Affecting more than 9,000 people in the UK sufferers see their blood vessels - particularly in the kidney and lungs- attacked by their body's own white blood cells, which are supposed to patrol circulation to rid it of harmful invaders. The resulting inflammation can affect any organ but in particular causes kidney, lung and respiratory tract disease.

The researchers tracked down more that 1200 people in the UK and 1400 in Europe who were diagnosed with ANCA-associated vasculitis. Using cutting edge genetic analyses they showed that four genetic variants play a crucial role in causing the condition. All of the genes affected are involved in the body's natural response to infection and injury, and mistakes make the immune system more likely to turn on its own host.

Importantly, the scientists showed that patients with ANCA-associated vasculitis fell into two distinct groups, depending on which genetic variants they carried. In each case the body produces a different molecule, called an autoantibody; the result of which is the immune system turning against its own host.

The discovery is important because it could pave the way for new treatments in the future that could specifically tackle these two different auto immune diseases.

Dr Paul Lyons, Senior Research Associate at the Cambridge Institute of Medical Research (CIMR), one of the leaders of the study said:

''Our study demonstrates for the first time that ANCA-associated vasculitis is not really one condition, but two diseases with different causes hiding under one umbrella. Because the condition is rare this has been difficult to prove until now. Our key finding is that an important difference between two groups is in the genes, and not only in the symptoms we can see.''

The Lee group has developed a new point of care rapid test for Chlamydia trachomatis, which has been evaluated in 3 clinical sites in the UK with excellent results in performance characteristics and ease-of-use features. The test recently received regulatory approval for use in the European Union, thus paving the way for it to enter clinical practice. Ongoing work supported by the BRC is includes the development of rapid Simple Amplification-Based Nucleic Acid Testing (SAMBA-NAT) Systems for both HIV and Avian Influenza.

Therapeutic cancer vaccines are ineffective even though they cause expansion of tumor 'specific T cells, because these T cells are inhibited by the tumor stromal microenvironment in both humans and mice. The Fearon lab depleted stromal cells expressing fibroblast activation protein-alpha (FAP), which are found in all human carcinomas, by administering diphtheria toxin (DT) to a mouse transgenic for the human DT receptor driven by fap transcriptional regulatory elements. This caused frank necrosis of LL2/OVA tumors, supporting the proposed detrimental role for the FAP+ cell in the response to therapeutic vaccines ' work now in press with Science.

This research next aims to determine the signals that cause the development of the FAP+ stromal cell, and the means by which the FAP+ cell causes local immunosuppression. An additional interesting aspect of this cell type is that it exists in normal mice and regulates hematopoiesis and appetite, the former probably via forming the osteoblastic niche and the latter by unknown means.

Pharmacological interruption of either of these processes would be predicted to enhance the efficacy of therapeutic cancer vaccines. Depletion of FAP+ stromal cells also controls the growth of pancreatic ductal adenocarcinomas in the KPC mouse; interesting because this is the best murine model of a human adenocarcinoma. The focus on this stromal cell was prompted by clinical studies of the occurrence of FAP+ cells in human cancers, an autoimmune disease (RA), and chronic tissue repair (cirrhosis).

Therefore, they represent direct interventional extensions of clinical research that was limited initially to correlative analyses in mouse models, but now will be translated back to the clinic.

The Chilvers group has established novel methodology to define the kinetics of neutrophil transit across the lung in man using autologous 111In-labelled neutrophils and 99mTc-labelled red blood cells, demonstrating that more than 95% of neutrophils transit the capillary network rapidly, and that smokers have a greater neutrophil loss compared to severitymatched non-smoking COPD patients.

More recently, NIHR BRC funding has supported the establishment of a method which has allowed the measurement of eosinophil circulating half life in man, something never achieved before. The eosinophil t1/2 is 21 hours (compared to 7 hours for neutrophils) and suggests that early re-circulation occurs, as with lymphocytes. This method should allow them to establish sites of eosinophil destruction in health and disease, to quantify lung uptake in asthma, and to develop a clinically applicable 111In-labelled eosinophil scan.

The BRC has funded a bio-informatics post to support the biomarker discovery programme run by the Smith laboratory, which has resulted in the discovery of a prognostic biomarker which has been patented, published in Nature Medicine, and is soon to enter clinical trials. In addition to the initial findings made in SLE and vasculitis, these findings have been replicated in Inflammatory Bowel Disease and transplantation.

This post, held by Dr Tim Rayner, has also provided the expertise which allowed the initiation of the European Vasculitis Genetics Consortium in Cambridge, and led to the BHF funding the first genome-wide association study in ANCA-associated vasculitis, due for completion in late 2010.

David Jayne has continued an active programme of clinical research in vasculitis and related autoimmune diseases, which has been enabled by the BRC funding his research time. This has, for example, resulted in a definitive paper on the use of Rituximab in the treatment of ANCA-associated vasculitis published in the New England Journal, which will assist in registration of the drug for this indication.