title: Antineutrophil cytoplasmic autoantibodies (ANCA) in children with cystic fibrosis.
abstract: Anti-neutrophil cytoplasmic antibodies (ANCA) represent a useful diagnostic tool in patients with small vessel vasculitis. Circulating ANCA specific for bactericidal/permeability increasing protein (BPI) have been recently reported in adult patients with cystic fibrosis (CF), an autosomal recessive disorder caused by mutations in the cystic fibrosis transmembrane regulator (CFTR) gene with consequent impaired function of a transmembrane chloride channel. To contribute to the better understanding of the significance of ANCA in this disease, we investigated ANCA presence and antigenic specificity in children with CF. Results were correlated with clinical status, immunological data, age and genotype. The indirect immunofluorescence pattern of a total of 71 children with CF indicated that 31 were c-ANCA positive, while seven were p-ANCA positive. In further ELISA studies of ANCA antigenic specificity, 51 out of 66 investigated samples were positive for BPI, and 14 out of 28 were positive for proteinase 3 (PR3). We found an association between levels of antibodies against PR3 with age and Pseudomonas infection. We did not, however, find any correlation between CFTR genotypes, Pseudomonas infection or paediatric parameters and the level of anti-BPI antibodies. High positivity of anti-BPI antibodies were seen even among the youngest CF patients, before the development of clinical signs of CF, indicating that formation of ANCA might be a very early event in the disease. Both anti-BPI and anti-PR3 antibodies may play a significant, although variable role, in the pathogenesis of CF.
authors.affiliation: Institute of Immunology, University Hospital Motol, Charles University, Prague, Czech Republic. Anna.Sediva@lfmotol.cuni.cz
authors.forename: A
authors.initials: A
authors.lastname: Sedivá
authors.forename: J
authors.initials: J
authors.lastname: Bartůnková
authors.forename: I
authors.initials: I
authors.lastname: Kolárová
authors.forename: O
authors.initials: O
authors.lastname: Hrusák
authors.forename: V
authors.initials: V
authors.lastname: Vávrová
authors.forename: M
authors.initials: M
authors.lastname: Macek
authors.forename: C M
authors.initials: CM
authors.lastname: Lockwood
authors.forename: A C
authors.initials: AC
authors.lastname: Dunn
mesh_terms: D000293:Adolescent; D000367:Age Factors; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000097:blood / Q000276:immunology*; D000918:Antibody Specificity; D023181:Antimicrobial Cationic Peptides; D001324:Autoantigens / Q000276:immunology*; D001327:Autoimmune Diseases / Q000209:etiology / Q000235:genetics / Q000276:immunology*; D001798:Blood Proteins / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000097:blood / Q000150:complications / Q000235:genetics / Q000276:immunology*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D005838:Genotype; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007223:Infant; D008297:Male; D008565:Membrane Proteins; D053146:Myeloblastin; D011552:Pseudomonas Infections / Q000097:blood / Q000209:etiology / Q000276:immunology; D012697:Serine Endopeptidases / Q000276:immunology*; D014657:Vasculitis / Q000209:etiology / Q000276:immunology*
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; D023181:Antimicrobial Cationic Peptides; D001324:Autoantigens; D001798:Blood Proteins; C505032:CFTR protein, human; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D008565:Membrane Proteins; C021623:bactericidal permeability increasing protein; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D012697:Serine Endopeptidases; D053146:Myeloblastin