Non-HLA autoantibodies supplement donor specific antibodies in predicting graft survival after heart transplantation

Abstract

Abstract Background Presence of antibodies to donor-specific human leukocyte antigens (HLA) is a well-known risk factor associated with outcome in heart transplantation (HTx). However, non-HLA have also been associated with graft outcomes in HTx. Purpose We sought to assess the effect of non-HLA antibodies on graft outcome in Korean HTx patients. Methods Pre-transplant serum from patients undergoing HTx from January 2014 to December 2016 in four large transplant centers in Korea were analyzed. Presence of increased non-HLA antibodies, and their association with early (≤ 1-year) and long-term graft failure were assessed. Results Non-HLA antibodies were assessed in 192 patients. Antibodies to vimentin (AVA+) and type II collagen (ACA+) were associated with a lower rate of 1-year graft survival (78.6% vs. 92.6%-, log-rank p=0.006 for AVA+; 72.2% vs. 91.1%, log-rank p=0.015 for ACA+). Additionally, AVA+ stratified 1-year graft survival in patients with donor specific antibodies (DSA+) (45.5% vs. 94.1%, log-rank p=0.002). AVA+ also improved the prediction model for 1-year graft survival when added to known risk factors (IDI=11%, p=0.002; NRI=23%, p=0.047). ACA+ was also associated with lower rates in late graft survival (66.3% vs. 88.6%, log-rank p<0.001). Compared to AVA-/ACA- patients, AVA+/ACA+ patients had significantly poor graft survival both in the early and late periods (all log-rank p<0.001). Conclusion In our analysis of patients undergoing HTx, presence of non-HLA antibodies to vimentin and type II collagen were associated with poor graft outcomes. Pre-transplant assessment of non-HLA antibodies could help predict outcomes and tailor graft allocation and post-HTx immunotherapy in specific patients.Kaplan-Meier curves for graft survival