Class and subclass antibodies to Haemophilus influenzae type b capsule: Comparison of invasive disease and natural exposure

Recently, the role of immunoglobulin G (IgG) subclasses in the immune responses to organisms with polysaccharide capsules, particularly Haemophilus influenzae type b, has been of interest. We developed assays to measure IgG2- and IgG4-specific antibodies to the polyribosylribitol phosphate (PRP) polysaccharide antigen of H. influenzae type b and demonstrated that these assays were subclass specific. Relative levels of subclass-specific antibody were assayed in serum from 30 Alaskan Eskimo children who had invasive H. influenzae type b disease and 30 healthy controls that were matched for age and village of residence. We also measured total PRP antibody and total serum IgG4. The group with invasive H. influenzae type b disease had a significantly higher mean level of IgG4-specific PRP antibody than did the controls (P = 0.0006). However, we found no significant difference between cases and controls for IgG2-specific PRP antibody, total IgG4, or total PRP antibody. The data suggest that IgG4-specific PRP antibody is elicited by invasive H. influenzae type b disease, independent of age. The IgG4 subclass thus may be a critical determinant of the immune response to invasive infection caused by H. influenzae type b, especially for young infants who generally have a weak immune response to this organism.