Pregnancy is beneficial for women with multiple sclerosis

Researchers have shown that the positive immune system modifications that typically occur during pregnancy help women with multiple sclerosis (MS) temporarily improve when pregnant. 

A particularly unique condition from an immunological perspective is pregnancy. The immune system protects us from harmful toxins. The mother’s immune system does not reject the father’s genetic material, even though it makes up half of the fetus’ genetic makeup. 

The mother’s immune system is evolved to become more tolerant during pregnancy, which is why this balancing act always succeeds.

This discovery might result in improved disease therapies. In MS (multiple sclerosis), an autoimmune condition affecting nerve function, the immune system targets the fat surrounding nerve fibers. It acts as an insulating sheath, causing nerve damage. Most MS patients get worse over time despite new therapy options.

According to the researchers, the brief suppression of the immune response may account for why pregnant women with MS feel better. Relapses, or periods of symptoms, diminish by 70% in the latter third of pregnancy. Other autoimmune conditions, like rheumatoid arthritis, are also affected by this phenomenon and may momentarily improve while a woman is pregnant.

This is why the researchers behind this study wanted to look into what pathways might be important for decreasing symptoms during pregnancy as a first step towards developing future treatment techniques that have the same effect in MS and possibly other related disorders.

The researchers identified genes employed in T cells at various periods throughout pregnancy. They analyzed alterations governing gene switching on and off, specifically DNA methylation, to understand better the mechanisms underlying the decrease in symptoms during pregnancy. A pregnant woman with MS has an immune system similar to that of a healthy pregnant woman.

The researchers discovered networks of interacting genes that are impacted during pregnancy and are linked to the disease and crucial immune system activities. The most significant increases in T cells correspond to the greatest improvement in relapse frequency, with the most significant changes occurring in the last third of pregnancy, when women with MS benefit the most. These alterations are then reversed following pregnancy when disease activity temporarily increases.

Sandra Hellberg, assistant professor at the Department of Biomedical and Clinical Sciences at Linköping University and one of the researchers behind the study, said, “What was possibly most striking is that we couldn’t find any real differences between the groups during pregnancy, as it seems that the immune system of a pregnant woman with MS looks roughly like that of a healthy pregnant woman. 

The researchers discovered networks of interconnected genes that are altered during pregnancy. Their research demonstrates that these genes are strongly linked to the disease and crucial immune system activities.

Sandra Hellberg said, “We can see that the changes in the T cells mirror the amelioration in relapse frequency. The biggest changes happen in the last third of pregnancy, where women with MS improve the most. These changes are then reversed after pregnancy at the point in time when there is a temporary increase in disease activity. It is important to stress that disease activity after that goes back to what it was before the pregnancy.” 

The network of genes impacted during pregnancy also included genes regulated by pregnancy hormones, primarily progesterone. The researchers are currently studying different hormones in the lab to understand better the mechanisms underlying this behavior.

This study results from a long-standing partnership between medical and bioinformatics specialists. Understanding the vast amount of data by analyzing it using network analysis, developed over many years by, among others, a research group directed by Mika Gustafsson at Linköping University, has been a crucial aspect of the project. 

Network analysis is a technique for identifying genes that interact heavily with the genes of interest to the researchers. Other genes in the network are frequently found to be abnormally regulated, affecting crucial processes in disease.

Mika Gustafsson, professor of Bioinformatics, now making the analysis available to other researchers through a newly founded company, said, “Such insights can be used to find alternative medication and new biomarkers to differentiate between subgroups of a disease. We have used this strategy successfully for analysis in research into, for instance, allergy and multiple sclerosis.” 

The study was conducted in collaboration with Linköping University, the Karolinska University Hospital in Solna, Linköping University Hospital, Länssjukhuset Ryhov in Jönköping, and Region Kalmar.

The study was funded by the Swedish Foundation for Strategic Research, the Swedish Research Council, NEURO Sweden, the Swedish Foundation for MS Research, Region stergötland, Linköping University, and others.

Journal Reference:

1. Zenere, A., Hellberg, S., Papapavlou Lingehed, G. et al. Prominent epigenetic and transcriptomic changes in CD4+ and CD8+ T cells during and after pregnancy in women with multiple sclerosis and controls. Journal of Neuroinflammation. DOI: 10.1186/s12974-023-02781-2