CSF SERPINA3 Levels Are Elevated in Patients With Progressive MS
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CSF SERPINA3 Levels Are Elevated in Patients With Progressive MS. / Fissolo, Nicolás; Matute-Blanch, Clara; Osman, Mohamoud; Costa, Carme; Pinteac, Rucsanda; Miró, Berta; Sanchez, Alex; Brito, Verónica; Dujmovic, Irena; Voortman, Margarete; Khalil, Michael; Borràs, Eva; Sabidó, Eduard; Issazadeh-Navikas, Shohreh; Montalban, Xavier; Comabella Lopez, Manuel.
In: Neurology: Neuroimmunology & Neuroinflammation, Vol. 8, No. 2, 2021.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - CSF SERPINA3 Levels Are Elevated in Patients With Progressive MS
AU - Fissolo, Nicolás
AU - Matute-Blanch, Clara
AU - Osman, Mohamoud
AU - Costa, Carme
AU - Pinteac, Rucsanda
AU - Miró, Berta
AU - Sanchez, Alex
AU - Brito, Verónica
AU - Dujmovic, Irena
AU - Voortman, Margarete
AU - Khalil, Michael
AU - Borràs, Eva
AU - Sabidó, Eduard
AU - Issazadeh-Navikas, Shohreh
AU - Montalban, Xavier
AU - Comabella Lopez, Manuel
N1 - Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
U2 - 10.1212/NXI.0000000000000941
DO - 10.1212/NXI.0000000000000941
M3 - Journal article
C2 - 33436375
VL - 8
JO - Neurology: Neuroimmunology & Neuroinflammation
JF - Neurology: Neuroimmunology & Neuroinflammation
SN - 2332-7812
IS - 2
ER -
ID: 255357432