Trial reportJCI insight2021
Circulating autoreactive proteinase 3+ B cells and tolerance checkpoints in ANCA-associated vasculitis.
Trial report in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00104299 (Rituximab Therapy for the Induction of Remission and Tolerance in ANCA-Associated Vasculitis), which is not on this map. Cited by 13 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Rituximab Therapy for the Induction of Remission and Tolerance in ANCA-Associated Vasculitis (ITN021AI)
Who cites it
13 citing papers in PubMed, 18 citations in OpenAlex.
- Next-generation immune cell engagers for B cell depletion in autoimmune diseases.Nature reviews. Drug discovery · 2026Review
- Immature leukocyte and plasma-induced cell death reveal subclinical immune activation in EGPA patients in remission.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- Differentiating naturally occurring and disease associated autoantibodies in MPO-ANCA vasculitis through immunogenomic and epitope comparisons.Frontiers in medicine · 2026Article
- BAFF and APRIL signaling in the B-cell lineage: implications for the pathogenesis of ANCA-associated vasculitis.Frontiers in immunology · 2026Review
- B cell receptor signaling in autoimmune rheumatic diseases: regulatory mechanisms and therapeutic targeting.Frontiers in immunology · 2026Review
- Aging in Granulomatosis with Polyangiitis and Microscopic Polyangiitis: From Pathophysiology to Clinical Management.Drugs & aging · 2025Review
- Review
- Anti-myeloperoxidase IgM B cells in anti-neutrophil cytoplasmic antibody-associated vasculitis.Nature communications · 2025Article
- Circulating B cells display differential immune regulatory molecule expression in granulomatosis with polyangiitis.Clinical and experimental immunology · 2025Article
- Rituximab in PR3-ANCA positive patients with moderately to severely active ulcerative colitis: a multicenter real-world pilot study.Frontiers in pharmacology · 2025Article
- Autoreactive Plasmablasts After B Cell Depletion With Rituximab and Relapses in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.Arthritis & rheumatology (Hoboken, N.J.) · 2023Article
- A glance into the future of anti-neutrophil cytoplasmic antibody-associated vasculitis.Therapeutic advances in musculoskeletal disease · 2022Review
- Polygenic autoimmune disease risk alleles impacting B cell tolerance act in concert across shared molecular networks in mouse and in humans.Frontiers in immunology · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
26 authors at 12 institutions in 4 countries.
Funding
Abstract
BACKGROUNDLittle is known about the autoreactive B cells in antineutrophil cytoplasmic antibody-associated (ANCA-associated) vasculitis (AAV). We aimed to investigate tolerance checkpoints of circulating antigen-specific proteinase 3-reactive (PR3+) B cells.METHODSMulticolor flow cytometry in combination with bioinformatics and functional in vitro studies were performed on baseline samples of PBMCs from 154 well-characterized participants of the RAVE trial (NCT00104299) with severely active PR3-AAV and myeloperoxidase-AAV (MPO-AAV) and 27 healthy controls (HCs). Clinical data and outcomes from the trial were correlated with PR3+ B cells (total and subsets).RESULTSThe frequency of PR3+ B cells among circulating B cells was higher in participants with PR3-AAV (4.77% median [IQR, 3.98%-6.01%]) than in participants with MPO-AAV (3.16% median [IQR, 2.51%-5.22%]) and participants with AAV compared with HCs (1.67% median [IQR, 1.27%-2.16%], P < 0.001 for all comparisons), implying a defective central tolerance checkpoint in patients with AAV. Only PBMCs from participants with PR3-AAV contained PR3+ B cells capable of secreting PR3-ANCA IgG in vitro, proving they were functionally distinct from those of participants with MPO-AAV and HCs. Unsupervised clustering identified subtle subsets of atypical autoreactive PR3+ memory B cells accumulating through the maturation process in patients with PR3-AAV. PR3+ B cells were enriched in the memory B cell compartment of participants with PR3-AAV and were associated with higher serum CXCL13 levels, suggesting an increased germinal center activity. PR3+ B cells correlated with systemic inflammation (C-reactive protein and erythrocyte sedimentation rate, P < 0.05) and complete remission (P < 0.001).CONCLUSIONThis study suggests the presence of defective central antigen-independent and peripheral antigen-dependent checkpoints in patients with PR3-AAV, elucidating the selection process of autoreactive B cells.Trial registrationClinicalTrials.gov NCT00104299.FundingThe Vasculitis Foundation, the National Institute of Allergy and Infectious Diseases of the NIH, and the Mayo Foundation for Education and Research.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.