Multiple Sclerosis Research: ResearchSpeak: EBV creating myelin autoimmunity

How does IM trigger autoimmunity in people destined to develop MS? #ResearchSpeak #MSBlog #MSResearch

"The study below finds autoantibodies in people with infectious mononucleosus (IM), which are not found in normal controls. One autoantibody reacts to the myelin protein MOG (myelin oligodendrocyte glycoprotein). The authors suggest that the aberrant immune response that characterises IM may result in autoimmunity. This hypothesis is not new. However, it does not explain the long latency between IM and the clinical onset of MS. If autoantibodies are present as part of acute IM, why don't these people develop MS soon after their acute EBV infection? In addition, anti-MOG antibody response are not all the same and in general are very rare in typical MS. Anti-MOG responses are more common in children with inflammatory demyelination with a clinical picture that tends to mimic neuromyelitis optic, with very prominent spinal cord involvement. I do think this group is on the right track studying IM; we need to explain why people with IM are at increased risk of developing MS. This is one of the grand research challenges in MS. Any ideas would be welcome!"

Kakalacheva et al. Infectious Mononucleosis Triggers Generation of IgG Auto-Antibodies against Native Myelin Oligodendrocyte Glycoprotein. Viruses. 2016 Feb 12;8(2). pii: E51. doi: 10.3390/v8020051

Background: A history of infectious mononucleosis (IM), symptomatic primary infection with the Epstein Barr virus, is associated with the development of autoimmune diseases and increases the risk to develop multiple sclerosis. Here, we hypothesized that immune activation during IM triggers autoreactive immune responses.

Methods: Antibody responses towards cellular antigens using a HEp-2 based indirect immunofluorescence assay and native myelin oligodendrocyte glycoprotein (MOG) using a flow cytometry-based assay were determined in 35 patients with IM and in 23 control subjects.

Results: We detected frequent immunoglobulin M (IgM) reactivity to vimentin, a major constituent of the intermediate filament family of proteins, in IM patients (27/35; 77%) but rarely in control subjects (2/23; 9%). IgG autoantibodies binding to HEp-2 cells were absent in both groups. In contrast, IgG responses to native MOG, present in up to 40% of children with inflammatory demyelinating diseases of the central nervous system (CNS), were detectable in 7/35 (20%) patients with IM but not in control subjects. Normalization of anti-vimentin IgM levels to increased total IgM concentrations during IM resulted in loss of significant differences for anti-vimentin IgM titers. Anti-MOG specific IgG responses were still detectable in a subset of three out of 35 patients with IM (9%), even after normalization to increased total IgG levels. Vimentin-specific IgM and MOG-specific IgG responses decreased following clinical resolution of acute IM symptoms.

Conclusions: We conclude from our data that MOG-specific memory B cells are activated in subset of patients with IM.