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.
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