title: Nonopsonic antibodies in cystic fibrosis. Pseudomonas aeruginosa lipopolysaccharide-specific immunoglobulin G antibodies from infected patient sera inhibit neutrophil oxidative responses.
abstract: Antibody opsonins from cystic fibrosis (CF) patients were investigated using nonmucoid and mucoid lipopolysaccharide (LPS) immunotype 1 Pseudomonas aeruginosa as bacterial ligands and PMN phagocytes. CF sera were compared to normal sera, polyvalent PA LPS hyperimmune globulin, and isotype switch variant monoclonal antibodies (MAbs) specific for type 1 PA LPS. Sera from PA-infected CF patients (CF PA+) had elevated levels of PA LPS and alginate IgG antibodies and promoted significantly greater antibody-dependent PMN chemiluminescence responses than sera from uninfected CF patients (CF PA-) or normal human sera (NHS). After adjustment for autologous IgG PA LPS antibody content, however, CF PA+ sera had less antibody-dependent opsonic activity than sera from CF PA- patients (P less than 0.025) or NHS (P less than 0.0025), suggesting qualitative opsonic defects of IgG PA LPS antibodies in CF PA+ sera. Antigen-specific immunoprecipitation of PA LPS antibodies enhanced opsonization by 40% of CF PA+ sera while uniformly reducing that from CF PA- sera (P less than 0.01), indicating LPS-specific nonopsonic antibodies in some CF PA+ sera. Alginate antibodies were not critical opsonins in most uninfected CF patient sera. PA LPS IgG antibodies isolated by immunoaffinity chromatography from NHS, hyperimmune globulin, and CF PA- sources were opsonic and had greater activity at equal antigen-binding concentration than identical antibodies isolated from infected CF patients (P less than 0.01-0.05); the majority of isolates from CF PA+ sera did not promote PMN oxidative responses above nonopsonic baseline. A potential isotypic basis for these findings was supported by differences in PMN responses to PA opsonized with MAbs of identical specificity but differing isotypes. PA LPS-specific IgG antibodies inhibiting PMN oxidative responses in infected patient sera demonstrate antigen-specific immunomodulation of host responses by chronic bacterial parasitism in CF, which may play a role in the pathophysiology of lung disease.
authors.affiliation: Department of Pediatrics, Stanford University Medical School, Palo Alto, California.
authors.forename: I
authors.initials: I
authors.lastname: Eichler
authors.forename: L
authors.initials: L
authors.lastname: Joris
authors.forename: Y P
authors.initials: YP
authors.lastname: Hsu
authors.forename: J
authors.initials: J
authors.lastname: Van Wye
authors.forename: R
authors.initials: R
authors.lastname: Bram
authors.forename: R
authors.initials: R
authors.lastname: Moss
mesh_terms: D000907:Antibodies, Bacterial / Q000032:analysis / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology; D000918:Antibody Specificity; D003550:Cystic Fibrosis / Q000150:complications* / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis / Q000276:immunology*; D007700:Kinetics; D008070:Lipopolysaccharides / Q000276:immunology*; D008163:Luminescent Measurements; D009504:Neutrophils / Q000276:immunology*; D009895:Opsonin Proteins / Q000276:immunology*; D010084:Oxidation-Reduction; D011552:Pseudomonas Infections / Q000150:complications* / Q000276:immunology; D011550:Pseudomonas aeruginosa / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D008070:Lipopolysaccharides; D009895:Opsonin Proteins