Journal
NATURE COMMUNICATIONS
Volume 10, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-019-11255-0
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Funding
- Australian National Health and Medical Research Council (NHMRC) [1008849]
- NHMRC Center for Research Excellence Grant [1079648]
- NHMRC European Union collaborative research grant as part of the EU Horizon 20/20 RELapses prevention in chronic autoimmune disease (RELENT) Consortium [1115805]
- Wellcome Trust
- Medical Research Council (UK)
- Oak Foundation
- NHMRC Practitioner Fellowship [1117940]
- Australian Research Council Laureate Fellowship
- National Health and Medical Research Council of Australia [1117940, 1115805, 1079648] Funding Source: NHMRC
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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 (6PGD(391-410)) 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 6PGD(391-410), or with S. aureus containing a plasmid expressing 6PGD(391-410), 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 6PGD(391-410) is immunogenic in humans, as healthy human and AAV patient sera contain anti-6PGD and anti-6PGD(391-410) antibodies. Therefore, our results support the idea that bacterial plasmids might have a function in autoimmune disease.
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