News and Resources
News
February 2025
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 following blood vessel narrowing or damage, such as sight loss, stroke, or aortic aneurysms. 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 for the design of trials testing the effectiveness of new treatments.
Last month, NIHR BRC funded investigators from Imperial, University of Leeds and the University of Oxford published new research in Arthritis and Rheumatology addressing these questions in the most extensive study of its kind. The team used new ‘proteomic’ 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. Proteins play a critical role in most biological functions, and proteomics can provide a powerful snapshot or profile of a person’s or group's biological state. The team found that the protein profiles in GCA and TAK arteritis were surprisingly similar, indicating significant overlap in the biology of these diseases. Notably, the shared profiles emphasised the important roles of macrophages—key immune cells—and structural cells of the artery in LVV. 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’s lead author Dr Robert Maughan said: “The most severe damage to tissues is often caused by the body’s 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.”
The team’s study may also help in 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 diagnosing and monitoring disease are inaccurate. Using their proteomic data, the team identified multiple proteins that could be used to monitor disease activity in in TAK. Importantly, they showed that these tests could be combined to form ‘multi-protein signatures’ which provide significantly improved diagnostic accuracy compared to current tests. Dr Maughan noted: “With 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 to monitor disease activity.” 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.
This study was initiated through an MRC TARGET Partnership award leading to an ongoing collaboration between the Imperial, Leeds and Oxford NIHR Biomedical Research Centres with additional funding from NIHR, Vasculitis UK, the Medical Research Foundation and UKRI.
February 2023
Rare Disease Day, 28 February 2023: 3.5 million people in the UK are affected by a rare condition - that's 1 in 17 people
Many rare conditions are lifelong and complex. As a result, people affected by rare conditions often need support and expertise from a wide range of healthcare professionals such as GPs, specialist hospital consultants, specialist nurses, physiotherapists, occupational therapists, speech and language therapists, and learning disability nurses. This can mean having multiple appointments across different settings and on different dates.
The Leeds Teaching Hospitals NHS Trust hosts one of the 18 national NIHR BioResource Centres, which is led by centre Director, Dr Sinisa Savic. The NIHR Leeds BioResource centre is committed to delivering research to transform the outcomes and lives of people with a range of rare and common diseases.
Dr Sinisa Savic said: "In Leeds, research is underway with patients who are involved in studies including rare diseases such as primary immunodeficiencies (PID), autoimmune vasculitis, giant cell arteritis (GCA) and cystic fibrosis, and more common conditions including inflammatory bowel disease and the immune-mediated inflammatory diseases.
"Through previous and current studies in Leeds, we have contributed to significant breakthroughs in the understanding of genetic causes of rare diseases such as PID and GCA. The advances in PID have directly led to improved patient outcomes, since we are able to offer targeted, individualised treatment options. This understanding is helping people with rare conditions to live longer, better quality lives, and has been key to national and international research taking place in this complex area."
Professor Ann Morgan, Professor of Rheumatology at the University of Leeds is taking forward a research project into vasculitis, including GCA, which are a group of rare diseases where repeated attacks of inflammation occur in the walls of blood vessels.
Professor Morgan said: "The project that I am leading aims to understand what causes different types of vasculitis. This is an important area of research as vasculitis can affect men, women and children of all ages. A key clinical challenge in caring for people with vasculitis is to balance how well the immune system is controlled to prevent complications, against over-suppression of the immune system which can lead to infections.
Analysing the data generated by this project will help us to understand more about the parts of the immune system altered in vasculitis and how these change with treatment. This improved understanding will help us find new treatments for vasculitis or allow us to use existing treatments in a different type of vasculitis."
People who are living with and without health conditions can volunteer for BioResource studies taking place at Leeds Teaching Hospitals NHS Trust. For more information, the team can be contacted on 0113 206 0476 or by email at leedsth-tr.nihrbioresource@nhs.net
Find out more online.
December 2019
The British Society for Rheumatology guideline on diagnosis and treatment of giant cell arteritis.
Guidance for clinicians in the diagnosis and treatment of GCA, supported by evidence where possible.
