Infectious Mononucleosis Triggers Generation of IgG Auto-Antibodies against Native Myelin Oligodendrocyte Glycoprotein.

Kristina Kakalacheva,Silke Wiesmayr,Tarik Azzi,Jan Lünemann,Christian Münz,Fabienne Brilot,Stephan Regenass,Russell Dale,David Nadal,Christoph Berger,Kevin Rostasy

doi:10.3390/v8020051

Abstract

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

Highlights

Epstein-Barr virus (EBV) is a gamma-herpesvirus that establishes a benign, lifelong infection in resting memory B cells in over 90% of the human population worldwide
We found that infectious mononucleosis (IM) patients from both cohorts showed higher total serum immunoglobulin M (IgM) and IgG levels as compared to controls (Figure 3A)
IgM antibodies specific for autoantigens have previously been described to occur frequently during acute IM, to be highest soon after onset and to disappear during convalescence [14,15,16]

Summary

Introduction

Epstein-Barr virus (EBV) is a gamma-herpesvirus that establishes a benign, lifelong infection in resting memory B cells in over 90% of the human population worldwide. About 50% of the population acquires EBV between one and five years of age, while another large percentage contracts the virus during adolescence [1]. EBV in the second life decade or later, manifest symptomatic primary infection, known as infectious mononucleosis (IM) [2]. EBV infection, and in particular a history of IM, have been associated with the development of autoimmune diseases [3]. Several well-controlled epidemiological studies confirmed that a history of IM is associated with an approximately two-fold increased risk to develop multiple sclerosis (MS) later in life [3,4]. EBV seropositivity occurs more frequently in patients with systemic lupus erythematosus (SLE) compared to demographically matched healthy controls [5] and juvenile forms of these diseases appear to be associated with EBV [6,7]

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Results

Conclusion