Cystic fibrosis (CF) is among the most prevalent autosomal recessive disease in Australia affecting 1 in 2500 infants. It is a multi-system disease, yet the most serious complications manifests in the airways due to chronic pulmonary infection. Infection by P. aeruginosa, and members of the Burkholderia cepacia complex (BCC) is associated with chronic inflammation, increased mortality, and impaired health related quality of life. The BCC is particularly contradictory as it precludes patients from lung transplantation due to the significant post-operative mortality associated with the bacterium.
Antibodies usually aid to protect against infection, however paradoxical roles of antibodies in patients with chronic bacterial infections have been described. Termed cloaking antibodies (cAb), O-antigen specific antibodies in the host has been shown to block complement-mediated serum killing of the infecting bacterium. High titres of cAbs inhibit serum mediated killing by binding to the O-antigen and creating a physical barrier that prevents the access of complement proteins from the bacterial membrane. The presence of cAbs has been reported in several P. aeruginosa-mediated disease settings, including non-CF bronchiectasis (20%), CF (32%) and lung transplant recipients (40%), and more importantly associated with increased severity of disease. The clinical benefits of therapeutic plasmapheresis and IVIG treatment have been demonstrated on three separate occasions to treat cAbs and ameliorate infection.
As the O-antigen is the key inhibitory determinant that mediates the inhibition of complement mediated killing in serum, cAbs could exist against any Gram-negative infection. Here, we investigated the presence of cAbs in a cohort of patients with cystic fibrosis (n = 9) with Burkholderia spp. (B. cenocepacia, B. multivorans, B. anthina, B. gladioli) lung infection. Patient sera was screened for the presence of cAbs against the LPS of their cognate isolates via an ELISA, and inhibition phenotype confirmed via a serum bactericidal assay. cAbs were detected in the sera of 4/9 patients, with anti-LPS IgA and IgG found to inhibit serum killing of Burkholderia spp.