Boosting Immune Tolerance May Offer Protection Against Pregnancy Loss

A new study from the Robinson Research Institute at the University of Adelaide is offering new hope for people who have experienced early pregnancy loss.

In a pre-clinical animal study, published in the American Journal of Pathology , Professor Sarah Robertson and team found a potential protection against pregnancy loss, a common condition affecting natural conception and women undergoing IVF treatments.

The study focused on a specialised immune cell subset called regulatory T cells (Treg cells), which are essential for preparing the uterus for receptive embryo implantation.

“Repeated losses can be devastating and exert a major impact on women, their partners, and society more broadly. An imbalance in the female immune response is implicated in many cases,” said Professor Robertson.

Professor Robertson said previous studies have found low numbers of Treg cells in women who experienced early pregnancy loss, and that they often exhibit changes that lead Treg cells to have functional problems that are reminiscent of autoimmune diseases.

“This can impair the implantation process and suppress development of the early placenta,” she said.

“Therefore, Treg cells provide an attractive target for interventions to improve maternal immune tolerance and protect against pregnancy disorders caused by immune imbalance in at-risk women.

“Our most recent study showed a novel immune intervention called interleukin-2 offers potent protection against pregnancy loss and allows healthy offspring to be born.

“Interleukin-2 has been developed for use in autoimmune conditions with a specific formulation to ensure its effects are targeted directly to the Treg cells.

“When used at a low dose and formulated correctly, the IL-2 shows particular benefit for stimulating expansion of Treg cell populations in the uterus.”

Professor Robertson said while the study demonstrates the potential of targeting Treg cells and provides pivotal evidence to justify human studies, it is not yet ready for clinical use. 

“It will be important to undertake clinical trials to assemble evidence of safety and benefit in human subjects before the treatment can be recommended,” she said

Reference: Foyle KL, Chin PY, Merkwirth C, et al. IL-2 complexed with anti–IL-2 antibody expands the maternal T-regulatory cell pool and alleviates fetal loss in abortion-prone mice. Am J Pathology. 2024;194(11):2128-2149. doi: 10.1016/j.ajpath.2024.07.012

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