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.
| Original language | English |
|---|---|
| Article number | 3392 |
| Number of pages | 14 |
| Journal | Nature Communications |
| Volume | 10 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 29 Jul 2019 |
Keywords
- applied microbiology
- autoimmune diseases
- kidney diseases
- vasculitis syndromes
Cite this
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A plasmid-encoded peptide from Staphylococcus aureus induces anti-myeloperoxidase nephritogenic autoimmunity. / Ooi, Joshua D.; Jiang, Jhih-Hang; Eggenhuizen, Peter J.; Chua, Ling L.; van Timmeren, Mirjan; Loh, Khai L.; O’Sullivan, Kim M.; Gan, Poh Y.; Zhong, Yong; Tsyganov, Kirill; Shochet, Lani R.; Ryan, Jessica; Stegeman, Coen A.; Fugger, Lars; Reid, Hugh H.; Rossjohn, Jamie; Heeringa, Peter; Holdsworth, Stephen R.; Peleg, Anton Y.; Kitching, A. Richard.
In: Nature Communications, Vol. 10, No. 1, 3392, 29.07.2019.Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - A plasmid-encoded peptide from Staphylococcus aureus induces anti-myeloperoxidase nephritogenic autoimmunity
AU - Ooi, Joshua D.
AU - Jiang, Jhih-Hang
AU - Eggenhuizen, Peter J.
AU - Chua, Ling L.
AU - van Timmeren, Mirjan
AU - Loh, Khai L.
AU - O’Sullivan, Kim M.
AU - Gan, Poh Y.
AU - Zhong, Yong
AU - Tsyganov, Kirill
AU - Shochet, Lani R.
AU - Ryan, Jessica
AU - Stegeman, Coen A.
AU - Fugger, Lars
AU - Reid, Hugh H.
AU - Rossjohn, Jamie
AU - Heeringa, Peter
AU - Holdsworth, Stephen R.
AU - Peleg, Anton Y.
AU - Kitching, A. Richard
PY - 2019/7/29
Y1 - 2019/7/29
N2 - 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.
AB - 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.
KW - applied microbiology
KW - autoimmune diseases
KW - kidney diseases
KW - vasculitis syndromes
UR - http://www.scopus.com/inward/record.url?scp=85069908713&partnerID=8YFLogxK
U2 - 10.1038/s41467-019-11255-0
DO - 10.1038/s41467-019-11255-0
M3 - Article
VL - 10
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 3392
ER -