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• W2142785209 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 (<i>cPR3</i>^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-<i>cPR3</i>^105–201 antibodies. Patients’ plasmapheresis material was tested for the presence of antigens reactive with affinity-purified rabbit and chicken anti-<i>cPR3</i>^105–201 polyclonal antibodies. Antigen-containing fractions were tested with patients’ anti-<i>cPR3</i>^105–201 affinity-purified IgG, and putative protein targets were sequenced by mass spectrometry. Unexpectedly, plasminogen was identified as a target of anti-<i>cPR3</i>^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 <i>cPR3</i>^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 (<i>n</i> = 72) than healthy control subjects (<i>n</i> = 63), myeloperoxidase-ANCA patients (<i>n</i> = 34), and patients with idiopathic thrombosis (<i>n</i> = 57; <i>P</i> = 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." @default.
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• W2142785209 date "2008-12-01" @default.
• W2142785209 modified "2023-10-18" @default.
• W2142785209 title "Antibodies with Dual Reactivity to Plasminogen and Complementary PR3 in PR3-ANCA Vasculitis" @default.
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• W2142785209 doi "https://doi.org/10.1681/asn.2008030270" @default.
• W2142785209 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2588098" @default.
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