A plasmid-encoded peptide from Staphylococcus aureus induces anti-myeloperoxidase nephritogenic autoimmunity
<p>Autoreactivity to myeloperoxidase (MPO) causes anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), with rapidly progressive glomerulonephritis. Here, we show that a <em>Staphylococcus aureus</em> peptide, homologous to an immunodominant MPO...
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
Nature Research
2019
|
| _version_ | 1797103481112231936 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Ooi, JD |
| collection | OXFORD |
| description | <p>Autoreactivity to myeloperoxidase (MPO) causes anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), with rapidly progressive glomerulonephritis. Here, we show that a <em>Staphylococcus aureus</em> peptide, homologous to an immunodominant MPO T-cell epitope (MPO<sub>409–428</sub>), can induce anti-MPO autoimmunity. The peptide (6PGD<sub>391–410</sub>) is part of a plasmid-encoded 6-phosphogluconate dehydrogenase found in some <em>S. aureus</em> strains. It induces anti-MPO T-cell autoimmunity and MPO-ANCA in mice, whereas related sequences do not. Mice immunized with 6PGD<sub>391–410</sub>, or with <em>S. aureus</em> containing a plasmid expressing 6PGD<sub>391–410</sub>, 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<sub>391–410</sub> is immunogenic in humans, as healthy human and AAV patient sera contain anti-6PGD and anti-6PGD<sub>391–410</sub> antibodies. Therefore, our results support the idea that bacterial plasmids might have a function in autoimmune disease.</p> |
| first_indexed | 2024-03-07T06:20:44Z |
| format | Journal article |
| id | oxford-uuid:f2a21596-a878-4564-a6a8-8b008934ea13 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T06:20:44Z |
| publishDate | 2019 |
| publisher | Nature Research |
| record_format | dspace |
| spelling | oxford-uuid:f2a21596-a878-4564-a6a8-8b008934ea132022-03-27T12:05:27ZA plasmid-encoded peptide from Staphylococcus aureus induces anti-myeloperoxidase nephritogenic autoimmunityJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:f2a21596-a878-4564-a6a8-8b008934ea13EnglishSymplectic ElementsNature Research2019Ooi, JDJiang, J-HEggenhuizen, PJChua, LLvan Timmeren, MLoh, KLO'Sullivan, KMGan, PYZhong, YTsyganov, KShochet, LRRyan, JStegeman, CAFugger, LReid, HHRossjohn, JHeeringa, PHoldsworth, SRPeleg, AYKitching, AR<p>Autoreactivity to myeloperoxidase (MPO) causes anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), with rapidly progressive glomerulonephritis. Here, we show that a <em>Staphylococcus aureus</em> peptide, homologous to an immunodominant MPO T-cell epitope (MPO<sub>409–428</sub>), can induce anti-MPO autoimmunity. The peptide (6PGD<sub>391–410</sub>) is part of a plasmid-encoded 6-phosphogluconate dehydrogenase found in some <em>S. aureus</em> strains. It induces anti-MPO T-cell autoimmunity and MPO-ANCA in mice, whereas related sequences do not. Mice immunized with 6PGD<sub>391–410</sub>, or with <em>S. aureus</em> containing a plasmid expressing 6PGD<sub>391–410</sub>, 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<sub>391–410</sub> is immunogenic in humans, as healthy human and AAV patient sera contain anti-6PGD and anti-6PGD<sub>391–410</sub> antibodies. Therefore, our results support the idea that bacterial plasmids might have a function in autoimmune disease.</p> |
| spellingShingle | 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 A plasmid-encoded peptide from Staphylococcus aureus induces anti-myeloperoxidase nephritogenic autoimmunity |
| title | A plasmid-encoded peptide from Staphylococcus aureus induces anti-myeloperoxidase nephritogenic autoimmunity |
| title_full | A plasmid-encoded peptide from Staphylococcus aureus induces anti-myeloperoxidase nephritogenic autoimmunity |
| title_fullStr | A plasmid-encoded peptide from Staphylococcus aureus induces anti-myeloperoxidase nephritogenic autoimmunity |
| title_full_unstemmed | A plasmid-encoded peptide from Staphylococcus aureus induces anti-myeloperoxidase nephritogenic autoimmunity |
| title_short | A plasmid-encoded peptide from Staphylococcus aureus induces anti-myeloperoxidase nephritogenic autoimmunity |
| title_sort | plasmid encoded peptide from staphylococcus aureus induces anti myeloperoxidase nephritogenic autoimmunity |
