scholarly journals Antigenic Specificity of the Mucosal Antibody Response to Moraxella catarrhalis in Chronic Obstructive Pulmonary Disease

2005 ◽  
Vol 73 (12) ◽  
pp. 8161-8166 ◽  
Author(s):  
Timothy F. Murphy ◽  
Aimee L. Brauer ◽  
Christoph Aebi ◽  
Sanjay Sethi
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Immune Response ◽  
Antibody Response ◽  
Pulmonary Disease ◽  
Moraxella Catarrhalis ◽  
Surface Protein ◽  
Antigenic Specificity ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Mucosal Antibody

ABSTRACT Moraxella catarrhalis is an important human mucosal pathogen causing otitis media in children and lower respiratory tract infection in adults with chronic obstructive pulmonary disease (COPD). Little is known about the mucosal antibody response to M. catarrhalis in adults with COPD. In this study, 10 pairs of well-characterized sputum supernatant samples from adults with COPD who had acquired and subsequently cleared M. catarrhalis from their respiratory tracts were studied in detail in an effort to begin to elucidate potentially protective immune responses. Flow cytometry analysis was used to study the distribution of immunoglobulin isotypes in paired preacquisition and postclearance sputum samples. The results showed that immunoglobulin A (IgA) is the predominant M. catarrhalis-specific immunoglobulin isotype and that the sputum IgA contains a secretory component, indicating that it is locally produced at the mucosal site. Most patients made new sputum IgA responses to the adhesins UspA1 and Hag, along with the surface protein UspA2. A smaller proportion of patients made new sputum IgA responses to the iron-regulated proteins TbpB and CopB and to lipooligosaccharide. These results have important implications in understanding the mucosal immune response to M. catarrhalis in the setting of COPD and in elucidating the elements of a protective immune response.

scholarly journals Identification of Domains of the Hag/MID Surface Protein Recognized by Systemic and Mucosal Antibodies in Adults with Chronic Obstructive Pulmonary Disease following Clearance of Moraxella catarrhalis

2009 ◽  
Vol 16 (5) ◽  
pp. 653-659 ◽  
Author(s):  
Eric R. LaFontaine ◽  
Lauren E. Snipes ◽  
Brian Bullard ◽  
Aimee L. Brauer ◽  
Sanjay Sethi ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Respiratory Tract ◽  
Pulmonary Disease ◽  
Moraxella Catarrhalis ◽  
Surface Protein ◽  
Antibody Responses ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Recombinant Peptide ◽  
Mucosal Antibody

ABSTRACT Moraxella catarrhalis is a common cause of respiratory tract infection in the setting of chronic obstructive pulmonary disease (COPD). Adults with COPD acquire and clear strains of M. catarrhalis from the respiratory tract continuously and develop strain-specific protection following clearance of a strain. In previous work, we identified Hag/MID (Moraxella immunoglobulin D-binding protein), a large multifunctional surface protein that acts as an adhesin and hemagglutinin, as a target of antibody responses in adults with COPD after clearance of M. catarrhalis. The goal of the present study was to characterize the domains of Hag/MID to which humans make antibodies, including both systemic and mucosal antibody responses. Analysis of recombinant peptide constructs, which spanned the M. catarrhalis strain O35E Hag/MID protein, with well-characterized serum and sputum samples revealed that most adults with COPD made antibodies directed toward a region of the molecule bounded by amino acids 706 to 863. Serum immunoglobulin G (IgG) and IgA purified from sputum both recognized the same domain. Some flanking sequence of this fragment was necessary for the epitope(s) in this region to maintain its conformation to bind human antibodies. These results reveal that humans consistently generate both systemic and mucosal antibody responses to an immunodominant region of the Hag/MID molecule, which was previously shown to overlap with several biologically relevant domains, including epithelial cell adherence, IgD binding, collagen binding, and hemagglutination.

scholarly journals Human Immune Response to Outer Membrane Protein CD of Moraxella catarrhalis in Adults with Chronic Obstructive Pulmonary Disease

2003 ◽  
Vol 71 (3) ◽  
pp. 1288-1294 ◽  
Author(s):  
Timothy F. Murphy ◽  
Charmaine Kirkham ◽  
Dai-Fang Liu ◽  
Sanjay Sethi
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Immune Response ◽  
Membrane Protein ◽  
Outer Membrane ◽  
Pulmonary Disease ◽  
Outer Membrane Protein ◽  
Moraxella Catarrhalis ◽  
Enzyme Linked Immunosorbent Assay ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease

ABSTRACT Moraxella catarrhalis is a common cause of lower respiratory tract infection in adults with chronic obstructive pulmonary disease (COPD). The antibody response to outer membrane protein (OMP) CD, a highly conserved surface protein of M. catarrhalis under consideration as a vaccine antigen, was studied in adults with COPD following 40 episodes of infection or colonization. Following infection or colonization, 9 of 40 patients developed new serum immunoglobulin G (IgG) to OMP CD, as measured by enzyme-linked immunosorbent assay. Adsorption assays revealed that a proportion of the serum IgG was directed toward surface-exposed epitopes on OMP CD in six of the nine patients who developed new IgG to OMP CD. Immunoblot assays with fusion peptide constructs indicated that the new antibodies that developed after infection or colonization recognized conformational epitopes, particularly in the carboxy region of the protein. Three of 28 patients developed new mucosal IgA to OMP CD in sputum supernatants. This study establishes that OMP CD is a target of a systemic and mucosal immune response following infection and colonization in some patients with COPD.

scholarly journals Identification of Surface Antigens of Moraxella catarrhalis as Targets of Human Serum Antibody Responses in Chronic Obstructive Pulmonary Disease

2005 ◽  
Vol 73 (6) ◽  
pp. 3471-3478 ◽  
Author(s):  
Timothy F. Murphy ◽  
Aimee L. Brauer ◽  
Christoph Aebi ◽  
Sanjay Sethi
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Respiratory Tract ◽  
Pulmonary Disease ◽  
Moraxella Catarrhalis ◽  
Outer Membrane Proteins ◽  
Serum Antibody ◽  
Antibody Responses ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Tract Infections

ABSTRACT Moraxella catarrhalis is an important respiratory tract pathogen, causing otitis media in children and lower respiratory tract infections in adults with chronic obstructive pulmonary disease (COPD). Adults with COPD make antibody responses to M. catarrhalis following infection, but little is known about the identity of the antigens to which these antibodies are directed. In this study, 12 serum samples obtained from adults with COPD who had cleared M. catarrhalis from the respiratory tract following infection and who had developed new serum immunoglobulin G (IgG) to their infecting strain were subjected to a series of assays to identify the antigens to which potentially protective antibodies were directed. Sera were adsorbed with intact bacterial cells, and antibodies were eluted from the surfaces of the bacteria. Analysis by flow cytometry established that adsorption and elution effectively detected antibodies specifically directed to surface-exposed epitopes. Immunoblot assays of adsorbed and eluted serum fractions were performed with purified outer membranes and purified lipooligosaccharide of homologous infecting strains and with a series of mutants deficient in expression of individual outer membrane proteins (OMPs). While heterogeneity in antibody responses among individuals was observed, five major OMPs, UspA1, UspA2, Hag, TbpB, and OMP CD, were identified as targets of antibodies to surface epitopes in the majority of adults with COPD who cleared the organism. These results have important implications in understanding human immune responses to M. catarrhalis and in elucidating the elements of a protective immune response.

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