High prevalence of subclass-specific binding and neutralizing antibodies against toxins in adult cystic fibrosis sera: possible mode of immunoprotection against symptomatic infection.

OBJECTIVES

Despite multiple risk factors and a high rate of colonization for , the occurrence of infection in patients with cystic fibrosis is rare. The aim of this study was to compare the prevalence of binding toxin-specific immunoglobulin (Ig)A, IgG and anti-toxin neutralizing antibodies in the sera of adults with cystic fibrosis, symptomatic infection (without cystic fibrosis) and healthy controls.

METHODS

Subclass-specific IgA and IgG responses to highly purified whole toxins A and B (toxinotype 0, strain VPI 10463, ribotype 087), toxin B from a toxin-B-only expressing strain (CCUG 20309) and precursor form of B fragment of binary toxin, pCDTb, were determined by protein microarray. Neutralizing antibodies to toxins A and B were evaluated using a Caco-2 cell-based neutralization assay.

RESULTS

Serum IgA anti-toxin A and B levels and neutralizing antibodies against toxin A were significantly higher in adult cystic fibrosis patients (n=16) compared with healthy controls (n=17) and patients with symptomatic infection (n=16); ≤0.05. The same pattern of response prevailed for IgG, except that there was no difference in anti-toxin A IgG levels between the groups. Compared with healthy controls (toxins A and B) and patients with infection (toxin A), sera from cystic fibrosis patients exhibited significantly stronger protective anti-toxin neutralizing antibody responses.

CONCLUSION

A superior ability to generate robust humoral immunity to toxins in the cystic fibrosis population is likely to confer protection against symptomatic infection. This protection may be lost in the post-transplantation setting, where sera monitoring of anti- toxin antibody titers may be of clinical value.