Treatment of Pseudomonas by Removal of Cloaking Antibodies: Is Common Polysaccharide Antigen a Factor?

backgroundPeople with cystic fibrosis (pwCF) are susceptible to chronic lung infections, particularly with Pseudomonas aeruginosa. During infection, a subset of patients develops cloaking antibodies specific to O-antigen lipopolysaccharide that impair complement-mediated bactericidal killing. These antibodies associate with worse disease, and their removal via plasmapheresis has been used as a successful treatment for multidrug-resistant P aeruginosa. Whether a similar mechanism of antibody-mediated serum resistance exists toward common polysaccharide antigen (CPA) lipopolysaccharide is unknown.

methodsForty-two serum samples and 63 matched P aeruginosa isolates were collected from pwCF. The titers of antibodies specific to CPA in patient sera were determined, and the ability of these antibodies to inhibit serum-mediated killing of P aeruginosa was assessed.

resultsDespite widespread anti-CPA antibodies, only 1 serum-strain pair showed evidence of complement inhibition. Patient serum IgG and IgA responses to CPA were elevated in 86% and 69% of sera, respectively. Furthermore, 69% of pwCF were colonized with CPA-expressing isolates. Despite the high prevalence of elevated anti-CPA antibodies, only 1 patient had antibodies capable of inhibiting complement killing of the cognate P aeruginosa. This isolate, CFP3A, had significantly higher expression of CPA than all other strains. Complement-mediated killing toward it was inhibited by anti-CPA antibodies in a titer-dependent manner.

conclusionsThis investigation reveals that although antibody specific for CPA is prevalent in pwCF, it cannot inhibit complement killing of the majority of CPA-expressing strains. Thus, when Pseudomonas is treated by removal of cloaking antibodies, it is unlikely that CPA-specific antibodies will also need to be eliminated.