title: Clinical associations and characterisation of antineutrophil cytoplasmic antibodies directed against bactericidal/permeability-increasing protein and azurocidin.
abstract: 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 with ulcerative colitis (36/92, 39%), Crohn's disease (17/66, 26%) and cystic fibrosis (11/14, 79%), but also in patients with rheumatoid arthritis (8/40, 20%), systemic lupus erythematosus (SLE) (111/65, 17%) and mixed connective tissue disease (4/18, 22%). BPI-ANCA were also common in sera containing antinuclear (ANA) (9/43, 21%) or antidouble-stranded (ds) DNA (7/28, 25%) antibodies. There was no increased frequency of abnormal alpha1-antitrypsin (alphal1AT) 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 and IgA BPI-ANCA were high affinity antibodies, and the affinity of IgG antibodies did not change with time in the sera tested. Four of the five sera (80%) containing BPI-ANCA did not bind to denatured, reduced BPI, suggesting that most BPI-ANCA recognised conformational epitopes. AZ-ANCA were demonstrated 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 elevated. AZ-ANCA were uncommon in patients with inflammatory bowel and rheumatological diseases, and in sera containing other autoantibodies. Again, there was no association with abnormal alpha1-AT phenotypes. BPI represents a major ANCA target antigen in patients with rheumatological as well as inflammatory bowel disease and cystic fibrosis, but AZ-ANCA are uncommon.
authors.affiliation: University Department of Medicine, Austin and Repatriation Medical Centre, Heidelberg, Australia.
authors.forename: T
authors.initials: T
authors.lastname: Cooper
authors.forename: J
authors.initials: J
authors.lastname: Savige
authors.forename: L
authors.initials: L
authors.lastname: Nassis
authors.forename: B
authors.initials: B
authors.lastname: Paspaliaris
authors.forename: P
authors.initials: P
authors.lastname: Neeson
authors.forename: J
authors.initials: J
authors.lastname: Neil
authors.forename: K R
authors.initials: KR
authors.lastname: Knight
authors.forename: M
authors.initials: M
authors.lastname: Daskalakis
authors.forename: J C
authors.initials: JC
authors.lastname: Doery
mesh_terms: D019268:Antibodies, Antineutrophil Cytoplasmic / Q000097:blood* / Q000276:immunology*; D023181:Antimicrobial Cationic Peptides; D001323:Autoantibodies / Q000097:blood; D001327:Autoimmune Diseases / Q000097:blood / Q000276:immunology; D001798:Blood Proteins / Q000276:immunology* / Q000378:metabolism; D002352:Carrier Proteins / Q000276:immunology* / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006801:Humans; D007136:Immunoglobulins / Q000097:blood; D008565:Membrane Proteins; D010641:Phenotype; D000515:alpha 1-Antitrypsin / Q000235:genetics / Q000276:immunology
chemical_list: C062991:AZU1 protein, human; D019268:Antibodies, Antineutrophil Cytoplasmic; D023181:Antimicrobial Cationic Peptides; D001323:Autoantibodies; D001798:Blood Proteins; D002352:Carrier Proteins; D007136:Immunoglobulins; D008565:Membrane Proteins; D000515:alpha 1-Antitrypsin; C021623:bactericidal permeability increasing protein