Persistence of de novo DSA is associated with chronic lung allograft dysfunction and reduced survival after lung transplantation

Background De novo donor-specific anti-HLA-antibodies (dnDSA) appear frequently after lung transplantation. The impact of dnDSA on chronic lung allograft dysfunction (CLAD) and survival is still a matter of debate. In recent studies there was a growing interest in the course over time of dnDSA after transplantation.

Patients and Methods We investigated the clinical relevance of HLA-antibodies on lung allograft outcome prospectively in 89 recipients who were transplanted between 2013 and 2015. The median follow-up time was 42 months with a minimum follow-up time of 3 years per patient.

The presence of HLA-antibodies was analyzed by Luminex Single Antigen Bead assay regular prior and after transplantation (3 weeks, 3, 6, 9 and 12 months and then every 6 months) and on demand in case of graft dysfunction.

Results After transplantation 37% of the patients (n = 33) developed dnDSA. In 12 of these patients (36%) dnDSA persisted throughout the surveillance period whereas in 20 of these patients (60%) dnDSA disappeared after a median of 139 days. In one patient transient DSA turned up again. Interestingly, 78% of dnDSA appeared within the first year after transplantation and time to first DSA appearance was shorter in patients with transient compared to patients with persistent DSA (median 42 days vs. 242 days; p = 0.076). The immunosuppressive regimen was changed more frequently from tacrolimus to cyclosporine A in patients with dnDSA (p = 0.031).

Bronchiolitis obliterans syndrome (BOS) occurred in 18% of dnDSA negative patients and in 33% of dnDSA positive patients (p = 0.142). Patients with persistent DSA developed BOS significantly more often compared to DSA negative patients (56% vs. 18%, p = 0.030). There was no statistical difference between one year and three year survival of patients with and without dnDSA (88% vs. 91% and 74% vs. 75%). Remarkably, one year and three year survival of patients with persistent DSA was only 67% and 46% respectively. The Kaplan-Meier survival analysis showed a significant reduced survival of patients with persistent DSA compared to patients with transient DSA and without DSA (log-rank p = 0.001 and p = 0.012).

Conclusion Persistence of de novo DSA after lung transplantation is an important risk factor for dismal survival and is associated with a higher incidence of CLAD after lung transplantation.