Introduction: Chronic leg wounds are a major burden of disease. Recent work showed that ‘cloaking antibodies’ made up of IgG2 or IgA specific for lipopolysaccharide paradoxically protect P. aeruginosa by interrupting the complement pathway. Cloaking antibodies (cAbs) have been associated with worse clinical outcomes for patients with P. aeruginosa lung infections, where clearance of cAbs using plasmapheresis led to eradication of multi-drug resistant infection. The prevalence of cAbs in leg ulcers has not been determined.
Methods: In this prospective cohort study, patient clinical data along with wound swabs and blood were collected at baseline. Bacterial species identification was done via MALDI-TOF. Sera was tested for cAbs targeting P. aeruginosa via ELISA. Inhibition of serum killing was verified by serum bactericidal assays (SBA). Clinical data was collected at 12, 24 and 48 week timepoints.
Findings: Forty-seven patients were recruited. Eleven patients (26.8%) were culture positive for P. aeruginosa. None of these P. aeruginosa positive wounds healed, whilst those not colonised had higher rates of healing (41%, p=0.018). Antibody analysis of 45 sera showed 26 (57.7%) of these had high titres of IgG cAbs. In 43 patients seen at follow-up, the presence of cAb did not impact healing: among those with presence of cAb, 34.6% (9/26) healed compared to 23.5% (4/17) of healed wounds with no cAb. Patients with current or previous P. aeruginosa colonisation were more likely to carry cAb (IgG), compared to patients with no known colonisation (12/19 (63%) vs 14/26 (53.8%), p=0.55). SBAs confirmed that cAbs protected P. aeruginosa in 56% of cases tested, allowing it to survive in complement rich environments like blood or wound fluid.
Conclusion: cAbs are prevalent in chronic wound patients. Whilst they might not influence healing, they potentially make eradication of P. aeruginosa more difficult, predisposing patients to more severe episodes of infection.