A plasmid-encoded peptide from Staphylococcus aureus induces anti-myeloperoxidase nephritogenic autoimmunity.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 31358739.
- Also identified by DOI 10.1038/s41467-019-11255-0 and PMC identifier 6662820.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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 (MPO<sub>409-428</sub>), can induce anti-MPO autoimmunity. The peptide (6PGD<sub>391-410</sub>) 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<sub>391-410</sub>, or with S. aureus containing a plasmid expressing 6PGD<sub>391-410</sub>, 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<sub>391-410</sub> is immunogenic in humans, as healthy human and AAV patient sera contain anti-6PGD and anti-6PGD<sub>391-410</sub> antibodies. Therefore, our results support the idea that bacterial plasmids might have a function in autoimmune disease.
Medical subject headings
- Autoimmunity
- Bacterial Proteins
- Heymann Nephritis Antigenic Complex
- Peptides
- Peroxidase
- Staphylococcus aureus