Increased spontaneous ex vivo apoptosis and subset alterations in peripheral blood T cells from patients with multiple sclerosis.

In order to characterize the immunophenotype and the lymphocyte apoptosis in multiple sclerosis (MS) patients, the peripheral blood lymphocytes of 46 MS patients and 12 healthy volunteers were studied by flow cytometry. Immunophenotypic alterations included significant increases in T CD4+ lymphocytes and reductions in the percentages of CD3+ and CD8+ T cells. After 24 h of culture spontaneous apoptosis was increased in almost T lymphocyte subsets from MS patients and it was significantly higher in those patients who had suffered more than two relapses in the two previous years. The incidence of spontaneous apoptosis was not dependent on FasL-Fas interactions and correlated with the percentages of cells positive for active caspases but not with percentages of Fas+ cells. The increased susceptibility to apoptosis of peripheral blood T lymphocytes from MS patients is difficult to reconcile with the previously proposed role of a defective lymphocyte apoptosis in the pathophysiology of MS.

Active human herpesvirus 6 infection in patients with multiple sclerosis.

CONTEXT: Human herpesvirus 6 (HHV-6) has been linked with multiple sclerosis (MS). OBJECTIVES: To determine HHV-6 viral load in patients with MS, and to analyze separately its 2 variants, HHV-6A and HHV-6B. PATIENTS AND METHODS: We analyzed 149 blood and serum samples; 103 were from patients with relapsing-remitting MS (33 during an MS relapse and 70 during remission), and 46 were from healthy blood donors. To determine whether the HHV-6 genome and its variants were present, we analyzed viral DNA using quantitative real-time polymerase chain reaction, which has a sensitivity of 1 copy. RESULTS: We found HHV-6 DNA in the peripheral blood mononuclear cells of 53.4% of patients and 30.4% of healthy blood donors; HHV-6A was found in 20.4% of patients and 4.4% of controls, and HHV-6B was found in 33.0% vs 26.1%, respectively. Mean viral load in both groups was 7.4 copies of HHV-6 per microgram of DNA (range, 1-15 copies). Analysis of serum samples showed that none of the healthy blood donors were positive for HHV-6, although 14.6% of patients were positive for the virus, specifically the HHV-6A variant. There was no difference between patients during remission or relapse. Mean viral load was 26.3 copies/microg microgram of DNA (range, 1-86 copies). CONCLUSIONS: Despite the low viral load and the lack of clinical correlation, and given the biological characteristics of the virus, our results suggest that there was active HHV-6A infection in 14.6% of patients with MS. Further quantitative real-time polymerase chain reaction studies will help us understand the clinical significance of such a low viral load.