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 journalArticleResearchpeer-review

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 languageEnglish
Article number3392
Number of pages14
JournalNature Communications
Volume10
Issue number1
DOIs
Publication statusPublished - 29 Jul 2019

Keywords

  • applied microbiology
  • autoimmune diseases
  • kidney diseases
  • vasculitis syndromes

Cite this

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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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’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}",
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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 journalArticleResearchpeer-review

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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

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