Nov 13 2007
The placenta uses a cloaking device similar to that used by parasites to avoid detection by the mother's immune system. MRC funded scientists looking to develop a diagnostic test for pre-eclampsia, a major and potentially fatal cause of fetal and maternal illness, made the amazing discovery which could have far reaching implications.
The team, based at the University of Reading, believe their findings will revolutionise our understanding of the placenta and research into recurrent miscarriages and pre-eclampsia. It is also hoped this method of avoiding immune rejection could be mimicked and used in other areas such as arthritis or even stem cell therapy.
At the turn of 21 st century Professor Lowry and his team discovered that the small protein neurokinin B (NKB), which is secreted by the placenta, is raised significantly in mothers when pre-eclampsia develops. Because NKB can be detected as early as week 9 of pregnancy it can be used to predict which women are more at risk of the condition, which tends to occur in the second and third trimester.
Phil Lowry led the Reading team: “While looking to translate this discovery into a diagnostic kit we were flummoxed. The placental form of the protein did not react in the same way as the NKB we had been using. It became clear that there was a modification occurring during the synthesis of the protein by the placenta,” says Lowry. “What we found next was most unusual. It appeared the placental NKB contained the molecule phosphocholine which is used by filarial nematodes, a type of parasitic worm, to escape host immune systems! I have had two or three ‘Eureka!' moments in my career. This one, at 63, I am happy to bow out on.”
The human foetus and placenta have a different genotype from the mother. The foetus has been described before as acting in a parasitic way: it avoids rejection by the mother and exerts considerable influence over her metabolism for its own benefit, in particular diverting blood and nutrients. Now it would appear the similarities go much further. Although the mode of attachment of the phosphocoline (PC) is different in the mammalian placenta, its presence is startling.
“When we saw this, our immediate instinct was to look at other proteins in the placenta. So far, from what we have seen, it appears a large number of them possess this protein surface molecule which cloaks them from the host immune system,” Lowry continued.
It is hoped that this breakthrough will have many applications beyond the placenta. Already work is being done to investigate how PC-containing protein segments could help reverse conditions such as rheumatoid arthritis and other autoimmune disorders.
“Devising a mechanism by which you could make cells invisible to the immune system could lead to cures for a number of diseases and conditions. But as many discoveries in science, this presents us with a whole new can of worms. It will provide work for scientists for decades to come no doubt,” concluded Lowry.
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