Konstance K. Knox, Lorri J. Lobeck,
Eric F. Maas, Donald R. Carrigan Milwaukee, WI
Supported By: Grant PP0751 from the National Multiple Sclerosis Society
Category: MS and Related Diseases
The goal of these studies was to assess multiple sclerosis (MS) patients for evidence of active human herpesvirus six (HHV-6) infections and to correlate those findings with the clinical and therapy status of the patients.
Several laboratories have presented data linking the pathogenesis of MS to active HHV-6 infections. Different diagnostic technologies have been used in these studies including immunohistochemical staining of tissues, polymerase chain reaction analysis of serum samples and isolation of the virus from blood samples. The majority of the work from our laboratory has involved staining of MS patient derived CNS and lymphoid tissues for HHV-6 antigens and isolation of the virus from peripheral blood leukocytes of MS patients by a rapid culture procedure (Knox et al.; Clin Infect Dis 2000; 31:894-903). In the studies described here we have used an alternate methodology, i.e. serum PCR, to address this issue.
Blood samples were obtained at the time of new clinical relapse in patients with relapsing-remitting MS and assessed for active HHV-6 infection by serum PCR. Then, several weeks later (mean interval:68 days), a second blood sample was obtained from the same patients and assessed for active HHV-6 infection. Patients'changes of Expanded Disability Status Scale (EDSS) from the relapse and treatments at the time samples were obtained were noted.
5 of 39 (13%) patients had at least one sample positive for active HHV-6 infection with viral loads varying from 9000 to 500,000 viral genomes per ml of serum. Variant typing of the positive samples was possible with 3 of the 5 positives, and 2 were HHV-6 variant A. Four of the five (80%) positive samples were obtained at the time of relapse whereas only one (20%) positive was observed in a patient after relapse. The HHV-6 positive patients suffered a larger change in their EDSS (mean EDSS change of 1.4) than the HHV-6 negative patients (mean EDSS change of 0.7). It was also found that the patients receiving either beta interferon or glatirimar acetate (copaxone) were less likely to be HHV-6 positive (2/30; 7%) than the patients receiving no treatment 3/9; 33%). Since the majority (>75%) of the patients on therapy were receiving beta interferon, the decreased positivity for active HHV-6 may reflect the known antiviral properties of beta interferon.
The findings presented here demonstrate that active HHV-6 infections can frequently be detected at the time of clinical relapse in patients with relapsing-remitting MS and confirm the work of other laboratories that have used serum PCR to detect such infections. Also, we observed that patients with active HHV-6 infections at the time of relapse show a greater degree of residual disability than HHV-6 negative patients and that patients who are receiving beta interferon or glatirimar acetate therapies are at reduced risk for the occurrence of detectable active HHV-6 infections.