Women who have had a miscarriage often read widely on the internet to try to understand what may have been the reason it happened. It is highly likely that they will find something about the possible role of NK cells and various articles about how treatment may improve their chances in a future pregnancy. So what is the real story here?
NK cells are part of the immune system and are found both in the blood (pNK) and in the lining of the uterus (womb) – so called uNK. It seems these two types of NK cells are rather different. NK cells in the blood have a toxic action on foreign insults such as virus’s and tumour cells. In contrast uNK cells do not seem to have these actions – although they do have the ability to stimulate new blood vessel growth (angiogenesis), and it is thought that they are able to impact on how the cells in the developing placenta (the trophoblast) invade and implant in the uterus in the very early stages of a pregnancy.
The interest in NK cells has been boosted by studies that compared women with a history of recurrent miscarriage (RM) and control groups where there was no such history. The studies have suggested that there are increases in both pNK and uNK cells in women who have recurrent miscarriage. The problem with all studies on recurrent miscarriage is how to define it. Unfortunately however many miscarriages are used as the definition, some of the women will have been incredibly unlucky,rather than there being some kind of fundamental problem. So there is a heterogenous population in some of these studies – which can make it difficult to interpret them and as the population is mixed – if there is a real finding to be made it might be diluted.
So what are we to make of the NK story? In August 2011 Tang and colleagues published a systematic review in the international journal Human Reproduction on this subject. This means they looked at all the relevant publications on NK cells – chose the ones they thought were the best according to some predetermined criteria – and pooled the results. Their conclusion was that there was insufficient evidence in the literature to know if there is any value in measuring either pNK or uNK. Furthermore they stated that more studies were needed before measurements of NK cells can be considered as a useful test to determine whether a pregnant women may benefit from immunotherapy. Contrary to what is often thought such systematic reviews are open to bias, but even so the data suggests that in clinical practice there is no justification in measuring NK cells. The logical consequence of this is that using immunotherapy outside the context of a clinical trial is not appropriate.
This does not mean that NK cells are not important. What is clear from the systematic review is that there are insufficient good quality studies from which to form a view. At the moment the data are simply not there. Until we get more information women who make a decision to undergo immunotherapy should be told very clearly that there is no evidence to support its use. Unfortunately for a couple who have been through the experience of several miscarriages, almost any treatment may seem “worth trying” as the alternative of doing nothing is just too difficult to live with. It is essential that clinicians do not exploit such a vulnerable group by offering expensive treatment with little or no prospect of it working. If a couple wants to explore the possibility of immunotherapy it would seem more appropriate to put them in touch with one of the academic centres where NK studies are taking place (for example Professor Siobhan Quenby in Warwick see lecturing in the picture to the left).
The systematic review from Tang and colleagues can be found at this address: http://www.ncbi.nlm.nih.gov/pubmed/21613313