Clinical associations and characterisation of antineutrophil cytoplasmic antibodies directed against bactericidal/permeability-increasing protein andazurocidin
T. Cooper et al., Clinical associations and characterisation of antineutrophil cytoplasmic antibodies directed against bactericidal/permeability-increasing protein andazurocidin, RHEUM INTL, 19(4), 2000, pp. 129-136
Bactericidal/permeability-increasing protein (BPI) and azurocidin (AZ) are
recently described target antigens of antineutrophil cytoplasmic antibodies
(ANCA). In this study, BPI-ANCA were demonstrated most often in patients w
ith ulcerative colitis (36/92, 39%), Crohn's disease (17/66, 26%) and cysti
c fibrosis (11/14, 79%), but also in patients with rheumatoid arthritis (8/
40, 20%), systemic lupus erythematosus (SLE) (111/65, 17%) and mixed connec
tive tissue disease (4/18, 22%). BPI-ANCA were also common in sera containi
ng antinuclear (ANA) (9/43, 21%) or antidouble-stranded (ds) DNA (7/28, 25%
) antibodies. There was no increased frequency of abnormal alpha(1)-antitry
psin (alpha(1)-AT) phenotypes in patients with BPI-ANCA, and BPI-ANCA were
not more common in individuals with an abnormal phenotype. The predominant
IgG subclasses were IgG1 and IgG3; IgA but not IgM was present. Both IgG an
d IgA BPI-ANCA were high affinity antibodies, and the affinity of IgG antib
odies did not change with time in the sera tested. Four of the five sera (8
0%) containing BPI-ANCA did not bind to denatured, reduced BPI, suggesting
that most BPI-ANCA recognised conformational epitopes. AZ-ANCA were demonst
rated in 2/11 patients (18%) with Wegener's granulomatosis, 3/12 (25%) with
cystic fibrosis and 3/14 (21%) with chronic active hepatitis. AZ-ANCA were
present in 5/25 sera (25%) with ANA, but the levels were only marginally e
levated. AZ-ANCA were uncommon in patients with inflammatory bowel and rheu
matological diseases, and in sera containing other autoantibodies. Again, t
here was no association with abnormal alpha(1)-AT phenotypes. BPI represent
s a major ANCA target antigen in patients with rheumatological as well as i
nflammatory bowel disease and cystic fibrosis, but AZ-ANCA are uncommon.