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

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.

Integrated analyses of single-cell atlases reveal age, gender, and smoking status associations with cell type-specific expression of mediators of SARS-CoV-2 viral entry and highlights inflammatory programs in putative target cells

“…One intriguing possibility is that encephalitis might arise as an autoimmune response to myelin antigens expressed by infected cells. Antibodies against peptides of myelin proteins have been clinically shown to be associated with autoimmune encephalitis and seizures [132][133][134] , and myelin peptides are targets of T cells 135 in demyelinating inflammatory neurological diseases such as acute demyelinating encephalomyelitis, Guillain-Barre Syndrome, and multiple sclerosis [135][136][137][138][139][140][141][142] . Oligodendrocytes, the myelin-producing cells of the CNS, are the main ACE2 + TMPRSS2 + cell type in the brain, the myelin transcriptional regulator MYRF was enriched in certain ACE2 + TMPRSS2 + cell types as noted above, and myelin proteins MOG and MBP were coexpressed in numerous ACE2+ clusters across organs.…”

Molecular mimicry, genetic homology, and gene sharing proteomic “molecular fingerprints” using an EBV (Epstein-Barr virus)-derived microarray as a potential diagnostic method in autoimmune disease

“…Using proteomic technology, hundreds or even thousands of epitopes can be analyzed simultaneously with a single serum sample. Detailed mapping of autoreactive viral epitopes could suggest epitopes capable of differentiating healthy patients versus patients with autoimmune syndromes such as SLE and scleroderma in which EBV reactivation, EBNA-1, and ZEBRA expression are evident [17][18][19].…”

Viruses and endogenous retroviruses in multiple sclerosis: From correlation to causation

“…44 Conversely, patients with IM showed activation of MOG-specific memory B cells. 45 Furthermore, EBV genetic material has been identified in the CSF and perivenular infiltrates of brain and spinal cord white matter, and, more recently, in the cortical grey matter and cervical lymph nodes of patients with MS. 44,46 EBV brain infection is likely to be limited to only a small number of B cells (approximately 5-3000 per 10 7 memory B cells). 23,47 This could explain why histological studies for their detection are difficult, and it underscores the need for technologies such as massively parallel single-cell sequencing to detect these rare events in the future.…”