Autoimmune diseases tend to ease up during pregnancy, and for women with multiple sclerosis, physicians have documented fewer relapses of the condition while women are pregnant compared to before and after having a baby. Anecdotally, many MS patients also feel better when they’re expecting. Researchers believe that this happens because during pregnancy, the body reins in its immune response so as to not reject the fetus—and in doing so counteracts autoimmune diseases. But as to how exactly this all works, scientists are uncertain.
“Obviously, everybody would love to understand why it happens because if you could bottle that property of pregnancy, perhaps you could use it therapeutically,” Adrian Erlebacher, a reproductive immunologist at the University of California, San Francisco, tells The Scientist.
To investigate why this happens in pregnant women with multiple sclerosis (MS), Stefan Gold, a neuroscientist at the Institute of Neuroimmunology and Multiple Sclerosis at the Universitätsklinikum Hamburg-Eppendorf, in Hamburg, Germany, and colleagues examined T cell populations in 11 MS patients before, during, and after pregnancy and in 12 women without MS during and after pregnancy. They categorized the T cells into different groups based on a genetic analysis of the cells’ receptors.
In the first trimester, they found, MS patients’ T cells were dominated by just a few types, called clones, each with a different T cell receptor. Between the first and third trimesters, those dominant clones declined in abundance, and T cells became more evenly distributed across the different populations, Gold says. In women without MS, the pregnancy-associated changes in the T cell repertoire were not significant. Gold and his colleagues reported their results in Cell Reports on October 22.
“Pregnancy doesn’t shut down the entire immune system. It just selectively reduces a couple of dozen out of thousands and thousands of clones that are presumably associated with driving this autoimmune immune attack,” says Gold.
Next, Gold and his team identified so-called candidate clones whose numbers varied with relapse risk around the time of pregnancy, dropping in abundance between trimesters one and three, then rebounding after pregnancy.
The candidate clones that fit this profile were different for each MS patient, but this did not surprise Gold. “If there was one particular T cell clone that was present in all MS patients and [in] nobody who doesn’t have MS, we would have found that clone 30 years ago,” he says.
This could prove to be a new form of add-on therapy.—Yara Fragoso, Universidade Metropolitana de Santos
The patient with the highest number of candidate clones had 40. She also had an MS relapse three months after giving birth. The researchers found that 23 of her candidate clones were also among the most common clones present during her relapse. Because of this overlap, the authors believe that the candidate clones may be the same ones that cause MS flares.
“They observe that certain immune cells disappear during pregnancy only to reappear after delivery, after the end of pregnancy. And they suspect, and I think this is a reasonable assumption, that these particular cells that disappear during pregnancy but reappear after pregnancy are critical or crucial in the pathogenesis of MS,” Reinhard Hohlfeld, a neurologist and neuroimmunologist at the Ludwig Maximilians University of Munich who was not involved in the work, tells The Scientist.
The researchers also tested how the woman’s T cells reacted to several MS-associated proteins, including myelin proteins. They found that the T cells that responded to myelin and Epstein-Barr virus, both of which are thought to have roles in MS pathogenesis, did not change in frequency over the course of pregnancy.
“This study surprisingly shows that in the situation where the disease gets better, which is in pregnancy, that the T cells that are thought to drive the disease previously are not the ones that are changing, that there are instead other T cells that are changing,” says Erlebacher, who was not involved in the work.
One future clinical application of the work would be to track T cell populations in MS patients when they become pregnant and then target the T cells that decrease in frequency during pregnancy in personalized therapies, Gold says.
“This could prove to be a new form of add-on therapy,” Yara Fragoso, who studies MS at the Universidade Metropolitana de Santos in Sao Paulo, Brazil, and was not involved in the work, tells The Scientist in an email.
Gold’s long-term goal is to identify the mechanism by which the body downregulates only certain T cells during pregnancy and harness that as an MS treatment. He is currently analyzing the transcriptomes of T cells from the cohort of MS patients in the study in hopes of identifying molecular switches that distinguish the downregulated clones from the others.
“We want to find out what the molecular switches are that make these few clones go down and the other ones not and then develop new therapeutic approaches that would do the same thing, even in people who are not pregnant,” Gold says.
C. Ramien et al., “T cell repertoire dynamics during pregnancy in multiple sclerosis,” Cell Reports, doi:10.1016/j.celrep.2019.09.025, 2019.
Ashley P. Taylor is a New York–based freelance reporter. Follow her on Twitter @crenshawseeds and read her work at ashleyptaylor.com.