Poster presenter: Dorian Grépilloux, MD, Nephrology Resident, Grenoble University Hospital, France
Poster title: Mapping Complement Activation Profiles in ANCA-Associated Vasculitides
Poster Session B: 10:30 a.m.–12:30 p.m., Monday, November 9
What is your poster about?
Dr. Grépilloux: My poster describes a cross-sectional study of 96 patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and 48 healthy controls. I conducted this research at Cochin Hospital in Paris, under the supervision of Prof. Benjamin Terrier and the French Vasculitis Study Group. We compared 15 complement analytes spanning the classical, alternative, central, and terminal pathways, together with main regulators, and described three complement activation profiles: terminal activation (elevated sC5b-9, 25% of patients), proximal/central activation without distal activation (elevated Bb and/or C3a, 48%), and low activation (27%).
We show that AAV patients displayed a selective alternative-pathway signature compared with controls, independent of kidney function and that, among AAV patients, low activation predominated in PR3-ANCA-positive granulomatosis with polyangiitis (GPA) compared to myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA)-positive microscopic polyangiitis (MPA). Increasing complement activation was associated with higher C-reactive protein (CRP) levels, higher neutrophil-to-lymphocyte ratio (NLR), and higher levels of acute phase proteins on NULISA profiling, and correlated with lower glomerular chronicity and a trend toward more cellular crescents on kidney biopsy.
Why did you decide to investigate this topic?
Dr. Grépilloux: The pathophysiology of AAV involves the complement system, particularly through overactivation of the alternative pathway, leading notably to the production of C5a, which plays a pivotal role in neutrophil priming. The ADVOCATE trial testing avacopan had raised high hopes regarding the potential of complement-inhibiting therapies in AAV prior to its retraction in June 2026. However, several clinical trials are still ongoing, evaluating various inhibitors such as iptacopan and tarperprumig in AAV. Despite this, the complement activation profiles within a large cohort of patients with AAV remained unknown. We therefore decided to conduct this study to better characterize each patient’s profile, with the aim of better guiding personalized treatment with complement inhibitors in the future.
What are you working on next related to this research?
Dr. Grépilloux: Our research will now focus on extending our work to urinary complement analytes and on identifying reliable and reproducible biomarkers to use in clinical practice, in order to identify patients whose disease is heavily driven by complement activation and who are likely to benefit the most from complement-inhibiting therapies.
What excites you most about your work?
Dr. Grépilloux: Our study provides insights into the complement activation profile within a cohort of 96 patients with vasculitis, highlighting distinct profiles among individual patients. Based on these results, it is apparent that patient stratification will probably be necessary when introducing complement inhibitor therapy, as some patients may benefit more from these treatments than others. Our study strongly supports the use of personalized medicine in the management of AAV. That is especially true at a time when anti-complement therapies are starting to emerge.
What are you most looking forward to at ACR Convergence 2026 in Orlando?
Dr. Grépilloux: I’m really looking forward to the chance to exchange with clinicians and researchers from around the world on this topic, and to discuss their perspective on our findings. I’m also really excited about attending the high-quality talks covering the latest advances in rheumatology.
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