Study: DNA Methylation in T-cells Affected by MS and Its Treatments

Multiple sclerosis (MS) is characterized by changes in methylation — a type of chemical modification in the DNA that changes how genes are read — in immune cells called T-cells, according to a new study.

The results also suggest that treatments for MS can help to normalize methylation patterns.

“These findings indicate an important role for DNA methylation of T cells in MS pathological processes and provides further evidence for a link between the environment and genetic makeup through DNA methylation,” the researchers wrote.

The study, “Global DNA methylation changes in treated and untreated MS patients measured over time,” was published in the Journal of Neuroimmunology.

Methylation basically involves attaching a small chemical tag — a methyl group — to a molecule of DNA. This kind of modification alters how the genes are read, or what genes are turned “on” and “off,” and to which extent. How the genes are read can have profound effects on the activity of cells.

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Broadly, adding methyl groups tends to “turn off” a piece of DNA, but the details of these processes are only beginning to be understood. Methylation is a form of epigenetic modification, a broader term for alterations to DNA molecules that don’t change the sequence of the genetic code.

Here, a group of scientists in Norway conducted methylation analyses on T-cells taken from 35 patients with relapsing-remitting MS, and 10 people without the disease; all participants were female. T-cells are a type of immune cell that is critical for fighting infections, and also are thought to play a central role in driving MS-causing inflammation.

Samples were taken and analyzed at two points in time, several years apart. All of the MS patients were untreated when the first sample was taken, but at the time of the second sampling, 20 of them (57%) had started treatment with a disease-modifying therapy (DMT), a medication that has been proven to slow the course of the disease.

Notably, there were differences in the follow-up time among groups. Specifically, for patients treated with a DMT, the time between the first and second sample collection was markedly shorter than for untreated patients or healthy participants.

With these data in hand, the researchers conducted statistical analyses to look for patterns in how DNA methylation in T-cells changed over time.

The results broadly showed that MS patients had a greater increase in methylation over time, compared with the participants without the disease. Moreover, the increase in methylation was larger for MS patients who had not been treated with a DMT, compared with treated patients.

“We found that the genome-wide DNA methylation profiles in T cells from MS patients exhibited significant changes over time. The treated MS patient group showed fewer significant DMPs [methylated regions of DNA] between the visits compared to the untreated MS patients,” the researchers concluded.

“Our study suggests that the genome-wide DNA methylation landscape of MS patients is affected both by medications and the presence of MS itself,” they added.

The team stressed that this is a small study, and it’s impossible to rule out that other differences among the participants could have contributed to the results. They noted a need for further research with more uniform sampling, as well as a need to investigate the methylation-related effects of specific DMTs.