(reprinted from University of Aberdeen magazine, March 2004)
Blood Ties
Researchers at the University of Aberdeen have created a treatment they believe will prevent the tragedy of Rhesus babies. Haemolytic disease of the newborn can happen when mother and baby have particular mismatch of blood types.
If a pregnant woman is one of the 17% who have Rhesus negative blood and her baby is Rhesus positive, and therefore has a compound called D antigen in its blood, the results can be fatal. The D antigen triggers an immune response, attacking her unborn child.
Researchers in Aberdeen have found a way of switching off the immune reaction in mothers, making it possible to create a vaccine. It works in the lab and they plan to set up a spinout company to take the product to clinical trial.
The project is being run in partnership by the University of Aberdeen and the Scottish National Blood Transfusion Service (SNBTS). It is headed by Dr Robert Barker, reader in immunology at the university, and Stan Urbaniak, professor of transfusion medicine at the university and national adviser in immunohaematology to SNBTS.
They have created an entirely synthetic version of the peptide, which switches off the immune response. If it can be developed successfully, it will be a viable and much safer alternative to the current treatment, which uses donated human blood.
"There are several problems with the current product," says Professor Urbaniak. "The first is efficacy, the second is supply - even if it was a perfect product, we're relying on donor blood - and the third is safety."
The pregnant woman will only start making antibodies if the D antigen crosses from the placenta into her blood. This means that she usually only becomes sensitised during childbirth - a fairly blood business - meaning that the first baby would be safe.
But the woman remains sensitised, and, if she becomes pregnant again, her antibodies could cross into the placenta and destroy the foetus's red blood cells.
The reaction can be triggered in a first pregnancy, if there is internal bleeding or through invasive tests such as amniocentesis.
At the moment, the treatment is made from donated human blood. A product called anti-D immunoglobulin is given to the mother within 72 hours of childbirth to destroy the baby's blood cells before they set off the immune reaction. But serious issues surround using donor blood. Britain imports its blood products from the United States because of the slight theoretical risk that UK material might be infected with variant CJD. But recently reported cases of BSE in the US and Europe are casting doubt on whether even these products are risk-free enough.
There's also an issue of donor safety. The anti-D immunoglobulin can only be produced if donors are injected with red blood cells so that their body produces the correct response. This clearly puts the donor at risk of any as yet undetectable infection, such as vCJD - just as HIV and Hepatitis C have been passed on in donor blood.
Professor Urbaniak and Dr Barker won proof of concept funding to test their synthetic material. They have copied the sequence of natural peptide, which appears to switch off the immune response - preventing the woman from becoming sensitised in the first place.
"It's a relatively short peptide, it's simple to make and there's an unlimited supply," says Professor Urbaniak. "It's safer because it's not made from human material. And we're anticipating that like other vaccines, such as rubella, it will last throughout the pregnancy. If we're lucky, we can permanently switch off the response in all at-risk young women and we won't have the problem at all."
Market research indicates that potentially 1.3 million people in the western world could benefit an annual market of $600m. The technique could also be the platform technology for treating other blood disorders.



