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A plasmid-encoded peptide from Staphylococcus aureus induces anti-myeloperoxidase nephritogenic autoimmunity

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. and Kitching, A. Richard 2019. A plasmid-encoded peptide from Staphylococcus aureus induces anti-myeloperoxidase nephritogenic autoimmunity. Nature Communications 10 (1) , 3392. 10.1038/s41467-019-11255-0

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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 (MPO409–428), can induce anti-MPO autoimmunity. The peptide (6PGD391–410) 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 6PGD391–410, or with S. aureus containing a plasmid expressing 6PGD391–410, 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 6PGD391–410 is immunogenic in humans, as healthy human and AAV patient sera contain anti-6PGD and anti-6PGD391–410 antibodies. Therefore, our results support the idea that bacterial plasmids might have a function in autoimmune disease.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Publisher: Nature Research
ISSN: 2041-1723
Date of First Compliant Deposit: 19 August 2019
Date of Acceptance: 26 June 2019
Last Modified: 14 Nov 2019 14:10

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