Immune cell BDNF secretion is associated with white matter volume in multiple sclerosis.
OBJECTIVE
To investigate the relationship between immune cell secretion of brain-derived neurotrophic factor (BDNF) with clinical and MRI variables in multiple sclerosis (MS) patients.


BACKGROUND
BDNF exerts beneficial effects on neuronal growth and repair and is secreted by both neurons and immune cells. Consequently, it may mediate the crosstalk between the immune system and CNS in autoimmune diseases such as MS.


METHODS
Fifty-two relapsing MS patients (41 females, age: 48.8+/-6.6 years, disease duration: 12.7+/-8.4 years) were enrolled. Clinical and MRI measurements (including, T1-, T2- and contrast-enhancing (CE) lesion volumes (LVs); normalized measures of whole brain, white matter (WM) and gray matter (GM) volumes; diffusion weighted imaging measure of mean whole brain (WB) parenchyma diffusivity and magnetization transfer ratio (MTR) measures were obtained.


RESULTS
Immune cell BDNF secretion after anti-CD3 plus anti-CD28 stimulation was positively associated with increased CE-LV (p=0.026). The MTR of CE-LV and normal-appearing (NA) WM (NAWM) were negatively associated with immune cell BDNF secretion after anti-CD3 plus anti-CD28 stimulation. Immune cell BDNF secretion after anti-CD3 plus anti-CD28 was positively associated with higher WM volume (p=0.027). Immune cell BDNF secretion after anti-CD3 plus anti-CD28 stimulation was decreased with increasing disease duration (p=0.031). The BDNF secretion was independent of the BDNF Val66Met (dBSNP ID: rs6265) SNP genotype.


CONCLUSIONS
Immune cell BDNF secretion is associated with the sites of higher inflammatory activity as evidenced by CE lesions and may represent an important factor associated with the WM volume of patients with MS.
Weinstock-Guttman
Bianca
B
Jacobs Neurological Institute, Buffalo General Hospital, Buffalo, NY 14203, United States.
Zivadinov
Robert
R
Tamaño-Blanco
Miriam
M
Abdelrahman
Nadir
N
Badgett
Darlene
D
Durfee
Jackie
J
Hussein
Sara
S
Feichter
Joan
J
Patrick
Kara
K
Benedict
Ralph
R
Ramanathan
Murali
M
D000328:Adult; D000906:Antibodies / Q000494:pharmacology; D015703:Antigens, CD / Q000276:immunology; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D000068556:Interferon beta-1a; D016899:Interferon-beta / Q000494:pharmacology / Q000627:therapeutic use; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008715:Methionine / Q000235:genetics; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D014633:Valine / Q000235:genetics
D000906:Antibodies; D015703:Antigens, CD; D019208:Brain-Derived Neurotrophic Factor; D016899:Interferon-beta; D008715:Methionine; D014633:Valine; D000068556:Interferon beta-1a