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Anti‐neutrophil cytoplasmic antibodies directed against the bactericidal/permeability‐increasing protein (BPI) in pediatric cystic fibrosis patients do not recognize N‐terminal regions important for the anti‐microbial and lipopolysaccharide‐binding activity of BPI
Author(s) -
Schultz Hendrik,
Csernok Elena,
Schuster Antje,
Schmitz Thomas S.,
Ernst Martin,
Gross Wolfgang L.
Publication year - 2000
Publication title -
pediatric allergy and immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.269
H-Index - 89
eISSN - 1399-3038
pISSN - 0905-6157
DOI - 10.1034/j.1399-3038.2000.00069.x
Subject(s) - cystic fibrosis , lipopolysaccharide binding protein , antibody , medicine , monoclonal antibody , immunology , epitope , lactoferrin , lipopolysaccharide , anti neutrophil cytoplasmic antibody , microbiology and biotechnology , pathology , biology , inflammation , acute phase protein , biochemistry , vasculitis , disease
This study was performed to examine the prevalence and clinical correlates of bactericidal/permeability‐increasing protein anti‐neutrophil cytoplasmic antibodies (BPI‐ANCA) in pediatric cystic fibrosis (CF) patients and to elucidate their possible role in CF pulmonary pathology. Sera of 27 CF patients were tested for ANCA by indirect immunofluorescence (IFT) and by enzyme‐linked immunosorbent assay (ELISA) for ANCA sub‐specificities. BPI‐ANCA were examined by using standard ELISA for BPI, lipopolysaccharide‐binding protein (LBP), and BPI/LBP fusion proteins to epitope map the main binding sites and look for cross‐reactivity with LBP. Pulmonary function and serum concentrations of total immunoglobulin G (IgG) were measured and infections were diagnosed. In addition, release of reactive oxygen species (ROS) by neutrophil granulocytes was measured after stimulation with monoclonal BPI‐ANCA. Using IFT, two patients showed atypical ANCA staining, six patients exhibited perinuclear ANCA staining, and no cytoplasmic ANCA staining was detected. Of 27 patients, 13 (48%) were BPI‐ANCA (IgG) positive, and three were also immunoglobulin A (IgA) BPI‐ANCA positive; one patient had ANCA against lactoferrin; and no proteinase 3 ANCA was detected in any of the patients. All BPI‐ANCA bound to the C‐terminal region of the molecule; none bound to the N‐terminus or to LBP. There was no significant correlation between clinical data and the occurence of BPI‐ANCA in this cross‐sectional study. Release of ROS from granulocytes was induced by monoclonal BPI‐ANCA. Activation of neutrophils and possible modulation of BPI‐mediated opsonophagocytosis and disposal of Gram‐negative bacteria and lipopolysaccharides by BPI‐ANCA raise the possibility that they contribute to pulmonary pathology in pediatric CF patients but intervention longitudinal studies in large groups of patients are needed to establish a causative association.