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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.
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It is part of: Neurology. Neuroimmunology & Neuroinflammation, 2021, vol. 8, num. 2
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ISSN: 2332-7812
Appears in Collections:Articles publicats en revistes (Biomedicina)

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