Ontario miscarriage research makes FNAIT breakthrough

There are many reasons why a woman can have a miscarriage. 

But now researchers have made a breakthrough that sheds lights on one cause – and say their findings could mean a new preventative therapy is on the horizon.

The majority of miscarriages are caused by abnormal chromosomes in the foetus which prevents its normal development, according to NHS Choices.

But in some cases, its caused by a potentially very serious condition where the mother’s immune system reacts to her foetus’ cells as if they are foreign invaders and sends antibodies to attack and destroy them.

Researchers have developed a better understanding of one cause of miscarriage – a condition called FNAIT. They hope this could lead to a treatment to prevent pregnancy loss (file photo)

This is called fetal and neonatal alloimmune thrombocytopenia (FNAIT) – and as well as causing miscarriage, in live births it can bring on a bleed on the brain, resulting in lifelong disability or death of the child.

Lead researcher Dr Heyu Ni believes his team have discovered why the mother’s immune system launches an attack.

‘Natural killer cells are normal in pregnancy and necessary for early placental development in humans and other mammals, but their number in placenta should decrease in the late stage of pregnancy,’ he said.

‘In our study, we found that natural killer cells were not decreased, but prevalent and active in cases of FNAIT.’ 

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FNAIT is known to occur in around one in every 1,000 live births – but the true number of women affected is unknown because this figure does not include women with the condition who have miscarriages, say the researchers. 

They estimate 2-3 percent of women are at risk for FNAIT and up to 30 percent of those affected miscarry.

Key findings 

A team from the Keenan Research Centre for Biomedical Science of St Michael’s Hospital in Ontario studied mice, which are biologically similar to humans. 

Scientists already know that natural killer cells – a type of lymphocyte, which are white blood cells in the immune system – have protective effects in pregnancy.

They play a major role in defending the foetus against viruses, disease and developmental issues in the early stages.

But the researchers found that in pregnant mice with FNAIT, their immune response also triggers the activation of more natural killer cells that target cells.

These interact with the father’s proteins, including trophoblasts – cells responsible for the placenta’s development and growth.

This immune attack can cause the placenta to deform and can disrupt the flow of nutrients to the foetus – both of which may limit the baby’s growth in the womb and increase the likelihood of miscarriage.  

Potential new therapies  

The study authors suggest treatment options that might effectively prevent FNAIT-related miscarriages by targeting natural killer cells.

The first is to use intravenous immunoglobulin G (IVIG), a blood product prepared from pools of plasma from more than 1,000 healthy donors. 

IVIG blocks the sensors of natural killer cells, disorienting them and preventing them from targeting placental cells. It also decreases maternal anti-fetal antibodies.

IVIG has already been approved to treat several autoimmune diseases. But to effectively treat FNAIT, it would need to be used in high doses, making it very expensive, notes Dr Ni.

In the lab, the team also tested other therapies, including one targeting cell receptors to block the activation of natural killer cells.

This option is cheaper and may be more efficient than IVIG, said Dr Ni.

While the condition could be combated by removing natural killer cells from the body, this is not recommended because of the essential role natural killer cells play in early placental development.  

More research will be needed to determine whether these new anti-natural killer cell treatments would be effective in humans, said the authors.

‘By understanding what causes reduced growth and miscarriages in FNAIT cases, we are one step closer to being able to identify FNAIT cases early and reduce the rates of the devastating outcomes of this disease,’ said Dr Ni.

The research was published in the journal Nature Communications.