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Nat Commun. 2019 Jul 29;10(1):3392. doi: 10.1038/s41467-019-11255-0.

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

Author information

1
Centre for Inflammatory Diseases, Monash University Department of Medicine, Monash Medical Centre, Clayton, VIC, 3168, Australia.
2
Infection and Immunity Program, Monash Biomedicine Discovery Institute and Department of Microbiology, Monash University, Clayton, VIC, 3800, Australia.
3
Department of Paediatrics, Faculty of Medicine, University of Malaya, Kuala Lumpur, 50603, Malaysia.
4
Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, 9700 RB, The Netherlands.
5
Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC, 3800, Australia.
6
Monash Bioinformatics Platform, Monash University, Clayton, VIC, 3800, Australia.
7
Department of Nephrology, Monash Health, Clayton, VIC, 3168, Australia.
8
Department of Internal Medicine, Division of Nephrology, University of Groningen, University Medical Center Groningen, Groningen, 9700 RB, The Netherlands.
9
Oxford Centre for Neuroinflammation, Nuffield Department of Clinical Neurosciences, and MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, OX3 9DS, UK.
10
Australian Research Council Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, VIC, 3800, Australia.
11
Institute of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, CF14-4XN, UK.
12
Department of Infectious Diseases, Alfred Hospital and Central Clinical School, Monash University, Melbourne, VIC, 3004, Australia.
13
Centre for Inflammatory Diseases, Monash University Department of Medicine, Monash Medical Centre, Clayton, VIC, 3168, Australia. richard.kitching@monash.edu.
14
Department of Nephrology, Monash Health, Clayton, VIC, 3168, Australia. richard.kitching@monash.edu.
15
NHMRC Centre for Personalised Immunology, Monash University, Clayton, VIC, 3168, Australia. richard.kitching@monash.edu.
16
Department of Pediatric Nephrology, Monash Health, Clayton, VIC, 3168, Australia. richard.kitching@monash.edu.

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.

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