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Molecular basis identified for tissue specific immune regulation in the eye and kidney
Date:2/20/2013

Both AMD, which affects around 50 million people worldwide, and aHUS, a rare kidney disease that affects children, are associated with incorrectly controlled immune systems. A protein called complement factor H (CFH) is responsible for regulating part of our immune system called the complement cascade. Genetic alterations in CFH have been shown to increase a person's risk of developing either AMD or aHUS, but rarely both. Why this is the case has never been explained until now.

Researchers from the Wellcome Trust Centre for Cell Matrix Research and the Ophthalmology and Vision Research Group in The University of Manchester's Institute of Human Development have been expanding on their previous work that demonstrated a single common genetic alteration in CFH prevents it from fully protecting the back of the human eye. The research teams of Professor Tony Day and Professor Paul Bishop found that a common genetically altered form of CFH associated with AMD couldn't bind properly to a layer under the retina called Bruch's membrane. Having a reduced amount of CFH in this part of the eye leads to low-level inflammation and tissue damage, eventually resulting in AMD.

However, this mutation that changes CFH function in the eye has no affect on the protein's ability to regulate the immune system in the kidney. A cluster of genetic mutations in a completely different part of CFH are associated with the kidney disease aHUS, but these have no affect on the eyes.

In their most recent study, which was funded by the Medical Research Council and published in the Journal of Immunology, the Manchester researchers have identified why these mutations in CFH result in diseases in very specific tissues. Professor Day explains: "For the first time we've been able to identify why these protein mutations are so tissue specific. We're hoping our discovery will open the door to the development of tissue specific treatments to help the millions of people
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Contact: Morwenna Grills
Morwenna.Grills@manchester.ac.uk
44-161-275-2111
University of Manchester
Source:Eurekalert

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