Inferior outcomes in lung transplant recipients with serum Pseudomonas aeruginosa specific cloaking antibodies

Abstract

<h3>Background</h3> Chronic Lung Allograft Dysfunction (CLAD) limits long-term survival following lung transplantation. Colonization of the allograft by <i>Pseudomonas aeruginosa</i> is associated with an increased risk of CLAD and inferior overall survival. Recent experimental data suggests that ‘cloaking' antibodies targeting the O-antigen of the <i>P. aeruginosa</i> lipopolysaccharide cell wall (cAbs) attenuate complement-mediated bacteriolysis in suppurative lung disease. <h3>Methods</h3> In this retrospective cohort analysis of 123 lung transplant recipients, we evaluated the prevalence, risk factors and clinical impact of serum cAbs following transplantation. <h3>Results</h3> cAbs were detected in the sera of 40.7% of lung transplant recipients. Cystic fibrosis and younger age were associated with increased risk of serum cAbs (CF diagnosis, OR 6.62, 95% CI 2.83-15.46, <i>p</i> < .001; age at transplant, OR 0.69, 95% CI 0.59-0.81, <i>p</i> < .001). Serum cAbs and CMV mismatch were both independently associated with increased risk of CLAD (cAb, HR 4.34, 95% CI 1.91-9.83, <i>p</i> < .001; CMV mismatch (D+/R-), HR 5.40, 95% CI 2.36-12.32, <i>p</i> < .001) and all-cause mortality (cAb, HR 2.75, 95% CI 1.27-5.95, <i>p</i> = .010, CMV mismatch, HR 3.53, 95% CI 1.62-7.70, <i>p</i> = .002) in multivariable regression analyses. <h3>Conclusions</h3> Taken together, these findings suggest a potential role for ‘cloaking' antibodies targeting <i>P. aeruginosa</i> LPS O-antigen in the immunopathogenesis of CLAD.