(470) The role of cloaking antibodies in Burkholderia cepacia complex lung infections

Background: Infection by the Burkholderia cepacia complex (BCC) in patients with CF results in a highly variable and unpredictable course of clinical infection, with a subset developing “cepacia syndrome”, a necrotising pneumonia. Infection by BCC is particularly contradictory as it can preclude patients from lung transplantation, an invaluable treatment option for end stage lung disease. Antibodies usually aid to protect against infection, however paradoxical roles of antibodies in patients with Gram-negative infections have been reported, including several cases in patients with CF and Pseudomonas aeruginosa infection. Characterised as ‘cloaking antibodies’ (cAb), these O-antigen specific antibodies actually protect Pseudomonas aeruginosa by inhibiting complement-mediated serum killing, and more importantly have been associated with worse disease severity. The clinical benefits of therapeutic plasmapheresis and IVIG treatment have been demonstrated on three separate occasions to treat cAbs and ameliorate infection. The prevalence of cAbs in BCC infection has not yet been determined.

Methods: Here, we investigated the presence of cAbs in a prospective cohort of patients (n = 12) with BCC lung infection. Patient sera was screened for the presence of antibodies specific for the O-antigen of their cognate isolates via ELISA. The ability for this antibody to inhibit healthy control serum killing of the patient’s isolate was determined via serum bactericidal assay.

Results: Cloaking antibodies were detected in the sera of 5/12 patients (41.6%). These anti-O-antigen IgA and IgG were found to inhibit serum killing of the patients BCC isolate.

Conclusions: Cloaking antibodies are prevalent in this cohort of patients with BCC infections. Treatment with plasmapheresis and IVIG to remove these antibodies may be useful to ameliorate infection.

Acknowledgements: This work was supported by the Cystic Fibrosis Foundation (US) Pilot and Feasibility Award Fall 2020

References: