Prevention Blood protein profiles provide new insights into large-vessel vasculitis
Large-vessel vasculitis (LVV) is the name for a group of diseases that cause inflammation and damage to arteries (the blood vessels that carry blood away from the heart). LVV affects medium- or large-sized arteries and can lead to serious complications like blood vessel narrowing, blockage, sight loss, aneurysm or stroke. LVV is most often caused by giant cell arteritis (GCA) or Takayasu arteritis (TAK). These autoimmune diseases have traditionally been classified as separate diseases due to differences in the age of patients and the location of the blood vessels affected. However, some experts have recently suggested that GCA and TAK might be variations of the same disease given the difficulty in telling them apart in certain patients. This question has important implications for clinical care and the design of trials testing the effectiveness of new treatments.
Recently researchers from Imperial College including 蓝莓视频 Imperial BRC-funded investigators, the University of Leeds and the University of Oxford published a new paper addressing these questions in the most extensive study of its kind.
The team used new 鈥榩roteomic鈥� technologies to measure the levels of hundreds of blood proteins in nearly 300 patients with GCA or TAK, and a comparison group of unaffected individuals. Application of proteomic technologies involves using technologies for the identi铿乧ation and quanti铿乧ation of overall proteins present in a cell, tissue or organism.
Proteins play a critical role in most biological functions, and proteomics can provide a powerful snapshot or profile of a person鈥檚 or group’s biological state. The team found that the protein profiles in GCA and TAK arteritis were surprisingly similar, indicating a significant overlap in the biology of these diseases. Notably, the shared profiles emphasised the important roles of macrophages鈥攌ey immune cells鈥攁nd structural cells of the artery in LVV. A deeper investigation revealed that the overactivity of these two cell types is interconnected, suggesting that their communication is likely central to the progression of LVV.
In the article, the authors propose that the disruption of key proteins involved in this communication could be a promising strategy for new LVV treatments. The study鈥檚 lead author Dr Robert Maughan said: 鈥淭he most severe damage to tissues is often caused by the body鈥檚 response to persistent inflammation. In LVV, the response of arterial structural cells leads to the affected vessels becoming stiff and narrow. Our work identifies a protein communication network that is likely to be involved in this process and we believe that the targeted manipulation of such networks would be an effective treatment strategy. Of course, further research will be required to develop this concept.鈥�
The team鈥檚 study also evaluated the development of better blood tests for diagnosing and monitoring LVV diseases. Patients with GCA and TAK require regular monitoring to identify relapses i.e. a return of disease activity that can cause further arterial damage. Unfortunately, the currently available blood tests for monitoring disease are inaccurate. Using their proteomic data, the team identified multiple proteins that could be used to monitor disease activity in TAK. Importantly, they showed that these tests could be combined to form 鈥榤ulti-protein signatures鈥� which provide significantly improved diagnostic accuracy compared to current tests.
The first author of the paper, Dr Robert Maughan from the Department of Immunology and Inflammation at Imperial College, noted, 鈥淲ith advances in technology, it is now easier to measure multiple proteins in the blood simultaneously, which is helpful for research and for the development of better blood tests. In this study, we found that multi-protein signatures consistently performed better than single-protein tests. More accurate blood tests have the potential to benefit both patients and hospital services by speeding up diagnosis and by reducing the number of other examinations required.鈥�
The authors emphasised that while this approach has great potential, it is still in its early stages and requires further rigorous testing and development before clinical implementation.
