Lars Henrik Fugger

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

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

  • Joshua D Ooi, Centre for Inflammatory Diseases, Monash University Department of Medicine, Monash Medical Centre, Clayton, VIC, 3168, Australia.
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  • Jhih-Hang Jiang, Infection and Immunity Program, Monash Biomedicine Discovery Institute and Department of Microbiology, Monash University, Clayton, VIC, 3800, Australia.
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  • Peter J Eggenhuizen, Centre for Inflammatory Diseases, Monash University Department of Medicine, Monash Medical Centre, Clayton, VIC, 3168, Australia.
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  • Ling L Chua, Department of Paediatrics, Faculty of Medicine, University of Malaya, Kuala Lumpur, 50603, Malaysia.
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  • Mirjan van Timmeren, Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, 9700 RB, The Netherlands.
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  • Khai L Loh, Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC, 3800, Australia.
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  • Kim M O'Sullivan, Centre for Inflammatory Diseases, Monash University Department of Medicine, Monash Medical Centre, Clayton, VIC, 3168, Australia.
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  • Poh Y Gan, Centre for Inflammatory Diseases, Monash University Department of Medicine, Monash Medical Centre, Clayton, VIC, 3168, Australia.
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  • Yong Zhong, Centre for Inflammatory Diseases, Monash University Department of Medicine, Monash Medical Centre, Clayton, VIC, 3168, Australia.
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  • Kirill Tsyganov, Monash Bioinformatics Platform, Monash University, Clayton, VIC, 3800, Australia.
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  • Lani R Shochet, Department of Nephrology, Monash Health, Clayton, VIC, 3168, Australia.
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  • Jessica Ryan, Department of Nephrology, Monash Health, Clayton, VIC, 3168, Australia.
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  • Coen A Stegeman, Department of Internal Medicine, Division of Nephrology, University of Groningen, University Medical Center Groningen, Groningen, 9700 RB, The Netherlands.
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  • Lars Fugger
  • Hugh H Reid, Australian Research Council Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, VIC, 3800, Australia.
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  • Jamie Rossjohn, Institute of Infection and Immunity, Cardiff University, School of Medicine, Heath Park, Cardiff CF14 4XN, UK.
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  • Peter Heeringa, Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, 9700 RB, The Netherlands.
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  • Stephen R Holdsworth, Department of Nephrology, Monash Health, Clayton, VIC, 3168, Australia.
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  • Anton Y Peleg, Department of Infectious Diseases, Alfred Hospital and Central Clinical School, Monash University, Melbourne, VIC, 3004, Australia.
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  • A Richard Kitching, Department of Pediatric Nephrology, Monash Health, Clayton, VIC, 3168, Australia. richard.kitching@monash.edu.

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
JournalNature Communications
Volume10
Issue1
Number of pages14
ISSN2041-1723
DOIs
Publication statusPublished - 2019
Externally publishedYes

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