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Neurofilament light and glial fibrillary acidic protein in multiple sclerosis
Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurologi.
Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurologi.
Vise andre og tillknytning
2004 (engelsk)Inngår i: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 63, nr 9, s. 1586-1590Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Objective: To evaluate levels of neurofilament light (NFL) and glial fibrillary acidic protein (GFAP) in CSF from patients with multiple sclerosis (MS) in relation to clinical progress of the disease.

Methods: CSF levels of NFL and GFAP were determined by sensitive ELISAs in 99 patients with different subtypes of MS, classified in terms of “ongoing relapse” or “clinically stable disease,” and 25 control subjects. Levels were compared with paraclinical data such as immunoglobulin G index and inflammatory cell count in the CSF, and the levels were related to Expanded Disability Status Scale score and progression index at clinical follow-up evaluations later in the disease course.

Results: NFL and GFAP levels were elevated in MS patients as compared with control subjects (p < 0.001). The NFL levels were higher at relapses, whereas GFAP levels were unaffected. High NFL levels correlated with progression in patients with an active relapse (r = 0.49; p < 0.01) and in clinically stable patients (r = 0.29; p < 0.05). GFAP correlated to progression in the total patient cohort (r = 0.24; p < 0.05). Moreover, a strong correlation between NFL levels and inflammatory cell counts was evident in the group of patients with an ongoing relapse (r = 0.52; p = 0.001).

Conclusions: CSF levels of neurofilament light and glial fibrillary acidic protein may have prognostic value in multiple sclerosis.

sted, utgiver, år, opplag, sider
2004. Vol. 63, nr 9, s. 1586-1590
HSV kategori
Identifikatorer
URN: urn:nbn:se:umu:diva-4219PubMedID: 15534240OAI: oai:DiVA.org:umu-4219DiVA, id: diva2:143222
Tilgjengelig fra: 2004-11-09 Laget: 2004-11-09 Sist oppdatert: 2018-06-09bibliografisk kontrollert
Inngår i avhandling
1. Neurofilament light as a marker for neurodegenerative diseases
Åpne denne publikasjonen i ny fane eller vindu >>Neurofilament light as a marker for neurodegenerative diseases
2004 (engelsk)Doktoravhandling, med artikler (Annet vitenskapelig)
Abstract [en]

Neurofilaments are the main cytoskeletal constituents in neuronal cells. They are belived to be important for maintaining the structural integrity and calibre of axons and dendrites thereby influencing the conduction velocity of nerve impulses.The neurofilament chains are divided into three groups according to their molecular size, neurofilament light (NF-L), neurofilament medium (NF-M) and neurofilament heavy (NF-H). The neurofilaments are obligate heteropolymers in vivo in which NF-L forms the backbone to which the heavier chains copolymerize to form the 10 nm neurofilament fibre.

Different degenerative processes in the brain raise significant interest owing to the increasing mean age in the western world. Such diseases include amyotrophic lateral sclerosis, vascular dementia, frontal lobe dementia, progressive supra-nuclear paralysis, multiple system atrophy, low pressure hydrocephalus, and multiple sclerosis (MS).

We have been able to generate six highly specific monoclonal antibodies for NF-L, and four independent epitopes were elucidated using Biacore and V8 protease degradation. Antibody 2:1 and 47:3 were selected components in a two-site ELISA assay for detection of NF-L in body fluids owing to their outstanding abililty to bind the antigen. The assay has a least detectable dose of 60 ng/l and a standard range of 60 to 64 000 ng/l. The assay was validated on its ability to detect changes of NF-L levels in CSF in patients with different neurological diseases. These were cerebral infarction, amyotrophic lateral sclerosis, relapsing remitting MS, extrapyramidal symptoms, and late onset Alzheimer’s disease. All the patient groups displayed significantly elevated NF-L levels as compared to the controls. We also tested the assay’s ability to monitor the amount of axonal breakdown in an animal model of MS. The NF-L levels were found to be elevated in rodents with chronic experimental autoimmune encephalomyelitis, giving a possible tool for monitoring new treatment strategies for axonal protection in MS. When studying a large population based MS material, we found axonal breakdown to be present early in the disease course and the breakdown was observed both in active relapse and clinically stable disease, indicative of ongoing neurodegeneration. NF-L levels were correlated to progression index, that is, high NF-L levels detected early in disease predict a fast progression of the disease. The amount of glial fibrillary acidic protein, a cytoskeletal protein found in astrocytes, was also quantified and was shown to be a good marker for the more progressive MS subtypes, that is, primary progressive and secondary progressive disease, indicating formation of astrocytic scars and activation of astrocytes.

The test dealt with in this thesis has the potential to identify the slow chronic degenerative diseases with progressive disappearance of nerve cells and their large myelinated axons. There is a significant need clinically to be able to quantify such types of cell degeneration in relation to the progressive disappearance of nerve functions and to relate these different conditions to treatment regimens, disease progress, and prognosis.

sted, utgiver, år, opplag, sider
Umeå: Klinisk mikrobiologi, 2004. s. 69
Serie
Umeå University medical dissertations, ISSN 0346-6612 ; 930
Emneord
Immunology, Neurofilament protein, ELISA, Cerebrospinal fluid, Neurodegenerative diseases, Immunologi
HSV kategori
Forskningsprogram
immunologi
Identifikatorer
urn:nbn:se:umu:diva-357 (URN)91-7305-769-X (ISBN)
Disputas
2004-12-03, E04, 6E, Norrlands Universitetssjukhus, Umeå, 09:00
Opponent
Veileder
Tilgjengelig fra: 2004-11-09 Laget: 2004-11-09 Sist oppdatert: 2018-06-09bibliografisk kontrollert

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