De Novo Persistent Post-Lung Transplantation HLA Donor-Specific Antibodies (DSA) but not Preformed DSA are Associated with Worse Survival and a Higher Risk of Developing Chronic Lung Allograft Dysfunction

Background: The introduction of highly sensitive solid-phase immunoassay technology permitted better detection and characterization of donor-specific HLA antibodies (DSA) in pre- and post-transplant period; however their impact on clinical outcome after lung transplantation (LTx) remains controversial. Patients and methods: A retrospective analysis on a cohort of 138 adult recipients who had undergone LTx at the Marseille Lung Transplant Centre (France) between 1998 and 2010 was performed. Detection at Day 0, Month 1, Month 3,Month 12 and Month 24 post- LTx of HLA antibodies (Abs) and DSA was investigated using a Luminex assay. Results: Pre-LTx DSA (n=15) were not correlated to overall survival and development of CLAD. De novo DSA were frequently detected (41% of cases), appeared earlier in the post-LTx period (80% in the first month), and were mostly directed against HLA class II antigens (78% of DSA) and against putative non classical HLA antigens such as HLA-Cw and –DQA (57% of DSA). De novo post-LTx DSA detected at M3 and/or M12 significantly affected survival (p<0.001 and p=0.03, respectively) and de novo persistent DSA from M1 to M3 (16% of cohort) were associated with CLAD (p=0.02). Cox proportional hazard regression modeling, showed a worse prognosis in recipients who have persistent de novo class II DSA (OR = 2.8, 95% CI 1.2 to 6.7, p = 0.02). Conclusion: Our results highlight that more than one-third of recipients developed de novo DSA during the first year post-LTx and that their persistence overtime seems to be associated with a worse prognosis regarding graft function and survival.