ANCA against the bactericidal/permeability increasing protein (BPI-ANCA) can compromise the antibiotic function of BPI in a Wegener's granulomatosis patient

Area of Science:

• Immunology
• Rheumatology
• Microbiology

Background:

• Wegener's granulomatosis (WG) is a systemic vasculitis often associated with anti-neutrophil cytoplasmic antibodies (ANCA).
• While PR3-ANCA is the most common ANCA subtype in WG, other ANCA specificities can occur.
• Pulmonary involvement is a common and serious manifestation of WG.

Observation:

• A 54-year-old patient with WG and PR3-ANCA at diagnosis experienced a pulmonary relapse with subglottic stenosis.
• During relapse, PR3-ANCA was undetectable, but bactericidal/permeability increasing protein (BPI)-ANCA was present.
• Bronchoalveolar lavage identified Gram-negative bacterial infection.

Findings:

• The patient's IgG during relapse inhibited the antimicrobial activity of BPI in vitro, recognizing its bioactive N-terminal portion.
• This inhibition was not observed with IgG from before diagnosis or after remission.
• BPI-ANCA disappeared following successful antibiotic and immunosuppressive treatment (cyclophosphamide and infliximab).

Implications:

• BPI-ANCA may contribute to pulmonary relapses in WG by impairing bacterial clearance, particularly in the absence of PR3-ANCA.
• This suggests a novel pathogenic mechanism where ANCA against antimicrobial proteins can exacerbate inflammation.
• Targeting BPI-ANCA or enhancing BPI function could be potential therapeutic strategies in specific WG relapses.