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BACKGROUND: Multiple sclerosis (MS) is a neurodegenerative autoimmune disease. Clinical examination and magnetic resonances (MRI) are used for diagnosis and monitoring, but biological biomarkers would be fundamental. Neurofilament light-chain (NF-L) are cytoskeletal proteins released upon axonal damage in the cerebrospinal fluid (CSF) and, in low concentration, in serum (sNF-L). Now, it is possible to measure sNF-L with the sensitive Simoa technology. Whilst correlation between CSF and clinical outcomes as well as sNF-L is established, the application of sNF-L dosing in clinical practice is still to be addressed. METHODS: We measured sNF-L in 79 healthy participants and 1021 patients by single molecules array assay. RESULTS: 1) we established clinically applicable cut-off values for each age decade testing healthy individuals, later used to interpret sNF-L levels in individual patients. 2) progressive MS patients showed higher sNF-L levels and greater prevalence of high sNFL levels relative to Relapse-Remitting patients. 3) clinically active patients showed higher sNF-L levels and greater prevalence of high sNFL levels relative to stable patients. 4) disease-modifying therapies notably lower sNF-L in patients treated for more than 12 months. CONCLUSION: sNF-L correlate with MRI and clinical outcomes in MS, showing its potential as monitoring and treatment decision biomarker. The use of clinically applicable cut-off values could introduce sNF-L dosing in the everyday practice on individual patients.

BACKGROUND: Multiple sclerosis (MS) is a neurodegenerative autoimmune disease. Clinical examination and magnetic resonances (MRI) are used for diagnosis and monitoring, but biological biomarkers would be fundamental. Neurofilament light-chain (NF-L) are cytoskeletal proteins released upon axonal damage in the cerebrospinal fluid (CSF) and, in low concentration, in serum (sNF-L). Now, it is possible to measure sNF-L with the sensitive Simoa technology. Whilst correlation between CSF and clinical outcomes as well as sNF-L is established, the application of sNF-L dosing in clinical practice is still to be addressed. BACKGROUND: Multiple sclerosis (MS) is a neurodegenerative autoimmune disease. Clinical examination and magnetic resonances (MRI) are used for diagnosis and monitoring, but biological biomarkers would be fundamental. Neurofilament light-chain (NF-L) are cytoskeletal proteins released upon axonal damage in the cerebrospinal fluid (CSF) and, in low concentration, in serum (sNF-L). Now, it is possible to measure sNF-L with the sensitive Simoa technology. Whilst correlation between CSF and clinical outcomes as well as sNF-L is established, the application of sNF-L dosing in clinical practice is still to be addressed. METHODS: We measured sNF-L in 79 healthy participants and 1021 patients by single molecules array assay. RESULTS: 1) we established clinically applicable cut-off values for each age decade testing healthy individuals, later used to interpret sNF-L levels in individual patients. 2) progressive MS patients showed higher sNF-L levels and greater prevalence of high sNFL levels relative to Relapse-Remitting patients. 3) clinically active patients showed higher sNF-L levels and greater prevalence of high sNFL levels relative to stable patients. 4) disease-modifying therapies notably lower sNF-L in patients treated for more than 12 months. CONCLUSION: sNF-L correlate with MRI and clinical outcomes in MS, showing its potential as monitoring and treatment decision biomarker. The use of clinically applicable cut-off values could introduce sNF-L dosing in the everyday practice on individual patients.

Applicability of serum neurofilament light-chain detection in multiple sclerosis clinical practice

BAVA, CECILIA IRENE
2019/2020

Abstract

BACKGROUND: Multiple sclerosis (MS) is a neurodegenerative autoimmune disease. Clinical examination and magnetic resonances (MRI) are used for diagnosis and monitoring, but biological biomarkers would be fundamental. Neurofilament light-chain (NF-L) are cytoskeletal proteins released upon axonal damage in the cerebrospinal fluid (CSF) and, in low concentration, in serum (sNF-L). Now, it is possible to measure sNF-L with the sensitive Simoa technology. Whilst correlation between CSF and clinical outcomes as well as sNF-L is established, the application of sNF-L dosing in clinical practice is still to be addressed. BACKGROUND: Multiple sclerosis (MS) is a neurodegenerative autoimmune disease. Clinical examination and magnetic resonances (MRI) are used for diagnosis and monitoring, but biological biomarkers would be fundamental. Neurofilament light-chain (NF-L) are cytoskeletal proteins released upon axonal damage in the cerebrospinal fluid (CSF) and, in low concentration, in serum (sNF-L). Now, it is possible to measure sNF-L with the sensitive Simoa technology. Whilst correlation between CSF and clinical outcomes as well as sNF-L is established, the application of sNF-L dosing in clinical practice is still to be addressed. METHODS: We measured sNF-L in 79 healthy participants and 1021 patients by single molecules array assay. RESULTS: 1) we established clinically applicable cut-off values for each age decade testing healthy individuals, later used to interpret sNF-L levels in individual patients. 2) progressive MS patients showed higher sNF-L levels and greater prevalence of high sNFL levels relative to Relapse-Remitting patients. 3) clinically active patients showed higher sNF-L levels and greater prevalence of high sNFL levels relative to stable patients. 4) disease-modifying therapies notably lower sNF-L in patients treated for more than 12 months. CONCLUSION: sNF-L correlate with MRI and clinical outcomes in MS, showing its potential as monitoring and treatment decision biomarker. The use of clinically applicable cut-off values could introduce sNF-L dosing in the everyday practice on individual patients.
Applicability of serum neurofilament light-chain detection in multiple sclerosis clinical practice
BACKGROUND: Multiple sclerosis (MS) is a neurodegenerative autoimmune disease. Clinical examination and magnetic resonances (MRI) are used for diagnosis and monitoring, but biological biomarkers would be fundamental. Neurofilament light-chain (NF-L) are cytoskeletal proteins released upon axonal damage in the cerebrospinal fluid (CSF) and, in low concentration, in serum (sNF-L). Now, it is possible to measure sNF-L with the sensitive Simoa technology. Whilst correlation between CSF and clinical outcomes as well as sNF-L is established, the application of sNF-L dosing in clinical practice is still to be addressed. METHODS: We measured sNF-L in 79 healthy participants and 1021 patients by single molecules array assay. RESULTS: 1) we established clinically applicable cut-off values for each age decade testing healthy individuals, later used to interpret sNF-L levels in individual patients. 2) progressive MS patients showed higher sNF-L levels and greater prevalence of high sNFL levels relative to Relapse-Remitting patients. 3) clinically active patients showed higher sNF-L levels and greater prevalence of high sNFL levels relative to stable patients. 4) disease-modifying therapies notably lower sNF-L in patients treated for more than 12 months. CONCLUSION: sNF-L correlate with MRI and clinical outcomes in MS, showing its potential as monitoring and treatment decision biomarker. The use of clinically applicable cut-off values could introduce sNF-L dosing in the everyday practice on individual patients.
TEMPIA, FILIPPO
IMPORT TESI SOLO SU ESSE3 DAL 2018
Corso di Laurea Magistrale
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Descrizione: APPLICABILITY OF SERUM NEUROFILAMENT LIGHT-CHAIN DETECTION IN MULTIPLE SCLEROSIS CLINICAL PRACTICE
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.14240/3627