Background

The presence of antibodies to angiotensin type 1 receptor (AT 1 R) and endothelin type A receptor (ET A R) is associated with allograft rejection in kidney and heart transplantation. The aim of our study was to determine the impact of AT 1 R and ET A R antibodies on graft outcome in lung transplantation.

Methods

Pretransplant and posttransplant sera from 162 lung recipients transplanted at 3 centers between 2011 and 2013 were tested for antibodies to AT 1 R and ET A R by the enzyme-linked immunosorbent assay (ELISA) assay. Clinical parameters analyzed were: HLA antibodies at transplant, de novo donor-specific antibodies (DSA), antibody-mediated rejection (AMR), acute cellular rejection, and graft status.

Results

Late AMR (median posttransplant day 323) was diagnosed in 5 of 36 recipients with de novo DSA. Freedom from AMR significantly decreased for those recipients with strong/intermediate binding antibodies to AT 1 R (P= 0.014) and ET A R (P= 0.005). Trends for lower freedom from acute cellular rejection were observed for recipients with pretransplant antibodies to AT 1 R (P= 0.19) and ET A R (P= 0.32), but did not reach statistical significance. Lower freedom from the development of de novo DSA was observed for recipients with antibodies detected pretransplant to AT 1 R (P= 0.054), ET A R (P= 0.012), and HLA-specific antibodies (P= 0.063). When the pretransplant antibody status of HLA-specific antibody (hazard ratio [HR], 1.69) was considered together with either strong binding to AT 1 R or ET A R, an increased negative impact on the freedom from the development of de novo DSA was observed (HR, 2.26 for HLA antibodies and ET A R; HR, 2.38 for HLA antibodies and ET A R).

Conclusions

These results illustrate the increased negative impact when antibodies to both HLA and non-HLA antigens are present pretransplant.