The BSR clinical practice guidelines on giant cell arteritis: five years in the making by Sarah Mackie and Peter Lanyon (Executive Summary and full version).
January 2019
Wellcome Trust Fellowship for Gary Reynolds
Gary Reynolds (Clinical Lecturer at Newcastle University and Specialty Trainee in Rheumatology at the Freeman Hospital) has been awarded a Wellcome Trust Clinical Research Career Development Fellowship for his project examining the role of multinucleated giant cells (MGCs) in GCA. MGCs develop in a range of inflammatory conditions but their functional role is unclear. In this proposal, he intends to apply single cell genomic techniques to understand the transcriptional landscape of GCA-affected temporal artery tissue and use this to validate an in vitro model of MGCs. The aim is to use this model to trial novel therapeutics to target macrophage dysfunction in GCA. The fellowship will last four years starting in mid-2019.
July 2018
Commissioning of Tocilizumab for Giant cell Arteritis in the NHS
The TARGET Partnership are proposing to establish a UK post-marketing surveillance registry to study the effectiveness, safety and prescribing habits of Tocilizumab for the treatment of giant cell arteritis in the UK National Health Service, nested within the existing structure of the UK GCA Consortium and UKIVAS studies. For more information, please get in touch (c.j.harden@leeds.ac.uk).
March 2018
- The University of Leeds is hosting a Roche-sponsored Breakfast Meeting to link with the launch of Roche’s launch of GCA research.
- Professor John Stone, Professor Ann Morgan, Dr Sarah Mackie and Dr Mar Pujades-Rodriguez will all provide talks on the themes of GCA research and steroid toxicity
Our Recent Publications
2025
Weber A, Zulcinski M, Haroon-Rashid L, Kuszlewicz B, Driessen A, Newton D, Morgan AW, Martínez MR. (2025). Identification of clonally expanded T-cell receptor sequences in giant cell arteritis. J Autoimmun.
Maughan R, MacDonald-Dunlop E, Haroon-Rashid L, Sorensen L, Chaddock N, Masters S, Porter A, Peverelli M, Pericleous C, Hutchings A, Robinson J, Youngstein T, Luqmani R, Mason J, Morgan AW, Peters J. (2025). Proteomic profiling of the large vessel vasculitis spectrum identifies shared signatures of innate immune activation and stromal remodelling. A&R.
2024
Chaddock NJM, Harden CJ, Sorensen L, Mathieson HR, Zulcinski M, Lawson K, O'Sullivan E, Mollan S, Martin J, Mackie SL, Iles MM, Morgan AW on behalf of the UKGCA Consortium. (2024). Age, anti-coagulants, hypertension and cardiovascular genetic traits predict cranial ischaemic complications in patients with giant cell arteritis. Ann Rheum Dis.
Chatzigeoriou C, Barrett JH, Martin J, Morgan AW, Mackie SL, UK GCA Consortium. (2024). Estimating overdiagnosis in giant cell arteritis diagnostic pathways using genetic data: genetic association study. Rheumatology (Oxford).
Manning JE, Harris E, Mathieson H, Sorensen L, Luqmani R, McGettrick HM, Morgan AW, Young SP, Mackie SL. (2024). Polymyalgia rheumatica shows metabolomic alterations that are further altered by glucocorticoid treatment: identification of metabolic correlates of fatigue. J Autoimmun.
Borrego-Yaniz G, Ortiz-Fernández L, Madrid-Paredes A, Kerick M, Hernández-Rodríguez J, Mackie SL, Vaglio A, Castañeda S, Solans R, Mestre-Torres J, Khalidi N, Langford CA, Ytterberg S, Beretta L, Govoni M, Emmi G, Cimmino MA, Witte T, Neumann T, Holle J, Schönau V, Pugnet G, Papo T, Haroche J, Mahr A, Mouthon L, Molberg Ø, Diamantopoulos AP, Voskuyl A, Daikeler T, Berger CT, Molloy ES, Blockmans D, van Sleen Y, Iles M, Sorensen L, Luqmani R, Reynolds G, Bukhari M, Bhagat S, Spanish GCA Group, UK GCA Consortium, Vasculitis Clinical Research Consortium, Ortego-Centeno N, Brouwer E, Lamprecht P, Klapa S, Salvarani C, Merkel PA, Cid MC, González-Gay MA, Morgan AW, Martin J, Marquez A. (2024) Risk loci involved in giant cell arteritis susceptibility: a genome-wide association study. Lancet Rheumatol.
