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

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 wellcharacterized 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. Chronic obstructive pulmonary disease (COPD) is a debilitating disease that is the fourth most common cause of death in the United States (2, 4). Bacteria play several potential roles in the course and pathogenesis of the disease (20). Selected bacteria colonize the lower airways of adults with COPD and release potent inflammatory molecules that contribute to the airway inflammation that is a hallmark of COPD (6,7,13,21,22). Patients with COPD acquire and clear bacteria from the respiratory tract continuously. Little is known about the immune responses that mediate this turnover of bacteria. The course of COPD is characterized by intermittent episodes of worsening of symptoms, known as exacerbations. It is estimated that approximately half of the exacerbations are caused by bacterial infection (20,23,24). Nontypeable Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae are the most frequent bacterial causes of exacerbations of COPD (19,20).Studies involving the molecular typing of isolates recovered from sputum samples collected prospectively have begun to elucidate the dynamics of colonization and infection by M. catarrhalis in the setting of COPD (15). M. catarrhalis likely causes approximately 10% of exacerbations of COPD, accounting for approximately 2 to 4 million episodes annually. When adults with COPD acquire M. catarrhalis, the organism is cleared efficiently from the respiratory tract after a relatively short duration of carriage (median time, 34 days). Patients then develop strain-specific protection against reacquisition of the same strain (15). This observation that humans develop apparent protective responses to M. catarrhalis after clearing it from the respiratory tract provides the opportunity to begin to understand protective immune responses. The majority of patients develop serum immunoglobulin G (IgG) and/or sputum IgA responses to their homologous infecting isolate of M. catarrhalis, as demonstrated by whole-cell enzyme-linked immunosorbent assay and flow cytometry assays (3, 15). Further analysis of serum immunoglobulins in this cohort has revealed...

Temporal development of the humoral immune response to surface antigens of Moraxella catarrhalis in young infants

“…It is also found in small amounts in blood [32]. This may explain the relatively low levels of IgA found in this study, as serum antigenspecific IgA levels were measured and not secretory IgA [33][34].…”

Age-related genotypic and phenotypic differences in Moraxella catarrhalis isolates from children and adults presenting with respiratory disease in 2001–2002

“…All of these vaccine candidates have been associated with the production of antibody (Bakri et al, 2002;Faden, 1995;Meier et al, 2003;Murphy et al, 2003Murphy et al, , 2005b, although little is known about the frequency and expression of the corresponding genes in global isolates recovered from children and adults.…”

A Conserved Tetranucleotide Repeat Is Necessary for Wild-Type Expression of the Moraxella catarrhalis UspA2 Protein

“…In a recent survey of nasopharyngeal isolates from young children in Greece, a uspA2 gene or the closely related uspA2H gene was detected in 100% of the 108 strains tested (38). UspA2 appears to be a target for antibodies that develop in patients with chronic obstructive pulmonary disease (43,44), and antibodies to this protein can also be detected in very young children colonized with M. catarrhalis (37) and in serum and saliva from healthy individuals (13,51).…”