Antivirus immune activity in multiple sclerosis correlates with MRI activity.
OBJECTIVE
The objective of this study was to determine whether reactivation of Epstein-Barr (EBV) or activation of the anti-EBV immune response correlates with MS disease activity on MR imaging.


METHODS
Subjects with early, active relapsing-remitting MS were studied for 16 weeks with blood and saliva samples collected every 2 weeks and brain MRI performed every 4 weeks. We isolated peripheral blood mononuclear cells from each blood sample and tested the immune response to EBV, autologous EBV-infected lymphoblastoid cell lines (LCL), human herpesvirus 6 (HHV6), varicella zoster virus (VZV), tetanus, and mitogens. We measured the proliferative response and the number of interferon-γ secreting cells with ELISPOT. We measured the amounts of EBV, HHV6, and VZV DNA in blood and saliva with quantitative PCR. On MRI, we measured number and volume of contrast enhancing and T2 lesions. We tested for correlation between the immunologic assays and the MRI results, assessing different time intervals between the MRI and immunologic assays.


RESULTS
We studied 20 subjects. Ten had enhancing lesions on one or more MRI scans and one had new T2 lesions without enhancement. The most significant correlation was between proliferation to autologous LCL and the number of combined unique active lesions on MRI 4 weeks later. Both proliferation and number of cells secreting interferon-γ in response to LCL correlated with the number of enhancing lesions 8 weeks later.


CONCLUSIONS
We find evidence for correlation of antiviral immune responses in the blood with subsequent disease activity on MRI scans.
Department of Neurology, University of Texas Health Science Center at Houston, Houston, TX, USA.
L B
LB
Latham
Clinical and Translational Sciences, University of Texas Health Science Center at Houston, Houston, TX, USA.
M J
MJ
Lee
Department of Neurology, University of Texas Health Science Center at Houston, Houston, TX, USA.
J A
JA
Lincoln
Department of Biology, University of Texas San Antonio, San Antonio, TX, USA.
N
N
Ji
Department of Biology, University of Texas San Antonio, San Antonio, TX, USA.
T G
TG
Forsthuber
Department of Neurology, University of Texas Health Science Center at Houston, Houston, TX, USA.
J W
JW
Lindsey
D000328:Adult; D020031:Epstein-Barr Virus Infections / Q000276:immunology; D005260:Female; D014645:Herpesvirus 3, Human / Q000276:immunology; D004854:Herpesvirus 4, Human / Q000276:immunology*; D015654:Herpesvirus 6, Human / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging / Q000639:trends*; D008297:Male; D009103:Multiple Sclerosis / Q000175:diagnosis* / Q000276:immunology* / Q000821:virology; D011446:Prospective Studies
Epstein-Barr virus; gadolinium enhancing lesions; human herpesvirus 6; magnetic resonance imaging; multiple sclerosis; varicella zoster virus