Treatment of Pseudomonas by removal of cloaking antibodies; is common polysaccharide antigen a factor?

Abstract

People with cystic fibrosis (pwCF) are susceptible to chronic lung infections, particularly with Pseudomonas aeruginosa. During infection, a subset of patients develop cloaking antibodies (cAb) specific to O-antigen lipopolysaccharide (LPS) 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 multi-drug-resistant P. aeruginosa. Whether a similar mechanism of antibody-mediated serum resistance exists towards common polysaccharide antigen (CPA) LPS is unknown. Forty-two serum samples and 63 matched P. aeruginosa isolates were collected from pwCF. The titres 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. Despite widespread anti-CPA antibodies, only one 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. Further, 69% of pwCF were colonised with CPA-expressing isolates. Despite high prevalence of elevated anti-CPA antibodies, only one patient had antibodies capable of inhibiting complement killing of their cognate P. aeruginosa. This isolate, CFP3A, had significantly higher expression of CPA than all other strains. Complement-mediated killing towards it was inhibited by anti-CPA antibodies in a titre dependent manner. This 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 treating Pseudomonas by removing cloaking antibodies, it is unlikely that CPA-specific antibodies will also need to be eliminated.