Epstein-Barr Virus in Multiple Sclerosis
MP Toscano, C Cohen, SB Hunter. Emory University, Atlanta, GA
Background: Multiple sclerosis (MS) is a chronic disease of the central nervous system thought to be autoimmune in nature, and characterized by inflammation and demyelination. Many viruses have been implicated in the pathogenesis of MS, including Human Herpes Viruses 6, 7, and 8, and Varicella Zoster Virus, but follow up studies have failed to confirm a role. Recent evidence has suggested Epstein-Barr Virus (EBV) as a candidate. MS patients have a higher incidence and higher titers of anti-EBV antibodies compared to controls. In addition, some T cells in MS patients can cross-react with both myelin basic protein and virus-derived peptides. EBV has the ability to latently infect B cells, which express specific EBV-associated proteins depending on the phase of infection, including latency membrane protein 1 (LMP1). In a recent study (Serafini et al., J Exp Med. 2007; 204: 2899), positive immunohistochemical (IHC) staining for LMP1 was found within demyelinated lesions in 18 of 20 postmortem specimens from MS patients. EBV-encoded RNA (EBER) was also detected by in-situ hybridization (ISH) in 19 of 20 of these specimens. The EBV immunostaining was mainly located in perivascular lymphocytic cuffs within white matter lesions. The goal of this study is to confirm these findings.
Design: We studied 17 formalin-fixed, paraffin-embedded MS lesions (16 surgical, 1 autopsy) for evidence of EBV infection. Control cases consisted of brain tissue from 15 inflammatory non-MS lesions (11 encephalitis, 4 progressive multifocal leukoencephalopathy (PML)) and from 12 autopsy cases with no histologic abnormalities. IHC was performed using monoclonal LMP1 antibody (Dako, Carpinteria, CA), and ISH was performed using an EBER probe (Ventana Medical Systems, Tucson, AZ). Positive controls included an RNA control on each case as well as Hodgkin's and non-Hodgkin's lymphomas. Negative controls were performed on all cases without antibody or probe.
Results: All MS and control cases were negative for EBV by both LMP1 IHC and EBER ISH. Positive controls showed strong diffuse positive staining by both IHC and ISH. Negative controls showed no staining with minimal background.
|MS||0/17 (0%)||0/17 (0%)|
|Encephalitis||0/11 (0%)||0/11 (0%)|
|PML||0/4 (0%)||0/4 (0%)|
|Normal Control||0/12 (0%)||0/12 (0%)|
Conclusions: The results of this experiment do not confirm previously reported evidence for a role of EBV infection in multiple sclerosis.
Monday, March 9, 2009 9:30 AM
Poster Session I Stowell-Orbison/Autopsy Award # 223, Monday Morning