E-Poster with pre-recorded video presentation Lorne Infection and Immunity 2021

Inferior outcomes in lung transplant recipients with serum Pseudomonas aeruginosa specific cloaking antibody (#215)

Amy Pham 1 , Chandima Divithotawela 2 , Peter Bell 2 3 , Emma Ledger 1 , Maxine Tan 2 , Stephanie Yerkovich 3 , Michelle Grant 2 , Peter M Hopkins 2 3 , Timothy J Wells 1 4 , Daniel C Chambers 2 3
  1. University of Queensland Diamantina Institute, Brisbane, QLD, Australia
  2. Queensland Lung Transplant Service , The Prince Charles Hospital , Brisbane, Queensland, Australia
  3. School of Medicine , The University of Queensland, Brisbane, Queensland, Australia
  4. Australian Infectious Disease Research Centre , The University of Queensland, Brisbane, Queensland, Australia

Lung transplantation is a well-accepted treatment option for patients with end-stage lung disease, however survival is limited by the development of chronic lung allograft dysfunction (CLAD) and infection. Pseudomonas aeruginosa is a nosocomial pathogen that is particularly problematic in lung transplant recipients. Infection is difficult to eradicate once established, associated with chronic inflammation, deteriorating lung function and mortality.

A paradoxical role for antibodies in patients with chronic bacterial infections have been demonstrated. Termed cloaking antibodies (cAb), O-antigen specific IgG2 and IgA antibodies in the host have been found to block complement-mediated serum killing of the infecting bacterium, and were associated with worse disease severity. Our lab has demonstrated the clinical benefits of therapeutic plasmapheresis on three separate occasions to treat cAbs. Here, we assessed the prevalence, risk factors for, and clinical impact of cAbs in a lung transplant cohort. 123 transplant recipients with 425 archived sera were screened for cAbs against a panel of three O-antigen serotypes of P. aeruginosa commonly reported in clinical infections, and confirmed by serum bactericidal assays or dilution ELISA.

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 7.03, 95% CI 3.07 – 17.07, p < 0.001; age at transplant, OR 0.93, 95% CI 0.90 – 0.96, p < 0.001). 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 < 0.001;CMV mismatch (D+/R-), HR 5.40, 95% CI 2.36 – 12.32, p < 0.001) and all-cause mortality (cAb, HR 2.75, 95% CI 1.27 – 5.95, p = 0.010, CMV mismatch, HR 3.53, 95% CI 1.62 – 7.70, p = 0.002) in multivariable regression analyses.

These findings demonstrate that cAbs are prevalent after lung transplantation, and in part explain the known association between Pseudomonas aeruginosa colonisation and CLAD, and independently predict poor outcomes. Understanding the role of these antibodies in the pathobiology of chronic pulmonary infection and CLAD will be important in developing strategies to reduce irreversible allograft injury and improve outcomes post-transplant.