| work_keys_str_mv | AT ooijd aplasmidencodedpeptidefromstaphylococcusaureusinducesantimyeloperoxidasenephritogenicautoimmunity AT jiangjh aplasmidencodedpeptidefromstaphylococcusaureusinducesantimyeloperoxidasenephritogenicautoimmunity AT eggenhuizenpj aplasmidencodedpeptidefromstaphylococcusaureusinducesantimyeloperoxidasenephritogenicautoimmunity AT chuall aplasmidencodedpeptidefromstaphylococcusaureusinducesantimyeloperoxidasenephritogenicautoimmunity AT vantimmerenm aplasmidencodedpeptidefromstaphylococcusaureusinducesantimyeloperoxidasenephritogenicautoimmunity AT lohkl aplasmidencodedpeptidefromstaphylococcusaureusinducesantimyeloperoxidasenephritogenicautoimmunity AT osullivankm aplasmidencodedpeptidefromstaphylococcusaureusinducesantimyeloperoxidasenephritogenicautoimmunity AT ganpy aplasmidencodedpeptidefromstaphylococcusaureusinducesantimyeloperoxidasenephritogenicautoimmunity AT zhongy aplasmidencodedpeptidefromstaphylococcusaureusinducesantimyeloperoxidasenephritogenicautoimmunity AT tsyganovk aplasmidencodedpeptidefromstaphylococcusaureusinducesantimyeloperoxidasenephritogenicautoimmunity AT shochetlr aplasmidencodedpeptidefromstaphylococcusaureusinducesantimyeloperoxidasenephritogenicautoimmunity AT ryanj aplasmidencodedpeptidefromstaphylococcusaureusinducesantimyeloperoxidasenephritogenicautoimmunity AT stegemanca aplasmidencodedpeptidefromstaphylococcusaureusinducesantimyeloperoxidasenephritogenicautoimmunity AT fuggerl aplasmidencodedpeptidefromstaphylococcusaureusinducesantimyeloperoxidasenephritogenicautoimmunity AT reidhh aplasmidencodedpeptidefromstaphylococcusaureusinducesantimyeloperoxidasenephritogenicautoimmunity AT rossjohnj aplasmidencodedpeptidefromstaphylococcusaureusinducesantimyeloperoxidasenephritogenicautoimmunity AT heeringap aplasmidencodedpeptidefromstaphylococcusaureusinducesantimyeloperoxidasenephritogenicautoimmunity AT holdsworthsr aplasmidencodedpeptidefromstaphylococcusaureusinducesantimyeloperoxidasenephritogenicautoimmunity AT pelegay aplasmidencodedpeptidefromstaphylococcusaureusinducesantimyeloperoxidasenephritogenicautoimmunity AT kitchingar aplasmidencodedpeptidefromstaphylococcusaureusinducesantimyeloperoxidasenephritogenicautoimmunity AT ooijd plasmidencodedpeptidefromstaphylococcusaureusinducesantimyeloperoxidasenephritogenicautoimmunity AT jiangjh plasmidencodedpeptidefromstaphylococcusaureusinducesantimyeloperoxidasenephritogenicautoimmunity AT eggenhuizenpj plasmidencodedpeptidefromstaphylococcusaureusinducesantimyeloperoxidasenephritogenicautoimmunity AT chuall plasmidencodedpeptidefromstaphylococcusaureusinducesantimyeloperoxidasenephritogenicautoimmunity AT vantimmerenm plasmidencodedpeptidefromstaphylococcusaureusinducesantimyeloperoxidasenephritogenicautoimmunity AT lohkl plasmidencodedpeptidefromstaphylococcusaureusinducesantimyeloperoxidasenephritogenicautoimmunity AT osullivankm plasmidencodedpeptidefromstaphylococcusaureusinducesantimyeloperoxidasenephritogenicautoimmunity AT ganpy plasmidencodedpeptidefromstaphylococcusaureusinducesantimyeloperoxidasenephritogenicautoimmunity AT zhongy plasmidencodedpeptidefromstaphylococcusaureusinducesantimyeloperoxidasenephritogenicautoimmunity AT tsyganovk plasmidencodedpeptidefromstaphylococcusaureusinducesantimyeloperoxidasenephritogenicautoimmunity AT shochetlr plasmidencodedpeptidefromstaphylococcusaureusinducesantimyeloperoxidasenephritogenicautoimmunity AT ryanj plasmidencodedpeptidefromstaphylococcusaureusinducesantimyeloperoxidasenephritogenicautoimmunity AT stegemanca plasmidencodedpeptidefromstaphylococcusaureusinducesantimyeloperoxidasenephritogenicautoimmunity AT fuggerl plasmidencodedpeptidefromstaphylococcusaureusinducesantimyeloperoxidasenephritogenicautoimmunity AT reidhh plasmidencodedpeptidefromstaphylococcusaureusinducesantimyeloperoxidasenephritogenicautoimmunity AT rossjohnj plasmidencodedpeptidefromstaphylococcusaureusinducesantimyeloperoxidasenephritogenicautoimmunity AT heeringap plasmidencodedpeptidefromstaphylococcusaureusinducesantimyeloperoxidasenephritogenicautoimmunity AT holdsworthsr plasmidencodedpeptidefromstaphylococcusaureusinducesantimyeloperoxidasenephritogenicautoimmunity AT pelegay plasmidencodedpeptidefromstaphylococcusaureusinducesantimyeloperoxidasenephritogenicautoimmunity AT kitchingar plasmidencodedpeptidefromstaphylococcusaureusinducesantimyeloperoxidasenephritogenicautoimmunity |