Comparison of De Novo Donor Specific and Non-Specific Antibodies on the Outcome after Heart Transplantation

Abstract

Purpose Studies have shown that donor specific antibodies (DSA) have great impact on the clinical course and overall survival of patients after heart transplantation (HTx). De-novo non-DSA (NSA) were associated with graft loss after kidney transplantation, but it remains unclear to what extent NSA play a role in rejection, graft function and overall mortality after HTx. The aim of this study was to analyze and compare the outcome of patients with DSA and NSA after HTx. Methods Surveillance endomyocardial biopsies (EMB) were taken after 1, 3, 6 months and yearly for 5 years after HTX, and cardiac allograft vasculopathy (CAV) was evaluated via coronary angiography. Serum HLA-class I and II antibodies were collected for analysis of donor specifity twice yearly. The antibody mean fluorescence intensity (MFI) cut-off values were set at >1000. Study data was collected retrospectively from internal medical records. End points of the study were death of any cause, primary graft failure (PGF), biopsy proven acute cellular rejection (BPACR) ≥2R according to ISHLT, antibody mediated rejection (AMR) and CAV. Complete data was obtained only from patients with a survival of 12 months or greater. Results 69 patients with a follow-up time of min. 18 months to max. 6 years after HTx were divided into two groups (G1: no DSA or NSA present, n=41, G2: DSA and / or NSA present, n=27). G2 was further divided into two subgroups, patients with both DSA + NSA (n=9) and only NSA(n=26) status.All-cause mortality was n=21 (30.9%), with significant difference amongst the groups (G1: n=17 (41.5%), G2: n=4(18.4%)). This trend was also seen amongst cardiovascular mortality (G1: n=7 (17.1%), G2: n=0). No statistically significant difference was seen regarding CAV (G1: n=3 (7.3%), G2: n=2 (7.4%)), BPACR (G1: n=19 (27.9%) or G2: n=9 (22%)). Surprisingly, AMR was seen in patients in G1 n=3 (4.4%), but not in G2 (n=0), however, without statistically relevant difference. Conclusion Our study shows that DSA and NSA had no negative impact on the outcome up to 6 years after HTx. This might be due to a closer monitoring of the patients after detection of DSA and NSA, and, consequently, an adequate and early adjustment of immunosuppressive therapy including specific DSA treatments to preserve graft function.