Otitis media in children: Local immune response to nontypeable Haemophilus influenzae

Abstract

Twenty children experienced 30 episodes of otitis media with effusion due to nontypeable (NT) Haemophilus influenzae in the first 2 years of life. The local and systemic immune responses to homologous strains of NT H. influenzae were determined by an immunodot assay. Strain-specific immunoglobulin G (IgG) antibody predominated in the middle ear fluid (MEF). It was detected in 91% of the children, compared with IgM in 48% (P < 0.005), IgA in 52% (P < 0.005), and secretory IgA in 18% (P < 0.005). The titer (log2) of NT H. influenzae-specific IgG antibody (mean standard error, 8.2 + 0.1) exceeded the titers of IgM (3.4 0.1), IgA (3.7 0.1), and secretory IgA (1.2 + 0.3). NT H. influenzae-specific antibody was detected exclusively in MEFs of individuals who possessed homologous serum antibody. Although antibody titers in MEF declined over time, serum antibody titers remained stable. These data suggest that immunity to NT H. influenzae in the middle ear, in part, reflects systemic immunity. Whereas local antibody disappears after resolution of the infection, systemic antibody persists.Otitis media with effusion (OME) is among the most common illnesses that affect young children. Approximately 60 to 70% of children experience OME during the first 3 years of life, and at least 40% of them experience more than one episode (26). The incidence of OME is highest in the first 2 years of life and then declines (10). Presumably, immunity plays a role in the reduction of the frequency of OME.Three bacterial species-Streptococcus pneumoniae, nontypeable (NT) Haemophilus influenzae, and Branhamella catarrhalis-account for the majority of identifiable bacterial causes of acute OME (2,3,(18)(19)(20). NT Haemophilus influenzae is responsible for a major share of recurrent episodes of OME (9,11). Recent studies have suggested that NT H. influenzae consists of many different strains that may be characterized by their outer membrane proteins (13-16). Immunity to NT H. influenzae appears to be strain specific and directed to the outer membrane proteins (1,5,6,8,15,17). Susceptibility and resistance to the development of NT H. influenzae OME have been associated with the presence and absence of serum bactericidal antibody (1,8,21). Less is known about the role of local immunity in NT H. influenzae OME.The present study was designed to examine the local development of immunoglobulin G (IgG), IgM, IgA, and secretory IgA (sIgA) antibodies to homologous strains of NT H. influenzae in the middle ear during active infection. The study also analyzed humoral response to NT H. influenzae over a prolonged period of convalescence. MATERIALS AND METHODSGeneral design. A total of 220 children were enrolled in a prospective study of otitis media. At enrollment, 39% were s6 months old, 32% were 7 to 12 months old, and 29% were >12 months old. At the time of entry into the study, 32% had experienced no OME, 51% had had one to five episodes of OME, and 17% had had more than five episodes of OME. During 3 years of monitoring the children, 320 tympanocen-*...