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

Ooi JD 1 , Jiang JH 2 , Eggenhuizen PJ 1 , Chua LL 1 , van Timmeren M 3 , Loh KL 4 Show all authors , O'Sullivan KM 1 , Gan PY 1 , Zhong Y 1 , Tsyganov K 5 , Shochet LR 1 , Ryan J 1 , Stegeman CA 6 , Fugger L 7 , Reid HH 4 , Rossjohn J 4 , Heeringa P 3 , Holdsworth SR 1 , Peleg AY 2 , Kitching AR 8

Affiliations 

  • 1 Centre for Inflammatory Diseases, Monash University Department of Medicine, Monash Medical Centre, Clayton, VIC, 3168, Australia
  • 2 Infection and Immunity Program, Monash Biomedicine Discovery Institute and Department of Microbiology, Monash University, Clayton, VIC, 3800, Australia
  • 3 Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, 9700 RB, The Netherlands
  • 4 Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC, 3800, Australia
  • 5 Monash Bioinformatics Platform, Monash University, Clayton, VIC, 3800, Australia
  • 6 Department of Internal Medicine, Division of Nephrology, University of Groningen, University Medical Center Groningen, Groningen, 9700 RB, The Netherlands
  • 7 Oxford Centre for Neuroinflammation, Nuffield Department of Clinical Neurosciences, and MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, OX3 9DS, UK
  • 8 Centre for Inflammatory Diseases, Monash University Department of Medicine, Monash Medical Centre, Clayton, VIC, 3168, Australia. richard.kitching@monash.edu
Nat Commun, 2019 07 29;10(1):3392.
PMID: 31358739 DOI: 10.1038/s41467-019-11255-0

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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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