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 and A. Richard Kitching ()
Additional contact information
Joshua D. Ooi: Monash University Department of Medicine, Monash Medical Centre
Jhih-Hang Jiang: Monash University
Peter J. Eggenhuizen: Monash University Department of Medicine, Monash Medical Centre
Ling L. Chua: Monash University Department of Medicine, Monash Medical Centre
Mirjan van Timmeren: University of Groningen, University Medical Center Groningen
Khai L. Loh: Monash University
Kim M. O’Sullivan: Monash University Department of Medicine, Monash Medical Centre
Poh Y. Gan: Monash University Department of Medicine, Monash Medical Centre
Yong Zhong: Monash University Department of Medicine, Monash Medical Centre
Kirill Tsyganov: Monash University
Lani R. Shochet: Monash University Department of Medicine, Monash Medical Centre
Jessica Ryan: Monash University Department of Medicine, Monash Medical Centre
Coen A. Stegeman: University of Groningen, University Medical Center Groningen
Lars Fugger: University of Oxford
Hugh H. Reid: Monash University
Jamie Rossjohn: Monash University
Peter Heeringa: University of Groningen, University Medical Center Groningen
Stephen R. Holdsworth: Monash University Department of Medicine, Monash Medical Centre
Anton Y. Peleg: Monash University
A. Richard Kitching: Monash University Department of Medicine, Monash Medical Centre

Nature Communications, 2019, vol. 10, issue 1, 1-14

Abstract: Abstract 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.

Date: 2019
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DOI: 10.1038/s41467-019-11255-0

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