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

Abstract

Background: Chronic Lung Allograft Dysfunction (CLAD) limits long-term survival following lung transplantation. Colonization of the allograft by Pseudomonas aeruginosa 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 P. aeruginosa lipopolysaccharide cell wall (cAbs) attenuate complement-mediated bacteriolysis in suppurative lung disease.

Methods: In this retrospective cohort analysis of 123 lung transplant recipients, we evaluated the prevalence, risk factors and clinical impact of serum cAbs following transplantation.

Results: 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, p < .001; age at transplant, OR 0.69, 95% CI 0.59-0.81, p < .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, p < .001; CMV mismatch (D+/R-), HR 5.40, 95% CI 2.36-12.32, p < .001) and all-cause mortality (cAb, HR 2.75, 95% CI 1.27-5.95, p = .010, CMV mismatch, HR 3.53, 95% CI 1.62-7.70, p = .002) in multivariable regression analyses.

Conclusions: Taken together, these findings suggest a potential role for 'cloaking' antibodies targeting P. aeruginosa LPS O-antigen in the immunopathogenesis of CLAD.

Keywords: Pseudomonas aeruginosa; chronic lung allograft dysfunction; cloaking antibodies; cytomegalovirus; lung transplantation.