Epstein-Barr virus may drive MS by dysregulating certain immune cells
Cells in neck lymph nodes show abnormal activity, reactions against EBV: Study
In the lymph nodes of the neck of people with multiple sclerosis (MS), certain immune cells show abnormalities in activity and signs of reactions against the Epstein-Barr virus (EBV), a new study reports.
The findings may help to explain the connection between MS and EBV, researchers said.
The study, “Altered immune landscape of cervical lymph nodes reveals Epstein-Barr virus signature in multiple sclerosis,” was published in Science Immunology.
The Epstein-Barr virus is well-known for causing infectious mononucleosis, colloquially known as mono. EBV can also infect people and cause nonspecific symptoms or no symptoms at all, so while most adults have been infected with the virus, the majority does not know they have it.
EBV infection key risk factor for MS
A building body of evidence has suggested EBV infection is a key risk factor for MS. In fact, some data suggest MS can only develop in people who have a history of EBV infection. However, it remains unclear exactly how EBV may set the stage for MS.
To better understand the interaction between EBV and MS, researchers conducted detailed analyses of immune cells extracted from lymph notes in the neck. The analysis included lymph nodes from seven people with newly diagnosed MS and six people who did not have MS.
Lymph nodes are immune organs — if immune cells are the body’s soldiers, the lymph nodes are like barracks where immune cells live and train to do battle. The researchers specifically focused on lymph nodes of the neck because part of the immune response against EBV seems to occur in that location, so they’re most likely to play roles in MS.
The researchers found MS patients showed marked abnormalities in their B-cells, the immune cells that make antibodies, which have been heavily implicated in the development of MS. Specifically, MS patients had more memory B-cells, which are B-cells that are produced after infection to help the body fight off the same infection if it occurs again. At the same time, patients had fewer germinal center B-cells, which are basically B-cells that are actively involved in fighting infection.
“Our findings indicate a significant disturbance in B cell maturation in [neck lymph nodes] of [people with] MS compared with those of healthy controls,” the researchers wrote.
Notably, EBV is able to infect B-cells and alter their activity. This has been hypothesized to be one of the main mechanisms that might link EBV and MS. Supporting that idea, the abnormal memory B-cells in MS patients showed changes in genetic activity that are similar to what’s seen when EBV infects these cells. The researchers also found more DNA from the Epstein-Barr virus in lymph nodes from people with MS than in those without the disease.
“Paralleled with the detection of an EBV signature and the known influence of EBV [on B-cell activity], our findings support B cell dysregulation as a central mechanism in MS pathogenesis [disease development],” the researchers wrote.
Abnormalities found in B-cells, CD8 T-cells
In addition to changes in B-cells, the researchers also noted abnormalities in CD8 T-cells from some of the MS patients. CD8 T-cells are considered the assassins of the immune system, able to kill other cells that show signs of viral infection. Each CD8 T-cell is equipped with a specialized receptor that it uses to attack one specific target.
The researchers found a few of the MS patients had increased levels of CD8 T-cells targeting EBV. The highest numbers of anti-EBV CD8 T-cells were detected in a patient who had their lymph node sample collected during a disease relapse, where MS symptoms flare up due to increased inflammation.
Analyses of blood samples showed EBV-targeting CD8 T-cells were also present in the blood of patients who had these cells in their lymph nodes, implying that the EBV-attacking CD8 T-cells can move out of the lymph nodes to other parts of the body.
Collectively, these data suggest EBV may lead to dysregulation of B-cells and CD8 T-cells in MS patients, which may set the stage for MS-driving inflammation. Based on the available data, the researchers think that B-cells dysregulated by EBV may trigger a surge in activity of anti-EBV CD8 T-cells, which can move to the brain to trigger inflammation.
“We hypothesize that EBV-reactivated B cells expand in [lymph nodes] before a relapse, triggering an expansion of EBV-targeting memory CD8 T cells and their subsequent migration to the [brain and spinal cord], leading to a relapse,” the scientists wrote.
They stressed, however, that this hypothesis was based on observations from a few patients, so more work is needed to validate this idea.
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