When a new life begins to grow in the mother’s womb, the immune system must perform a demanding balancing act: it must tolerate the foetus, which is genetically half-foreign, and at the same time protect the mother from infection.
For most pregnant women, this happens without any problems.
However, for women with autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus, pregnancy puts the immune system under extra strain. This can lead to an elevated risk of pre-eclampsia, premature birth and miscarriage.
The immune system – cell by cell
“Autoimmune diseases vary greatly, and patients react differently to both the disease and the treatment. Many people have to try several medications before finding one that works for them. That is why there is a great need for biological markers that can enable more personalized treatment, including during pregnancy,” said Hilde Julie Tokle Lien, a postdoctoral fellow at the Norwegian University of Science and Technology (NTNU’s) Department of Clinical and Molecular Medicine.
She recently completed her doctoral thesis in which she investigated how the immune systems of pregnant women with rheumatoid arthritis and lupus actually behave during pregnancy – cell by cell.
If left untreated, these diseases react very differently to pregnancy: rheumatoid arthritis patients often experience an improvement, while lupus patients have an elevated risk of deterioration.
To identify the causes at the immune cell level, Lien collaborated with a multidisciplinary team of immunologists, bioinformaticians, doctors and nurses, who collectively carried out advanced analyses of gene activity in individual cells.
A completely new method has also been developed that can be used in further research.
Need for follow-up in the postnatal period
The initial results show clear immunological differences between pregnant women with lupus, pregnant women with rheumatoid arthritis, and healthy pregnant women – particularly in terms of which immune cells dominate.
This occurs even though the women receive excellent follow-up and experience minimal changes in disease activity throughout their pregnancy.
In women with lupus, the differences also persist after childbirth.
“This emphasizes the need for close follow-up during the postnatal period. This is a phase that has traditionally received less attention in rheumatological treatment,” explained Lien.
Important to continue taking medication
Lien and the research team are now working to understand whether the differences are due to changes in gene activity or in how many different types of cells are present. Research is also being conducted into why patients with the same diagnosis can experience such different symptoms, and which factors trigger changes in disease activity.
“Internationally, there is still considerable variation in the use of medication during pregnancy. Although we know that untreated disease generally poses the greatest risk, many women are reluctant to take medication while they are pregnant. It is important to continue taking the medication during pregnancy,” concluded Lien.
Samples and clinical data used in the study were collected by the Norwegian National Advisory Unit on Pregnancy and Rheumatic Diseases (NKSR).