open access
Immune-cell BDNF expression in treatment-naïve relapsing-remitting multiple sclerosis patients and following one year of immunomodulation therapy
Affiliations- Division of Neurochemistry and Neuropathology, Department of Neurology, Poznan University of Medical Sciences (PUMS), 49 Przybyszewskiego Street, Poznan, Poland
- Department of Neurology and Cerebrovascular Disorders, Poznan University of Medical Sciences, L. Bierkowski Hospital, Poznań, Poland
- Chair & Department of Neurology, Poznan University of Medical Sciences, Poznan, Poland
open access
Abstract
Although neurons are the main source of neurotrophins in the healthy brain, neurotrophins can also be expressed in the immune system. We have previously shown that in relapsing-remitting multiple sclerosis (RRMS) lower immune-cell neurotrophin levels are associated with brain atrophy and cognitive impairment. The aim of the present study was to assess if immune-cell neurotrophin expression is impaired in MS as compared with the healthy controls, and to describe if these levels change in treatment-naïve RRMS patients, following one year of immunomodulation.
Fifty treatment-naïve RRMS patients were assessed at baseline and after one year of immunomodulation (beta-interferons/glatiramer acetate). The control group included 39 healthy subjects matched according to age and gender. Peripheral blood mononuclear cells (PBMCs) were isolated from heparinized blood using Ficoll-Histopaque gradient. The levels of brain-derived-neurotrophic-factor (BDNF), beta-nerve-growth-factor (beta-NGF), neurotrophin-3 (NT-3) and neurotrophin-4/5 (NT-4/5) were measured in PBMC lysates with ELISA.
BDNF levels were significantly lower in MS than in the healthy controls (median 613 vs. 1657pg/mg protein, p<0.001). After one year of immunomodulation, BDNF expression did not change significantly (p=0.06) on the group level. In 70% of patients there was no increase in BDNF level, and in 30% it increased. We observed no differences between treatment groups. Other neurotrophins were detected in a minority of MS samples (as opposed to the controls).
To conclude, we have shown that immune-cell production of neurotrophins is impaired in MS patients. In our MS cohort standard immunomodulation failed to restore normal BDNF levels in PBMCs within one year of therapy.
Abstract
Although neurons are the main source of neurotrophins in the healthy brain, neurotrophins can also be expressed in the immune system. We have previously shown that in relapsing-remitting multiple sclerosis (RRMS) lower immune-cell neurotrophin levels are associated with brain atrophy and cognitive impairment. The aim of the present study was to assess if immune-cell neurotrophin expression is impaired in MS as compared with the healthy controls, and to describe if these levels change in treatment-naïve RRMS patients, following one year of immunomodulation.
Fifty treatment-naïve RRMS patients were assessed at baseline and after one year of immunomodulation (beta-interferons/glatiramer acetate). The control group included 39 healthy subjects matched according to age and gender. Peripheral blood mononuclear cells (PBMCs) were isolated from heparinized blood using Ficoll-Histopaque gradient. The levels of brain-derived-neurotrophic-factor (BDNF), beta-nerve-growth-factor (beta-NGF), neurotrophin-3 (NT-3) and neurotrophin-4/5 (NT-4/5) were measured in PBMC lysates with ELISA.
BDNF levels were significantly lower in MS than in the healthy controls (median 613 vs. 1657pg/mg protein, p<0.001). After one year of immunomodulation, BDNF expression did not change significantly (p=0.06) on the group level. In 70% of patients there was no increase in BDNF level, and in 30% it increased. We observed no differences between treatment groups. Other neurotrophins were detected in a minority of MS samples (as opposed to the controls).
To conclude, we have shown that immune-cell production of neurotrophins is impaired in MS patients. In our MS cohort standard immunomodulation failed to restore normal BDNF levels in PBMCs within one year of therapy.
Keywords
Relapsing-remitting multiple sclerosis (RRMS), Neurotrophins, Neurotrophic factors, Brain-derived neurotrophic factor (BDNF), Immunomodulation
About this articleTitle
Immune-cell BDNF expression in treatment-naïve relapsing-remitting multiple sclerosis patients and following one year of immunomodulation therapy
Journal
Neurologia i Neurochirurgia Polska
Issue
Pages
483-489
Published online
2018-03-29
Page views
375
Article views/downloads
721
DOI
10.1016/j.pjnns.2018.03.006
Bibliographic record
Neurol Neurochir Pol 2018;52(4):483-489.
Keywords
Relapsing-remitting multiple sclerosis (RRMS)
Neurotrophins
Neurotrophic factors
Brain-derived neurotrophic factor (BDNF)
Immunomodulation
Authors
Alicja Kalinowska-Łyszczarz
Mikołaj A. Pawlak
Aleksandra Wyciszkiewicz
Krystyna Osztynowicz
Wojciech Kozubski
Sławomir Michalak
