DNA changes in pediatric MS point to possible role for Epstein-Barr virus
Researchers identified 55 DNA methylation regions that differed from controls
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DNA methylation is an epigenetic mechanism that can affect how genes are regulated without changing the underlying genetic code. A new study found distinct DNA methylation patterns in children and adolescents with pediatric-onset MS compared with controls. (Image from iStock)
- Children and adolescents with pediatric-onset multiple sclerosis exhibit distinct DNA methylation patterns compared to healthy controls.
- These epigenetic changes were linked to Epstein-Barr virus infection and immune-related pathways, with EBV infection emerging as the top-ranked pathway.
- Further research is needed to determine how these DNA methylation changes relate to EBV and other environmental exposures in pediatric multiple sclerosis.
In children and adolescents with multiple sclerosis (MS), chemical changes that can influence how genes are switched on or off differ from those seen in young people without the disease, a new study found.
These changes, known as DNA methylation, were found in regions of DNA containing genes linked to several biological pathways, including those associated with Epstein-Barr virus (EBV) infection, a well-established risk factor for MS.
The researchers cautioned that the study cannot prove cause and effect, but their findings suggest EBV may play a role in the biological changes linked to pediatric MS.
Epigenetic changes may link environmental and genetic risks
“Our findings align with recent evidence highlighting how environmental triggers and genetic risk factors converge on shared epigenetic pathways leading to MS onset. This supports the hypothesis that DNA methylation serves as a critical regulatory interface between early exposures and the [pediatric-onset MS] immune profile,” the scientists wrote.
The study, “Epigenetic Insights in Pediatric Multiple Sclerosis: DNA Methylation Highlights an Involvement of Epstein-Barr Virus Infection and Host Immune Networks,” was published in Neurology Neuroimmunology & Neuroinflammation.
MS is an inflammatory disease that causes damage to the brain and spinal cord. Although it usually begins in adulthood, it can also begin during childhood or adolescence. This is called pediatric-onset MS (POMS).
The causes of MS are not fully understood, but both genetic and environmental factors are thought to contribute to disease risk. Infection with EBV, the virus that causes infectious mononucleosis, or mono, is one of the strongest known risk factors for MS.
However, EBV infection is extremely common, and only a small proportion of infected people develop MS. Differences in genetic susceptibility and other factors may help explain why.
When scientists study genetic risk factors, they traditionally focus on the genetic code itself. But the DNA sequence is only part of the picture. Epigenetic mechanisms can affect how DNA is packaged and read by cells, changing how genes are regulated without altering the underlying genetic code.
One such mechanism is DNA methylation, which involves adding chemical groups called methyl groups to DNA. Depending on where this occurs, methylation can affect whether a gene is active and how active it is. DNA methylation patterns can be affected by both genetic and environmental factors.
Study compared DNA methylation in pediatric MS and controls
In this study, researchers investigated whether DNA methylation patterns differ in young people with POMS compared with those without the disease. They analyzed blood samples from 122 children and adolescents with POMS and 53 children and adolescents without the disease, all from Italy.
The team identified 55 differentially methylated regions (DMRs) — areas of the genome that showed significantly more or less DNA methylation in POMS patients compared with controls.
The strongest signals involved several genes, including CHI3L2, LPCAT1, CD19, PARP1, CPT1B-CHKB, and IGF2R. Some of the identified regions overlapped with genetic locations previously associated with MS.
The scientists then conducted computer-based analyses to look at biological pathways associated with the affected genes. EBV infection emerged as the top-ranked pathway.
“EBV infection emerged as the top-ranked term in the primary analysis and it was confirmed in the sensitivity analysis,” the researchers wrote.
The results point to a potential connection between EBV-related biological pathways and the DNA methylation changes observed in POMS. However, the study cannot establish cause and effect.
Most participants with available EBV testing in both groups had evidence of previous infection. However, the researchers found that the EBV-related signal was still present regardless of participants’ prior EBV infection status.
The researchers said further studies are needed to confirm the findings and better understand how the observed methylation patterns relate to environmental exposures.
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