Development of respiratory mucosal tolerance during Haemophilus influenzae type B infection in infancy

Abstract

Groups of patients with different forms of infection with Haemophilus influenzae type B (Hib), namely meningitis, epiglottitis, arthritis, and periorbital cellulitis, were evaluated for the appearance of serum IgG, IgA, IgM, and nasopharyngeal secretory (NPS) IgA (SIgA) antibody response to Hib capsular antigen at various intervals after the onset of clinical illness, by using an indirect enzyme-linked immunosorbent assay. The serum immune response was characterized by its predictable absence in infants under 23 mo of age, and in those with meningitis who, regardless of age, had high levels of circulating antigen. On the other hand, antibody response was frequently detected in the serum of older infants. Significantly, however, the appearance of SIgA antibody was demonstrated in virtually all patients with Hib infections under 23 mo of age. In addition, a positive correlation was observed between the concentration of antigen NPS, the level of SIgA activity in the NPS, and the absence of antibody response in the serum. These observations are strikingly similar to the development of systemic hyporesponsiveness (oral tolerance) observed after oral administration of certain infectious or nonreplicating antigens in experimental animals. It is suggested that similar mechanisms may underlie the immunologic abnormalities observed in the serum antibody response in infants with Hib meningitis.