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

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.

• Authors: 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, A Richard Kitching
• Journal: Nature communications (Nat Commun) Vol. 10 Issue 1 Pg. 3392 (07 29 2019) ISSN: 2041-1723 [Electronic] England
• PMID: 31358739 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Bacterial Proteins
• Epitopes, T-Lymphocyte
• Heymann Nephritis Antigenic Complex
• Peptides
• Peroxidase

Topics

• Amino Acid Sequence
• Animals
• Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis (blood, immunology)
• Autoimmunity (immunology)
• Bacterial Proteins (genetics, immunology)
• Epitopes, T-Lymphocyte (genetics, immunology)
• Glomerulonephritis (immunology)
• Heymann Nephritis Antigenic Complex (immunology, metabolism)
• Humans
• Male
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Mice, Knockout
• Mice, Transgenic
• Peptides (genetics, immunology)
• Peroxidase (immunology, metabolism)
• Plasmids (genetics)
• Staphylococcus aureus (genetics, immunology, physiology)