ArticleProceedings of the National Academy of Sciences of the United States of America2012
The immunodominant myeloperoxidase T-cell epitope induces local cell-mediated injury in antimyeloperoxidase glomerulonephritis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 102 citations in OpenAlex.
- Endopeptidase Cleavage of Anti-Glomerular Basement Membrane AntibodiesJournal of the American Society of Nephrology : JASN · 2022Trial
- Current Overview of Multi-omics Analyses in Microscopic Polyangiitis and Granulomatosis with Polyangiitis.Internal medicine (Tokyo, Japan) · 2026Review
- Chimeric autoantibody receptor T cells for targeted depletion of myeloperoxidase-specific anti-neutrophil cytoplasmic antibody-producing B cells.Frontiers in immunology · 2026Article
- CAR-T cells targeting CD19 for the treatment of ANCA vasculitis.Clinical kidney journal · 2025Article
- T-cell immunity in the experimental autoimmune vasculitis rat model.Journal of translational autoimmunity · 2025Article
- Gene therapy enhances deoxyribonuclease I treatment in antimyeloperoxidase glomerulonephritis.JCI insight · 2025Article
- Enigmatic Roles of Complement Anaphylatoxin Signaling in Health and Disease.Immune network · 2025Review
- The evolving landscape of vasculitis management: past, current and emerging.Rheumatology (Oxford, England) · 2025Review
- Regulatory T cell therapy for myeloperoxidase-specific anti-neutrophil cytoplasmic antibody associated vasculitis.Frontiers in immunology · 2025Review
- Immune checkpoint molecules performance in ANCA vasculitis.RMD open · 2024Article
- High-resolution epitope mapping of commercial antibodies to ANCA antigens by yeast surface display.Journal of immunological methods · 2024Article
- CD19-targeting CAR T cells protect from ANCA-induced acute kidney injury.Annals of the rheumatic diseases · 2024Article
- Single-cell multi-omics analysis identifies two distinct phenotypes of newly-onset microscopic polyangiitis.Nature communications · 2023Article
- Animal models for anti-neutrophil cytoplasmic antibody-associated vasculitis: Are current models good enough?Animal models and experimental medicine · 2023Review
- Protective α1-antitrypsin effects in autoimmune vasculitis are compromised by methionine oxidation.The Journal of clinical investigation · 2022Article
- Immune cell behaviour and dynamics in the kidney - insights from in vivo imaging.Nature reviews. Nephrology · 2022Review
- Anaphylatoxins spark the flame in early autoimmunity.Frontiers in immunology · 2022Review
- ANCA-Associated Vasculitis: An Update.Journal of clinical medicine · 2021Review
- Pathogenesis and pathology of anti-neutrophil cytoplasmic antibody（ANCA）-associated vasculitis.Journal of translational autoimmunity · 2021Review
- Emerging Cellular Therapies for Anti-myeloperoxidase Vasculitis and Other Autoimmune Diseases.Frontiers in immunology · 2021Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 3 countries.
Funding
Abstract
Microscopic polyangiitis is an autoimmune small-vessel vasculitis that often manifests as focal and necrotizing glomerulonephritis and renal failure. Antineutrophil cytoplasmic Abs (ANCAs) specific for myeloperoxidase (MPO) play a role in this disease, but the role of autoreactive MPO-specific CD4(+) T cells is uncertain. By screening overlapping peptides of 20 amino acids spanning the MPO molecule, we identified an immunodominant MPO CD4(+) T-cell epitope (MPO(409-428)). Immunizing C57BL/6 mice with MPO(409-428) induced focal necrotizing glomerulonephritis similar to that seen after whole MPO immunization, when MPO was deposited in glomeruli. Transfer of an MPO(409-428)-specific CD4(+) T-cell clone to Rag1(-/-) mice induced focal necrotizing glomerulonephritis when glomerular MPO deposition was induced either by passive transfer of MPO-ANCA and LPS or by planting MPO(409-428) conjugated to a murine antiglomerular basement membrane mAb. MPO(409-428) also induced biologically active anti-MPO Abs in mice. The MPO(409-428) epitope has a minimum immunogenic core region of 11 amino acids, MPO(415-426), with several critical residues. ANCA-activated neutrophils not only induce injury but lodged the autoantigen MPO in glomeruli, allowing autoreactive anti-MPO CD4(+) cells to induce delayed type hypersensitivity-like necrotizing glomerular lesions. These studies identify an immunodominant MPO T-cell epitope and redefine how effector responses can induce injury in MPO-ANCA-associated microscopic polyangiitis.
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Registered trials
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.