation, 2021, vol. 8, num. 2 |
URI: | http://hdl.handle.net/2445/184676 |
Related resource: | https://doi.org/10.1212/NXI.0000000000000941 |
ISSN: | 2332-7812 |
Appears in Collections: | Articles publicats en revistes (Biomedicina) |
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