The research team looked at the two parts of CFH affected by the mutations. Both regions are capable of recognising host tissues, through interacting with sugars called glycosaminoglycans (GAGs). Successfully recognising these GAGs lets CFH build up a protective layer on the surface of our tissues that prevents our own immune system from attacking them.
It had always been believed that the region with mutations associated with aHUS was the most important for host recognition and for years people have been researching how to readdress immune dysregulation based on this belief. However, the recent discovery of a single common genetic alteration in the other part of CFH that is associated with eye disease raised the possibility that this previous opinion was not fully accurate.
The Manchester researchers compared the way the different regions of the protein interacted with eye tissue and kidney tissue. They discovered that the region of CFH that helps protect the kidney had no effect in the eye. Instead the other part of CFH, which is subject to the AMD-associated genetic alteration, was fundamentally important in protecting the eye, but this region did not contribute to the binding of CFH to kidney tissue.
Their findings show, for the first time, that the level of importance of the two regions of CFH changes depending on which tissue the protein finds itself. This specificity appears to be mediated by the presence of different populations of GAGs.
Dr Simon Clark says: "Our findings suggest that the particular structure within the eye and kidney tissue determines precisely how and where CFH will bind. It's as if the tissues have their own molecular postcodes."
He continues: "We're very pleased to be able to show why mutations in CFH are so tissue specific. This is important because if we're going to improve treatments for devastating diseases, such as AMD, we need to be able to dev
|Contact: Morwenna Grills|
University of Manchester