More evidence for a viral trigger...
Apoptotic effects of Human Herpesvirus-6A on glia and neurons as potential triggers for central nervous system autoimmunity.
J Clin Virol. 2006 Dec;37 Suppl 1:S11-6.
Gardell JL, Dazin P, Islar J, Menge T, Genain CP, Lalive PH.
Department of Neurology, University of California, San Francisco, CA, USA; Neurosciences Unit, California Pacific Medical Center Research Institute, San Francisco, CA, USA.
BACKGROUND: Human Herpesvirus type 6 (HHV-6A and/or HHV-6B) has been tentatively associated with multiple sclerosis (MS). However, there is currently no direct proof of pathogenicity.
OBJECTIVES: To determine whether exposure to HHV-6 variants is capable of inducing programmed cell death (apoptosis) in representative cell types of the central nervous system (CNS).
STUDY DESIGN: HHV-6A and HHV-6B variants were grown on human T cell lines HSB2 and MOLT-3, respectively. Human neuronal (SK-N-SH), astrocytes (CRT), and oligodendrocytes (TC620) cell lines were exposed in vitro to infected T cells in a trans-well system for up to 4 days (5x10(4) cells target cells and 2x10(6) T cells). Apoptosis was measured by a FACS-based method.
RESULTS: Exposure to HHV-6A induced apoptosis in a time-dependent manner, while exposure to HHV-6B did not. Three days after exposure, apoptosis was increased compared to normalized controls, by 239% in neurons, 321% in astrocytes, and 326% in oligodendrocytes, respectively.
CONCLUSIONS: This study provides the demonstration that exposure to immune cells carrying replicating HHV-6A may injure glial cells and neurons by inducing apoptosis, and direct evidence for a causal association between HHV-6A with MS and related disorders.
Clinical parameters and HHV-6 active replication in relapsing-remitting multiple sclerosis patients.
J Clin Virol. 2006 Dec;37 Suppl 1:S24-6.
Alvarez-Lafuente R, Garcia-Montojo M, De Las Heras V, Bartolome M, Arroyo R.
Servicio de Neurologia, Hospital Clinico San Carlos, Madrid, 28040, Spain.
BACKGROUND: Although the etiology of multiple sclerosis (MS) remains uncertain, clinical, epidemiological, and laboratory findings suggest that environmental factors may be involved in the disease.
OBJECTIVE: This study was undertaken in order to investigate the possible relation of human herpesvirus-6 (HHV-6) in relapsing-remitting MS (RRMS).
STUDY DESIGN: A one-year follow-up study was performed analyzing serum samples of 63 patients with RRMS and 63 healthy blood donors (HBD) by a quantitative real time PCR, to measure HHV-6 prevalence and viral load. Clinical data (starting age and EDSS increase) were collected.
RESULTS: (i) We found 25.4% of RRMS patients with at least one positive serum sample along the one year follow-up. (ii) 19.1% of RRMS samples in relapse had HHV-6 active infection vs. 7.9% of RRMS samples in remission. (iii) We only found variant A. (iv) RRMS patients with HHV-6 active replication initiated the disease 1.9 years earlier, and they had a higher EDSS increase.
CONCLUSIONS: A higher HHV-6A frequency of active infection seems to be related with the exacerbations in a subset of RRMS patients. Regarding the relationship between HHV-6A active infection and the clinical data in RRMS patients, further investigations are needed.