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

Joshua D Ooi, Jhih-Hang Jiang, Peter J Eggenhuizen, Ling L Chua, Mirjan van Timmeren, Khai L Loh, Kim M O'Sullivan, Poh Y Gan, Yong Zhong, Kirill Tsyganov, Lani R Shochet, Jessica Ryan, Coen A Stegeman, Lars Fugger, Hugh H Reid, Jamie Rossjohn, Peter Heeringa, Stephen R Holdsworth, Anton Y Peleg, A Richard Kitching

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39 Citations (Scopus)
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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.

Original languageEnglish
Article number3392
Number of pages14
JournalNature Communications
Issue number1
Publication statusPublished - 29-Jul-2019


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