A Novel Pseudomonas aeruginosa Virulence Factor Predicts CLAD and Death after Lung Transplantation

Purpose Gram -ve bacteria have recently been found to induce O-antigen-specific IgG2 and IgA ‘inhibitory’ antibodies (iAb) in the host which are not only impotent but block complement-mediated killing. Our group has demonstrated the clinical benefit of plasmapheresis in patients infected with Pseudomonas aeruginosa (Psa) strains which have deployed this virulence factor. Here we assessed the prevalence and clinical impact of iAb in a large lung transplant cohort. Methods Our centre maintains a biobank of sera from the majority of recipients. Recipients with at least one archival serum sample from the first post-transplant year were included. Presence of iAb in sera was determined by measuring titre of IgG2 and IgA against the three most prevalent (∼80% coverage) local Psa serotypes. Presence of iAb was confirmed by serum-bactericidal assays against serotype matched Psa. Results 123 recipients (54(44%) female; aged 54yrs (range 19-70); 38(31%) cystic fibrosis (CF), 89(72%) Psa colonised; median follow-up 33 (19.3-70.6) months) with 425 archived sera were studied. 25% of the whole cohort and 47% of CF subjects had iAb. iAb were persistent in subjects with multiple sera. The demographic factors independently associated with iAb were CF (OR 4.52, 95% CI 1.83-11.23, p 0.001) and younger age (OR 0.95, 95% CI 0.92-0.98, p 0.002); however, Psa-colonisation, gender, transplant type, CMV status, induction agent use and follow-up time were unassociated. In those with iAb, CLAD-free and overall survival was inferior in all (overall, CF, Psa-colonised) cohorts (Figure 1). iAb and CMV mismatch status but not Psa-colonisation status, were independently associated with inferior CLAD free survival and overall survival. Conclusion iAb are prevalent after lung transplantation, in part explain the known association between Psa-colonisation and CLAD, and independently predict poor outcomes. Development of strategies to counter iAb could significantly improve outcomes in patients with Gram -ve infection.