Natural immunity against Haemophilus influenzae type a and B-cell subpopulations in adult patients with severe chronic kidney disease

Abstract

Individuals suffering from severe chronic kidney disease (CKD) are immunocompromised and therefore highly susceptible to various infections including Haemophilus influenzae type a (Hia), an emerging pathogen in North American Indigenous populations. Immunocompromised Indigenous adults are considered a target for a new Hia vaccine under development. In an attempt to foresee their response to Hia immunization, we studied natural immunity against Hia and B-cell subpopulations in sixty patients with CKD residing in a geographic region with noticeable presence of Hia invasive disease. Serum bactericidal activity (SBA) against Hia, concentrations of IgG and IgM antibodies specific to Hia capsular polysaccharide, and B-cell subpopulations were studied in patients with CKD and 35 healthy controls of the same age. Of the patients with CKD, proportions and absolute numbers of B-cell subpopulations were determined for 28 patients. The patients had lower SBA titres compared to controls. Although no significant differences in anti-Hia IgG or IgM antibody concentrations between control and CKD groups were found, IgM antibody concentrations were higher in Indigenous than non-Indigenous patients. Patients with CKD had a higher proportion of B cells (CD19+), class switched memory B cells (CD19+CD27+IgM-) and a lower proportion of CD19+CD27-IgM- B cells compared to healthy controls. Non-Indigenous patients with CKD had significantly higher proportions of IgM memory B cells and CD19+CD27-IgM- B cells compared to Indigenous patients with no significant difference in absolute numbers. Because 72% of CKD patients had detectable SBA titres and 100% had detectable IgG and IgM antibodies it is possible that a portion of IgM memory B cells and class switched memory B cells are specific for Hia resulting from a natural exposure to the pathogen. The data suggest that a Hia-conjugate vaccine may be immunogenic in adult patients with CKD as it will potentially induce re-activation of immunological memory against Hia.

Keywords: B cells; ELISA; Flow cytometry analysis; Haemophilus influenzae type a; Serum bactericidal assay; Severe chronic kidney disease.