Methylation patterns of cell-free plasma DNA in relapsing-remitting multiple sclerosis.
BACKGROUND
There is growing interest for identification of new targets for biomarker development in multiple sclerosis (MS). The goal of this study was to compare the concentration and the methylation patterns of cell-free plasma DNA (cfpDNA) in patients with relapsing-remitting multiple sclerosis (RRMS) and healthy individuals.


METHODS
Three 30-patient cohorts were examined: patients with RRMS, in either remission or exacerbation, and healthy individuals as controls. Concentration of cfpDNA was determined using a standard fluorometric assay. Patterns of methylation in 56 gene promoters were determined by a microarray-based assay (MethDet-56). The data were analyzed to identify statistically relevant differences among the study groups.


RESULTS
The concentration of cfpDNA in patients with RRMS was four to eight-fold higher compared to healthy controls. Significant differences in cfpDNA methylation patterns were detected in all three comparisons: RRMS patients in remission versus healthy controls were recognized with 79.2% sensitivity and 92.9% specificity; RRMS patients in exacerbation versus healthy controls were recognized with 75.9% sensitivity and 91.5% specificity; and RRMS patients in exacerbation versus those in remission were recognized with 70.8% sensitivity and 71.2% specificity.


CONCLUSIONS
Based on our findings, we conclude that patients with RRMS display unique disease- and state-specific changes of cfpDNA. Our findings are of clinical significance as they could be used in the development of potentially new biomarkers for MS. This is the first report in our knowledge describing such changes of cfpDNA in patients with MS.
Liggett
Thomas
T
Rush University Medical Center, Department of Neurological Sciences, Multiple Sclerosis Center, Chicago, IL 60612, USA.
Melnikov
Anatoliy
A
Tilwalli
Shilpa
S
Yi
Qilong
Q
Chen
Haiyan
H
Replogle
Charles
C
Feng
Xuan
X
Reder
Anthony
A
Stefoski
Dusan
D
Balabanov
Roumen
R
Levenson
Victor
V
D000328:Adult; D015415:Biomarkers / Q000032:analysis / Q000097:blood; D015331:Cohort Studies; D004247:DNA / Q000032:analysis* / Q000097:blood*; D019175:DNA Methylation / Q000235:genetics*; D004252:DNA Mutational Analysis; D044127:Epigenesis, Genetic / Q000235:genetics; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D005820:Genetic Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000097:blood* / Q000175:diagnosis / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D010949:Plasma / Q000737:chemistry / Q000378:metabolism; D011237:Predictive Value of Tests; D011401:Promoter Regions, Genetic / Q000235:genetics; D012680:Sensitivity and Specificity; D015854:Up-Regulation / Q000235:genetics
D015415:Biomarkers; D005819:Genetic Markers; D004247:DNA