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

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

doi:10.1038/s41467-019-11255-0

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

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

Research output: Contribution to journal › Article › Research › peer-review

16 Citations (Scopus)

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_409–428), 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.

Original language	English
Article number	3392
Number of pages	14
Journal	Nature Communications
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41467-019-11255-0
Publication status	Published - 29 Jul 2019

Keywords

applied microbiology
autoimmune diseases
kidney diseases
vasculitis syndromes

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10.1038/s41467-019-11255-0

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NOVEL SOLUTIONS FOR ANTIMICROBIAL RESISTANT PATHOGENS
Peleg, A.
1/01/17 → 31/12/21
Project: Research
RELapses prevENTion in chronic autoimmune disease: common mechanisms and co-morbidities (RELENT)
Kitching, R.
National Health and Medical Research Council (NHMRC) (Australia)
1/01/16 → 31/12/19
Project: Research
Center for Personalised Immunology
Vinuesa, C. G., Cook, M. C., Fulcher, D. A., Alexander, S., Kitching, R., Enders, A., Casellas, R., Field, M. A., Schwarz, K. & Andrews, T. D.
National Health and Medical Research Council (NHMRC) (Australia)
1/12/14 → 30/11/19
Project: Research

Cite this

Ooi, J. D., Jiang, J-H., Eggenhuizen, P. J., Chua, L. L., van Timmeren, M., Loh, K. L., O’Sullivan, K. M., Gan, P. Y., Zhong, Y., Tsyganov, K., Shochet, L. R., Ryan, J., Stegeman, C. A., Fugger, L., Reid, H. H., Rossjohn, J., Heeringa, P., Holdsworth, S. R., Peleg, A. Y., & Kitching, A. R. (2019). A plasmid-encoded peptide from Staphylococcus aureus induces anti-myeloperoxidase nephritogenic autoimmunity. Nature Communications, 10(1), [3392]. https://doi.org/10.1038/s41467-019-11255-0

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. / A plasmid-encoded peptide from Staphylococcus aureus induces anti-myeloperoxidase nephritogenic autoimmunity. In: Nature Communications. 2019 ; Vol. 10, No. 1.

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title = "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.",

keywords = "applied microbiology, autoimmune diseases, kidney diseases, vasculitis syndromes",

author = "Ooi, {Joshua D.} and Jhih-Hang Jiang and Eggenhuizen, {Peter J.} and Chua, {Ling L.} and {van Timmeren}, Mirjan and Loh, {Khai L.} and O{\textquoteright}Sullivan, {Kim M.} and Gan, {Poh Y.} and Yong Zhong and Kirill Tsyganov and Shochet, {Lani R.} and Jessica Ryan and Stegeman, {Coen A.} and Lars Fugger and Reid, {Hugh H.} and Jamie Rossjohn and Peter Heeringa and Holdsworth, {Stephen R.} and Peleg, {Anton Y.} and Kitching, {A. Richard}",

year = "2019",

month = jul,

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doi = "10.1038/s41467-019-11255-0",

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Ooi, JD , Jiang, J-H, Eggenhuizen, PJ, Chua, LL, van Timmeren, M, Loh, KL, O’Sullivan, KM , Gan, PY, Zhong, Y, Tsyganov, K, Shochet, LR, Ryan, J, Stegeman, CA, Fugger, L, Reid, HH , Rossjohn, J, Heeringa, P, Holdsworth, SR , Peleg, AY & Kitching, AR 2019, 'A plasmid-encoded peptide from Staphylococcus aureus induces anti-myeloperoxidase nephritogenic autoimmunity', Nature Communications, vol. 10, no. 1, 3392. https://doi.org/10.1038/s41467-019-11255-0

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

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AU - Tsyganov, Kirill

AU - Shochet, Lani R.

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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.

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

Abstract

Keywords

Access to Document

Projects

NOVEL SOLUTIONS FOR ANTIMICROBIAL RESISTANT PATHOGENS

RELapses prevENTion in chronic autoimmune disease: common mechanisms and co-morbidities (RELENT)

Center for Personalised Immunology

Cite this