Frequency of anti-bactericidal/permeability-increasing protein (BPI) and anti-azurocidin in patients with renal disease.
The major subtypes of anti-neutrophil cytoplasmic antibodies (ANCA) detected by indirect immunofluorescence assay (IFA) are P-ANCA and C-ANCA. In patients with vasculitis, myeloperoxidase (MPO) is the major P-ANCA antigen and proteinase 3 (PR3) is the major C-ANCA antigen. BPI and azurocidin, which are also called 57-kD cationic antimicrobial protein (CAP 57) and 37-kD cationic antimicrobial protein (CAP 37), respectively, have been proposed as less frequent target antigens for C-ANCA and P-ANCA. In patients with renal disease, we determined the frequency of antibodies against BPI and azurocidin. By IFA on alcohol-fixed neutrophils, monoclonal and polyclonal anti-BPI antibodies produced a C-ANCA pattern, whereas rabbit anti-azurocidin antibody produced a P-ANCA pattern. By ELISA, sera from 229 P-ANCA-positive patients, 99 C-ANCA-positive patients and 48 ANCA-negative (by IFA) patients with renal biopsies were tested for reactivity with recombinant human BPI and purified human azurocidin. Of these sera, 17.5% of P-ANCA, 30.3% of C-ANCA and 20.8% of IFA-ANCA-negative sera were positive for anti-BPI; and 8.3% of P-ANCA, 3.0% of C-ANCA and 8.3% of IFA-ANCA-negative sera were positive for anti-azurocidin. There was no statistical difference in frequency of anti-BPI between pauci-immune necrotizing and crescentic glomerulonephritis (NCGN) and other glomerular disease (OGD), and there was a lower frequency of anti-azurocidin in NCGN samples than in OGD samples. By Western blot, anti-BPI-positive sera reacted with a 57-kD BPI band and anti-azurocidin-positive sera with a 29-kD azurocidin band. In conclusion, there is a low frequency of anti-BPI and anti-azurocidin antibodies in ANCA-positive patient sera; however, this does not correlate with NCGN, which is a marker for ANCA-associated small vessel vasculitis, and a similar positivity is found in IFA-ANCA-negative patients with renal disease. Therefore, serologic detection of anti-BPI and anti-azurocidin is not diagnostically specific in patients with renal disease.
Yang
J J
JJ
Department of Medicine, University of North Carolina at Chapel Hill 27599-7155, USA.
Tuttle
R
R
Falk
R J
RJ
Jennette
J C
JC
D000595:Amino Acid Sequence; D019268:Antibodies, Antineutrophil Cytoplasmic; D023181:Antimicrobial Cationic Peptides; D001323:Autoantibodies / Q000097:blood*; D001770:Blood Bactericidal Activity / Q000276:immunology*; D001798:Blood Proteins / Q000276:immunology* / Q000302:isolation & purification; D015153:Blotting, Western; D002352:Carrier Proteins; D004797:Enzyme-Linked Immunosorbent Assay; D019084:Fluorescent Antibody Technique, Indirect; D005921:Glomerulonephritis / Q000276:immunology / Q000473:pathology; D006801:Humans; D007674:Kidney Diseases / Q000276:immunology* / Q000473:pathology; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D011994:Recombinant Proteins / Q000737:chemistry
C062991:AZU1 protein, human; D019268:Antibodies, Antineutrophil Cytoplasmic; D023181:Antimicrobial Cationic Peptides; D001323:Autoantibodies; D001798:Blood Proteins; D002352:Carrier Proteins; D008565:Membrane Proteins; D011994:Recombinant Proteins; C021623:bactericidal permeability increasing protein