CSF SERPINA3 Levels Are Elevated in Patients With Progressive MS
Fissolo, Nicolás (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Matute-Blanch, Clara (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Osman, Mohamoud (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Costa, Carme (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Pinteac, Rucsanda (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Miró, Berta (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Sánchez, Alex (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Brito, Verónica (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Dujmovic, Irena (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Voortman, Margarete (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Khalil, Michael (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Borràs, Eva (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Sabidó, Eduard (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Issazadeh-Navikas, Shohreh (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Montalban, Xavier (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Comabella, Manuel (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Universitat Autònoma de Barcelona

Date:	2021
Abstract:	To identify biomarkers associated with progressive phases of MS and with neuroprotective potential. 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). 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). These results point to a role of SERPINA3 as a biomarker associated with the progressive forms of MS, particularly PPMS.
Grants:	Instituto de Salud Carlos III PI17/00596 Agència de Gestió d'Ajuts Universitaris i de Recerca 2017 SGR 0527 Ministerio de Economía y Competitividad RD16/0015/0004
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Published in:	Neurology® neuroimmunology & neuroinflammation, Vol. 8 (january 2021) , ISSN 2332-7812

DOI: 10.1212/NXI.0000000000000941
PMID: 33436375

15 p, 1.2 MB

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