ArticleProceedings of the National Academy of Sciences of the United States of America2011
IgA and IgG antineutrophil cytoplasmic antibody engagement of Fc receptor genetic variants influences granulomatosis with polyangiitis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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47 citing papers in PubMed, 84 citations in OpenAlex.
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- Circulating B cells display differential immune regulatory molecule expression in granulomatosis with polyangiitis.Clinical and experimental immunology · 2025Article
- A genetically determined molecular switch modulates the anti-inflammatory potential of human IgA.Frontiers in immunology · 2025Article
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- Predictors of poor prognosis in ANCA-associated vasculitis (AAV): a single-center prospective study of inpatients in China.Clinical and experimental medicine · 2023Article
- Neutrophil extracellular trap formation in anti-neutrophil cytoplasmic antibody-associated and large-vessel vasculitis.Clinical immunology (Orlando, Fla.) · 2023Article
- Pathogenesis of anti-neutrophil cytoplasmic antibody-associated vasculitis.Rheumatology and immunology research · 2023Review
- Unmet needs in ANCA-associated vasculitis: Physicians' and patients' perspectives.Frontiers in immunology · 2023Review
- Specific IgG glycosylation differences precede relapse in PR3-ANCA associated vasculitis patients with and without ANCA rise.Frontiers in immunology · 2023Article
- Epidemiology and genetics of granulomatosis with polyangiitis.Rheumatology international · 2021Review
- Type I interferon response and vascular alteration in chilblain-like lesions during the COVID-19 outbreak.The British journal of dermatology · 2021Observational
- IgA vasculitis.Seminars in immunopathology · 2021Review
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- The gut microbiome in microscopic polyangiitis with kidney involvement: common and unique alterations, clinical association and values for disease diagnosis and outcome prediction.Annals of translational medicine · 2021Article
- IgA nephropathy with serum ANCA positivity: case series and literature review.Rheumatology international · 2021Review
- Endothelial cells response to neutrophil-derived extracellular vesicles miRNAs in anti-PR3 positive vasculitis.Clinical and experimental immunology · 2021Observational
- Advances in the genomics of ANCA-associated vasculitis-a view from East Asia.Genes and immunity · 2021Review
- Pathogenicity of Proteinase 3-Anti-Neutrophil Cytoplasmic Antibody in Granulomatosis With Polyangiitis: Implications as Biomarker and Future Therapies.Frontiers in immunology · 2021Review
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25 authors at 15 institutions in 4 countries.
Funding
Abstract
Granulomatosis with polyangiitis (Wegener's) is a rare autoimmune neutrophil-mediated vasculitis that can cause renal disease and mucosal manifestations. Antineutrophil cytoplasmic antibodies (ANCA) are present in many patients, vary in level over time, and induce neutrophil activation through engagement with Fc receptors (FcRs). Given roles for FcRs in ANCA-mediated neutrophil activation and IgA antibodies in mucosal immunity, we hypothesized that FcR genetics and previously unappreciated IgA ANCA affect clinical presentation. We assembled a total of 673 patients and 413 controls from two multicenter cohorts, performed ELISA and immunofluorescence assays to determine IgA and IgG ANCA positivity, and used Illumina, TaqMan, or Pyrosequencing to genotype eight haplotype-tagging SNPs in the IgA FcR (FCAR) and to determine NA1/NA2 genotype of FCGR3B, the most prevalent neutrophil IgG FcR. We evaluated neutrophil activation by measuring degranulation marker CD11b with flow cytometry or neutrophil extracellcular trap formation with confocal microscopy. Functional polymorphisms in FCGR3B and FCAR differed between patient groups stratified by renal involvement. IgA ANCA were found in ∼30% of patients and were less common in patients with severe renal disease. Neutrophil stimulation by IgA or IgG ANCA led to degranulation and neutrophil extracellcular trap formation in a FcR allele-specific manner (IgA:FCAR P = 0.008; IgG:FCGR3B P = 0.003). When stimulated with IgA and IgG ANCA together, IgG ANCA induced neutrophil activation was reduced (P = 0.0001). FcR genotypes, IgA ANCA, and IgG ANCA are potential prognostic and therapeutic targets for understanding the pathogenesis and presentation of granulomatosis with polyangiitis (Wegener's).
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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.