Doctors could PREDICT premature births after study shows women have an ‘immune clock’ during pregnancy

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Lead author Dr Brice Gaudilliere said: ‘Pregnancy is a unique immunological state.

‘We found that the timing of immune system changes follows a precise and predictable pattern in normal pregnancy.

‘Ultimately, we want to be able to ask, “Does your immune clock of pregnancy run too slow or too fast?”‘ 

Postdoctoral fellow Nima Aghaeepour, an instructor in anesthesiology, perioperative and pain medicine, said: ‘It’s really exciting that an immunological clock of pregnancy exists.

‘Now that we have a reference for normal development of the immune system throughout pregnancy, we can use that as a baseline for future studies to understand when someone’s immune system is not adapting to pregnancy the way we would expect.’

Earlier studies suggested that inflammatory immune responses may help trigger early labour.

If scientists identify an immune signature of impending preterm birth, they should be able to design a blood test to detect it.

The study used blood samples collected from 18 women who had full-term pregnancies.

Each woman gave four samples, one during each of the three trimesters of pregnancy, and one six weeks after delivery.

Samples from an additional 10 women with full-term pregnancies were used to validate the findings.

The researchers used mass cytometry to simultaneously measure up to 50 properties of each immune cell in the blood samples.

They counted the types of immune cells, assessed what signalling pathways were most active, and determined how they reacted to being stimulated with compounds that mimic infection with viruses and bacteria.

With an advanced statistical modelling technique, introduced for the first time in this study, they described in detail how the immune system changes during pregnancy.

Instead of grouping the samples by trimester, the model treated gestational age as a continuous variable.

This allowed the researchers to account for the exact time during pregnancy when each sample was taken.

The study confirmed immune features of pregnancy already known, such as natural killer cells having enhanced action.

The researchers also uncovered several features of how the immune system changes.

This included activity of the STAT5 signalling pathway in CD4+T cells increasing during pregnancy on a precise schedule, reaching higher levels than normal people.

The STAT5 pathway is involved in helping another group of immune cells, regulatory T cells, to differentiate.

Earlier research in animals suggests that regulatory T cells are important for maintaining pregnancy.

The next step will be to use blood samples from mothers who give birth prematurely to see where their trajectories of immune function differ, the researchers concluded.

Prof Gaudilliere said: ‘We’re especially interested in understanding more precisely what is happening very early and very late in pregnancy.

‘We’d like to see if there is really a switch we can catch, a sweet spot where deviation from the norm would be maximal with pathology.’

Dr Aghaeepour said: ‘The immune system does not act in isolation, and we’re now very interested in profiling its interplay with other aspects of mothers’ biology, such as their genetics, metabolism and the body’s microbial communities to come up with a holistic biological clock of pregnancy.’

The study was published in the journal Science Immunology.

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