Our work aims to improve outcomes for patients with multi-system autoimmune disorders, particularly vasculitis, lupus and related conditions.
These diseases are often life- or organ-threatening, and historically have been treated with non-specific immunosuppression that, while effective, carried a high burden of side effects.
Our work has led to the widespread introduction of anti-neutrophil cytoplasm antibodies (ANCA) testing in the 1990s, which transformed the understanding and diagnosis of ANCA-associated vasculitis (AAV).
AAV is a group of rare autoimmune diseases affecting small blood vessels. It is driven by ANCA, autoantibodies that target human white blood cells and contribute to small blood vessel damage.
By establishing ANCA as specific markers for systemic vasculitis, these blood tests have enabled faster and more accurate diagnosis, reducing delays and allowing patients to be treated earlier, at a more amenable stage.
We have also repurposed the B-cell depleting drug rituximab for vasculitis and lupus. Our parallel clinical trials in the Europe and the US has led to regulatory approval and global adoption, making rituximab the ‘standard of care’ in AAV. Rituximab induces a higher quality of remission with fewer side effects, and it is more effective in preventing relapse among patients.
In the ADVOCATE study, I led the clinical development of the complement C5a receptor inhibitor avacopan from Phase II through Phase III trials and approval. We’re now examining the real world impact of avacopan in AAV treatment, including kidney function recovery.
We see the development of the clinical service and the development of research activities as very much linked together.
In parallel with drug development and clinical trials, we have worked closely with other translational groups to better understand the science underlying both the cause and the evolution of these diseases, which informs our approach to treatment.
We conducted the first large genomic studies in AAV, confirming the autoimmune basis of the disease and supported B-cell targeting as a fundamental therapeutic strategy.
Following previous EU-funded trials across Europe, I founded the European Vasculitis Society (EUVAS) to bring together researchers across the field of vasculitis. Through close partnership with the NIH-funded Vasculitis Clinical Research Consortium (VCRC), our work has helped deliver a global portfolio of clinical trials that continue to define and refine best practice.
Working at the Cambridge Institute for Therapeutic Immunology and Infectious Disease (CITIID) is a nice example of an academic NHS collaboration, with close links between CITIID academics and the clinical service, and shared principal investigators, fellows and researchers supporting work on both sides.
We're currently working on a true global network to bring together regional and national societies from around the world. And, this is really how you push forward rare disease research by pooling data, pooling samples and pooling expertise.
References
- Smith RM, Jones RB, Specks U, et al. Rituximab versus azathioprine for maintenance of remission for patients with ANCA-associated vasculitis and relapsing disease: an international randomised controlled trial. Annals of the rheumatic diseases. 2023 Jul;82(7):937-44. doi:10.1136/ard-2022-223559
- Jayne DR, Merkel PA, Schall TJ, Bekker P. Avacopan for the treatment of ANCA-associated vasculitis. New England Journal of Medicine. 2021 Feb 18;384(7):599-609. doi: 10.1056/NEJMoa2023386
- Jayne D. Addressing clinical challenges in ANCA-associated vasculitis with real-world evidence. Rheumatology (Oxford). 2026;65(Supplement_1):i20-i26. doi:10.1093/rheumatology/keaf581
- Bashford-Rogers RJM, Bergamaschi L, McKinney EF, et al. Analysis of the B cell receptor repertoire in six immune-mediated diseases. Nature. 2019;574(7776):122-126. doi:10.1038/s41586-019-1595-3
Credits:
Image credit: Karolina Grabowska from Pexels, fernando zhiminaicela from Pixabay, and University of Cambridge