van Praagh GD, Nienhuis PH, Reijrink M, Davidse M, Duff LM, Spottiswoode BS, Mulder DJ, Prakken NHJ, Scarsbrook AF, Morgan AW, Tsoumpas C, Wolterink JM, Mouridsen KB, Borra RJH, Sinha B, Slart RHJA. (2024). Automated multiclass segmentation, quantification, and visualization of the diseased aorta on hybrid PET/CT – SEQUIA. J Med Phys.
Taze D, Chakrabarty A, Venkateswaran R, Hartley C, Harden C, Morgan AW, Mackie SL, Griffin KJ. (2024). Histopathology reporting of temporal artery biopsy specimens for giant cell arteritis: results of a modified Delphi study. J Clin Pathol.
2023
Chatzigeorgiou C, Taylor JC, Elliott F, O'Sullivan EP, Morgan AW, Barrett JH, Mackie SL, on behalf of UK Biobank Eye and Vision Consortium. (2023). Common co-morbidities in polymyalgia rheumatica and giant cell arteritis: cross-sectional study in UK Biobank. Rheumap.
Duff LM, Scarsbrook AF, Ravikumar N, Frood R, van Praagh GD, Mackie SL, Bailey MA, Tarkin JM, Mason JC, van der Geest KSM, Slart RHJA, Morgan AW, Tsoumpas C. (2023). An automated method for artificial intelligence assisted diagnosis of active aortitis using radiomic analysis of FDG PET-CT images. Biomolecules.
2022
Duff L, Scarsbrook A, Mackie S, Frood R, Bailey M, Morgan AW, Tsoumpas C. (2022). A methodological framework for AI-assisted diagnosis of active aortitis using radiomic analysis of FDG PET-CT images: Initial analysis. J Nucl Cardiol.
Poulter J, UKGCA/Vexas Consortium, Morgan AW, Cargo C, Savic S. (2022). A high-throughput amplicon screen for somatic UBA1 variants in Cytopenic and Giant Cell Arteritis cohorts. J Clin Immunol.
2020
Pujades-Rodriguez M, Morgan AW, Cubbon RM, Wu J. (2020). Dose-dependent oral glucocorticoid cardiovascular risks in people with immune-mediated inflammatory diseases: a population-based cohort study. PLoS Med.
Baxter EW, Graham AE, Re NA, Carr IM, Robinson JI, Mackie SL, Morgan AW. (2020). Standardized protocols for differentiation of THP-1 cells to macrophages with distinct M (IFNy+LPS), M(IL-4) and M(IL-10) phenotypes. J Immunol Methods.
2019
Svasti-Salee CR, Mollan SP, Morgan AW, Quick V. (2019). Rapid visual recovery following intravenous tocilizumab in glucocorticoid resistant refractory giant cell arteritis. BMJ Case Reports.
Mebrahtu TF, Morgan AW, Keeley A, Baxter PD, Stewart PM, Pujades-Rodriguez M. (2019). Dose dependency of iatrogenic glucocorticoid excess and adrenal insufficiency and mortality: a cohort study in England. J Clin Endocrinol Metab.
Wu J, Keeley A, Mallen C, Morgan AW, Pujades-Rodriguez M. (2019). Incidence of infections associated with oral glucocorticoid dose in people diagnosed with polymyalgia rheumatica or giant cell arteritis: a cohort study in England. CMAJ.
Flurey CA, Tugwell PS, Black RJ, Halls S, Page MJ, Robson JC, … Richards B. (2019). The OMERACT Emerging Leaders Program: The Good, the Bad and the Future. J Rheumatol.
Robson JC, Jayne D, Merkel PA, Dawson J. (2019). Systemic vasculitis and patient-reported outcomes: how the assessment of patient preferences and perspectives could improve outcomes. Patient Related Outcome Measures.