ArticleJournal of the American Society of Nephrology : JASN2008
Antibodies with dual reactivity to plasminogen and complementary PR3 in PR3-ANCA vasculitis.
Article in Journal of the American Society of Nephrology : JASN, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 97 citations in OpenAlex.
- Granulomatosis With Polyangiitis Presenting as Deep Vein Thrombosis in an Adolescent: A Rare Case Report.Clinical case reports · 2026Article
- Childhood-Onset ANCA-Associated Vasculitis: From Genetic Studies to Advances in Pathogenesis, Classification and Novel Therapeutic Approaches.International journal of molecular sciences · 2024Review
- High-resolution epitope mapping of commercial antibodies to ANCA antigens by yeast surface display.Journal of immunological methods · 2024Article
- The intrinsic coagulation pathway plays a dominant role in driving hypercoagulability in ANCA-associated vasculitis.Blood advances · 2024Article
- SARS-CoV-2 and Its Bacterial Co- or Super-Infections Synergize to Trigger COVID-19 Autoimmune Cardiopathies.International journal of molecular sciences · 2023Article
- Autoimmunity: A New Focus on Nasal Polyps.International journal of molecular sciences · 2023Review
- Toll-like Receptor 9 Induced Dendritic Cell Activation Promotes Anti-Myeloperoxidase Autoimmunity and Glomerulonephritis.International journal of molecular sciences · 2023Article
- T Cell Receptor Sequences Amplified during Severe COVID-19 and Multisystem Inflammatory Syndrome in Children Mimic SARS-CoV-2, Its Bacterial Co-Infections and Host Autoantigens.International journal of molecular sciences · 2023Article
- Augmented thrombin formation is related to circulating levels of extracellular vesicles exposing tissue factor and citrullinated histone-3 in anti-neutrophil cytoplasmic antibody-associated vasculitides.Frontiers in medicine · 2023Article
- Caspase-8 activation in neutrophils facilitates autoimmune kidney vasculitis through regulating CD4Frontiers in immunology · 2022Article
- Mechanisms of thrombosis in ANCA-associated vasculitis.Clinical rheumatology · 2021Review
- Diagnostic Dilemma of Paraneoplastic Rheumatic Disorders: Case Series and Narrative Review.Cureus · 2021Article
- ANCA Status or Clinical Phenotype - What Counts More?Current rheumatology reports · 2021Review
- Deep vein thrombosis: An unusual way of revealing microscopic polyangiitis. Deep vein thrombosis in microscopic polyangiitis.Clinical case reports · 2021Article
- ANCA-associated vasculitis.Nature reviews. Disease primers · 2020Review
- Narrative Review of Hypercoagulability in Small-Vessel Vasculitis.Kidney international reports · 2020Review
- Article
- Role of direct oral anticoagulants in patients with kidney disease.Kidney international · 2020Review
- Venous thromboembolism in anti-neutrophil cytoplasmic antibody-associated vasculitis: an underlying prothrombotic condition?Rheumatology advances in practice · 2020Article
- Elevated Microparticle Tissue Factor Activity Differentiates Patients With Venous Thromboembolism in Anti-neutrophil Cytoplasmic Autoantibody Vasculitis.Kidney international reports · 2019Article
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
Patients with inflammatory vascular disease caused by anti-neutrophil cytoplasmic autoantibodies (ANCA) can harbor antibodies not only to the autoantigen proteinase 3 (PR3) but also to complementary PR3 (cPR3(105-201)), a recombinant protein translated from the antisense strand of PR3 cDNA. The purpose of this study was to identify potential endogenous targets of anti-cPR3(105-201) antibodies. Patients' plasmapheresis material was tested for the presence of antigens reactive with affinity-purified rabbit and chicken anti-cPR3(105-201) polyclonal antibodies. Antigen-containing fractions were tested with patients' anti-cPR3(105-201) affinity-purified IgG, and putative protein targets were sequenced by mass spectrometry. Unexpectedly, plasminogen was identified as a target of anti-cPR3(105-201). Reactivity of affinity-purified antibodies from two patients was lost when plasminogen was converted to plasmin, indicating restricted specificity. Antiplasminogen antibodies from five patients bound plasminogen at a surface-exposed loop structure within the protease domain. This loop contains an amino acid motif that is also found in a portion of recombinant cPR3(105-201); site-directed mutagenesis of this sequence decreased antibody reactivity by 30%. Functionally, antiplasminogen antibodies delayed the conversion of plasminogen to plasmin and increased the dissolution time of fibrin clots. Serologically, antiplasminogen antibody levels were higher in PR3-ANCA patients (n = 72) than healthy control subjects (n = 63), myeloperoxidase-ANCA patients (n = 34), and patients with idiopathic thrombosis (n = 57; P = 0.001). Of the patients with PR3-ANCA, nine had documented deep venous thrombosis events, five of whom were positive for antiplasminogen antibodies. In summary, capitalizing on interactions with complementary proteins, specifically complementary PR3, this study identified plasminogen as a previously undescribed autoantigen in PR3-ANCA vasculitis.
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