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Ooi, Joshua D; Jiang, Jhih-Hang; Eggenhuizen, Peter J; Chua, Ling L; van Timmeren, Mirjan; Loh, Khai L; O'Sullivan, Kim M; Gan, Poh Y; Zhong, Yong; Tsyganov, Kirill; Shochet, Lani R; Ryan, Jessica; Stegeman, Coen A; Fugger, Lars; Reid, Hugh H; Rossjohn, Jamie; Heeringa, Peter; Holdsworth, Stephen R; Peleg, Anton Y; Kitching, A Richard
Nature communications, 07/2019, Volume: 10, Issue: 1Journal Article
Autoreactivity to myeloperoxidase (MPO) causes anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), with rapidly progressive glomerulonephritis. Here, we show that a Staphylococcus aureus peptide, homologous to an immunodominant MPO T-cell epitope (MPO ), can induce anti-MPO autoimmunity. The peptide (6PGD ) is part of a plasmid-encoded 6-phosphogluconate dehydrogenase found in some S. aureus strains. It induces anti-MPO T-cell autoimmunity and MPO-ANCA in mice, whereas related sequences do not. Mice immunized with 6PGD , or with S. aureus containing a plasmid expressing 6PGD , develop glomerulonephritis when MPO is deposited in glomeruli. The peptide induces anti-MPO autoreactivity in the context of three MHC class II allomorphs. Furthermore, we show that 6PGD is immunogenic in humans, as healthy human and AAV patient sera contain anti-6PGD and anti-6PGD antibodies. Therefore, our results support the idea that bacterial plasmids might have a function in autoimmune disease.
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