Bactericidal/permeability-increasing protein (BPI) is an important antigen for anti-neutrophil cytoplasmic autoantibodies (ANCA) in vasculitis

Abstract

SUMMARYIndirect immunofluorescence (IIF) techniques have shown that ANCA are useful serological markers for some small vessel vasculitides, and ELISA assays, using purified molecules as solidphase ligand, have helped to identify proteinase 3 (PR3) and myeloperoxidase (MPO) as two of the major ANCA antigens. There remain a substantial number of serum samples, which are positive by IIF, yet recognize neither PR3 nor MPO (double-negative samples). We found, by Western blot analysis of soluble neutrophil granule proteins, that certain ofthese double-negative samples recognized a 55-kD doublet of which the first eight residues shared N-terminal amino acid sequence homology with BPI, a potent antibiotic towards Gram-negative bacteria. We developed a simple, quick and robust two-step immunobiochemical method to purify BPI. This was then employed to detect anti-BPI autoantibodies by ELISA and Western blot analysis. We tested 100 double-negative samples and 400 consecutive new samples sent for routine ANCA testing in the anti-BPI ELISA. We found that 45 of the 100 double-negative and 44 of the 400 new routine samples recognized BPI. By Western blot analysis 20/20 positive anti-BPI samples blotted the 55-kD protein. Inhibition assays confirmed the specificity of binding. Review of the 89 anti-BPI-positive patients showed a male dominance (M: F ratio 55:34), a mean age of 60 4 years and clinical diagnoses ranging from organ limited vasculitis to widespread systemic vasculitis.

Pathogenesis and clinical manifestations of chronic colonization by Pseudomonas aeruginosa and its biofilms in the airway tract

“…LBP acts to disperse LPS aggregates and to deliver LPS to the cellular CD14/TLR complexes, but BPI increases the size of BPI-LPS complexes in a BPI concentrationdependent manner and inhibits LPS activity. 208,209 Zhao et al 210 identifi ed anti-neutrophil cytoplasmic autoantibody against BPI (BPI-ANCA) in a patient with vasculitis. The serum titer of BPI-ANCA was positive in 91% of patients with CF, 14 94% of patients with DPB, 15 62% of patients with bronchiectasis with chronic infection, and approximately 50% of patients with old active pulmonary tuberculosis, 211 but the titer was not positive in patients with acute lung infection.…”

The bactericidal/permeability-increasing protein (BPI) in infection and inflammatory disease

“…BPI was also first described as an ANCA target antigen in vasculitides [113,114]. However, it soon became apparent that BPI is a target of ANCA in a variety of diseases of different etiologies like cystic fibrosis (CF), inflammatory bowel diseases (IBD), reactive arthritis (ReA), HIV, the recently discovered peptide transporter complex associated with antigen presentation (TAP) deficiency [16][17][18]113,115] and chronic obstructive pulmonary disease (COPD, Schultz, H. and Murphy, T.F., unpublished observation). Thus, BPI-ANCA could not be used as a disease-specific seromarker as PR3-ANCA is for Wegener's granulomatosis.…”

Systemic Vasculitis Associated with Anti-Neutrophil Cytoplasmic Antibodies against Bactericidal/Permeability Increasing Protein

“…These are observed less frequently than MPO-and PR3-ANCAs and are known to be minor ANCAs (x-ANCA). BPI-ANCA was reported by Zhao et al to be a x-ANCA in 1995 (9). BPI is a protein that is abundantly found in azurophilic granules of neutrophils and plays an important role in antibacterial defense against Gram-negative bacteria.…”