A Minimally-invasive Blood-derived Biomarker of Oligodendrocyte Cell-loss in Multiple Sclerosis

被引:28
作者
Olsen, John A. [1 ]
Kenna, Lauren A. [1 ]
Tipon, Regine C. [1 ]
Spelios, Michael G. [1 ]
Stecker, Mark M. [2 ]
Akirav, Eitan M. [1 ,3 ]
机构
[1] Winthrop Univ Hosp, Islet Biol, Res Inst, Mineola, NY 11501 USA
[2] Winthrop Univ Hosp, Dept Neurosci, Mineola, NY 11501 USA
[3] SUNY Stony Brook, Stony Brook, NY 11794 USA
关键词
Relapsing-remitting multiple sclerosis; Oligodendrocyte; Cuprizone; Human patients; Circulating free DNA; Biomarker discovery; CENTRAL-NERVOUS-SYSTEM; MICROSATELLITE ALTERATIONS; GLYCOPROTEIN MOG; CIRCULATING DNA; CANCER PATIENTS; MYELIN; REMYELINATION; EXPRESSION; CONDUCTION; DEATH;
D O I
10.1016/j.ebiom.2016.06.031
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Multiple sclerosis (MS) is a neurodegenerative disease of the central nervous system (CNS). Minimally invasive biomarkers of MS are required for disease diagnosis and treatment. Differentially methylated circulating-free DNA (cfDNA) is a useful biomarker for disease diagnosis and prognosis, and may offer to be a viable approach for understanding MS. Here, methylation-specific primers and quantitative real-time PCR were used to study methylation patterns of the myelin oligodendrocyte glycoprotein (MOG) gene, which is expressed primarily in myelin-producing oligodendrocytes (ODCs). MOG-DNA was demethylated in O4(+) ODCs in mice and in DNA from human oligodendrocyte precursor cells (OPCs) when compared with other cell types. In the cuprizonefed mouse model of demyelination, ODC derived demethylated MOG cfDNA was increased in serum and was associated with tissue-wide demyelination, demonstrating the utility of demethylated MOG cfDNA as a biomarker of ODC death. Collected sera from patients with active (symptomatic) relapsing-remitting MS (RRMS) demonstrated a higher signature of demethylated MOG cfDNA when compared with patients with inactive disease and healthy controls. Taken together, these results offer a minimally invasive approach to measuring ODC death in the blood of MS patients that may be used to monitor disease progression. (C) 2016 The Authors. Published by Elsevier B.V.
引用
收藏
页码:227 / 235
页数:9
相关论文
共 29 条
[1]  
Adelman Gabriel, 2013, J Med Econ, V16, P639, DOI 10.3111/13696998.2013.778268
[2]   Detection of β cell death in diabetes using differentially methylated circulating DNA [J].
Akirav, Eitan M. ;
Lebastchi, Jasmin ;
Galvan, Eva M. ;
Henegariu, Octavian ;
Akirav, Michael ;
Ablamunits, Vitaly ;
Lizardi, Paul M. ;
Herold, Kevan C. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2011, 108 (47) :19018-19023
[3]   ELECTRON MICROSCOPIC DEMONSTRATION OF CONNECTIONS BETWEEN GLIA AND MYELIN SHEATHS IN DEVELOPING MAMMALIAN CENTRAL NERVOUS SYSTEM [J].
BUNGE, MB ;
PAPPAS, GD ;
BUNGE, RP .
JOURNAL OF CELL BIOLOGY, 1962, 12 (02) :448-&
[4]   GLIAL CELLS AND CENTRAL MYELIN SHEATH [J].
BUNGE, RP .
PHYSIOLOGICAL REVIEWS, 1968, 48 (01) :197-+
[5]  
Chen XQ, 1996, NAT MED, V2, P1033
[6]   The regional distribution of myelin oligodendrocyte glycoprotein (MOG) in the developing rat CNS: An in vivo immunohistochemical study [J].
Coffey, JC ;
McDermott, KW .
JOURNAL OF NEUROCYTOLOGY, 1997, 26 (03) :149-161
[7]   Liquid biopsy: monitoring cancer-genetics in the blood [J].
Crowley, Emily ;
Di Nicolantonio, Federica ;
Loupakis, Fotios ;
Bardelli, Alberto .
NATURE REVIEWS CLINICAL ONCOLOGY, 2013, 10 (08) :472-484
[8]  
Felts PA, 1997, J NEUROSCI, V17, P7267
[9]   Axonal damage in acute multiple sclerosis lesions [J].
Ferguson, B ;
Matyszak, MK ;
Esiri, MM ;
Perry, VH .
BRAIN, 1997, 120 :393-399
[10]   Molecular biomarkers in cerebrospinal fluid of multiple sclerosis patients [J].
Fitzner, Brit ;
Hecker, Michael ;
Zettl, Uwe Klaus .
AUTOIMMUNITY REVIEWS, 2015, 14 (10) :903-913