Journal of the Neurological Sciences
Volume 290, Issue 1 , Pages 16-21, 15 March 2010

Methylation patterns of cell-free plasma DNA in relapsing–remitting multiple sclerosis

  • Thomas Liggett

      Affiliations

    • Rush University Medical Center, Department of Neurological Sciences, Multiple Sclerosis Center, 1745 W. Harrison Street, Ste 309, Chicago, IL 60612, USA
    • These authors contributed equally to the experimental design and the microarray work.
    • ,
  • Anatoliy Melnikov

      Affiliations

    • Rush University Medical Center, Department of Radiation Oncology, 1750 W. Harrison Street, Jelke Bldg, 1303, Chicago, IL 60612, USA
    • These authors contributed equally to the experimental design and the microarray work.
    • ,
  • Shilpa Tilwalli

      Affiliations

    • Rush University Medical Center, Department of Neurological Sciences, Multiple Sclerosis Center, 1745 W. Harrison Street, Ste 309, Chicago, IL 60612, USA
    • ,
  • Qilong Yi

      Affiliations

    • ScienceDocs Inc., 10940 SW Barnes Road, Ste. 270, Portland, OR 97225, USA
    • ,
  • Haiyan Chen

      Affiliations

    • ScienceDocs Inc., 10940 SW Barnes Road, Ste. 270, Portland, OR 97225, USA
    • ,
  • Charles Replogle

      Affiliations

    • ScienceDocs Inc., 10940 SW Barnes Road, Ste. 270, Portland, OR 97225, USA
    • ,
  • Xuan Feng

      Affiliations

    • University of Chicago, Department of Neurology, 5841 S. Maryland Street, MC-2030, Chicago, IL 60637, USA
    • ,
  • Anthony Reder

      Affiliations

    • University of Chicago, Department of Neurology, 5841 S. Maryland Street, MC-2030, Chicago, IL 60637, USA
    • ,
  • Dusan Stefoski

      Affiliations

    • Rush University Medical Center, Department of Neurological Sciences, Multiple Sclerosis Center, 1745 W. Harrison Street, Ste 309, Chicago, IL 60612, USA
    • ,
  • Roumen Balabanov

      Affiliations

    • Rush University Medical Center, Department of Neurological Sciences, Multiple Sclerosis Center, 1745 W. Harrison Street, Ste 309, Chicago, IL 60612, USA
    • Corresponding Author InformationCorresponding authors. Levenson is to be contacted at Rush University Medical Center, Department of Radiation Oncology, 1750 W. Harrison Street, Jelke Bldg, 1303, Chicago, IL 60612, United States. Tel.: +1 312 942 0555. Balabanov, Rush University Medical Center, Department of Neurological Sciences, Multiple Sclerosis Center, 1745 W. Harrison Street, Chicago, IL 60612, United States. Tel.: +1 312 942 8011.
    • ,
  • Victor Levenson

      Affiliations

    • Rush University Medical Center, Department of Radiation Oncology, 1750 W. Harrison Street, Jelke Bldg, 1303, Chicago, IL 60612, USA
    • Corresponding Author InformationCorresponding authors. Levenson is to be contacted at Rush University Medical Center, Department of Radiation Oncology, 1750 W. Harrison Street, Jelke Bldg, 1303, Chicago, IL 60612, United States. Tel.: +1 312 942 0555. Balabanov, Rush University Medical Center, Department of Neurological Sciences, Multiple Sclerosis Center, 1745 W. Harrison Street, Chicago, IL 60612, United States. Tel.: +1 312 942 8011.

Received 13 October 2009; received in revised form 15 December 2009; accepted 17 December 2009. published online 11 January 2010.

Abstract 

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.

Conclusion

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.

Keywords: Multiple sclerosis, Cell-free plasma DNA, DNA methylation, Gene promoter, Biomarker, Microarray

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PII: S0022-510X(09)01021-1

doi:10.1016/j.jns.2009.12.018

Journal of the Neurological Sciences
Volume 290, Issue 1 , Pages 16-21, 15 March 2010

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