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

Area of Science:

• Immunology
• Microbiology
• Nephrology

Background:

• Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is an autoimmune condition often linked to autoreactivity against myeloperoxidase (MPO).
• The precise triggers for MPO-specific autoimmunity in AAV remain incompletely understood, prompting investigation into external factors.

Purpose of the Study:

• To investigate whether a bacterial peptide from Staphylococcus aureus, sharing homology with an MPO T-cell epitope, can induce anti-MPO autoimmunity.
• To determine if this bacterial mimicry can lead to the development of ANCA-associated vasculitis in a preclinical model.

Main Methods:

• Identification of a Staphylococcus aureus peptide (6PGD391-410) homologous to the MPO409-428 T-cell epitope.
• Immunization of mice with the 6PGD391-410 peptide or S. aureus strains expressing it.
• Assessment of T-cell responses, autoantibody production (anti-MPO, anti-6PGD), and development of glomerulonephritis.

Main Results:

• The 6PGD391-410 peptide induced MPO-specific T-cell autoimmunity and anti-MPO autoantibodies in mice.
• Mice immunized with the peptide or bacteria developed glomerulonephritis when MPO was present in glomeruli.
• Human sera from healthy individuals and AAV patients showed reactivity against the 6PGD391-410 peptide, indicating cross-reactivity.

Conclusions:

• A bacterial peptide from Staphylococcus aureus can mimic a key MPO epitope, triggering autoimmune responses relevant to ANCA-associated vasculitis.
• These findings implicate bacterial plasmids and molecular mimicry as potential contributors to the pathogenesis of MPO-ANCA vasculitis.
• The immunogenicity of the bacterial peptide in humans suggests a potential role in the initiation or exacerbation of autoimmune disease.