Ac. Dunn et al., Anti-neutrophil cytoplasmic autoantibodies (ANCA) to bactericidal/permeability-increasing (BPI) protein recognize the carboxyl terminal domain, J INFECTION, 39(1), 1999, pp. 81-87
Objectives: to identify the region of bactericidal/permeability-increasing
protein (BPI) recognized by anti-BPI ANCA,
Methods: sera from 140 patients with a variety of clinical diagnoses (20 sy
stemic vasculitis, 12 cystic fibrosis, 22 bronchiectasis/chronic obstructiv
e airways disease, three diabetes mellitus, 13 chronic renal failure, 12 pr
imary sclerosing cholangitis, eight ulcerative colitis, three Crohn's disea
se, seven cancer, and 40 other or unknown diagnoses) known to be reactive a
gainst native (nBPI), were screened by solid phase enzyme linked immunosorb
ent assay (ELISA) against a panel of recombinant fusion proteins; holo BPI
(rBPI), recombinant lipopolysaccharide binding protein (rLBP), an N-termina
l fragment of rBPI (rBP121) and 'fusion' proteins containing the C- or N-te
rminal ends of BPI spliced with N- or C-ends of LBP, respectively.
Results: a strong correlation was seen between the deg;ree of reactivity to
rBPI and the BPI C-terminal fusion protein, r = 0.69, P < 0.001, as well a
s between nBPI and rBPI protein, r = 0.55, P < 0.001, but not between nBPI
and the N-terminal region of EPI (rBPI21), or proteins containing only the
N-terminal fragment. Binding to proteins containing the BPI C-terminus was
confirmed to be specific by fluid phase inhibition ELISA and Western blot a
nalyses.
Conclusions: together these data suggest that circulating autoantibodies to
BPI from patients with different diseases recognize the C-terminal region
of BPI.