P074 Donor specific anti-HLA antibodies are associated with subclinical allograft injury in heart transplant recipients

Abstract

Aim Anti-HLA antibodies detected after heart transplantation have been associated with graft rejection and worse survival. However, the presence of donor specific antibodies (DSA) alone is not diagnostic of antibody mediated rejection (AMR). To better define the significance of circulating DSA, we investigated the relationship between DSA and relevant histo- and immunopathologic features of endomyocardial biopsies. Methods Sixty-three patients received heart transplantation between Jan 1st 2011 and Dec 31st 2013 and were followed at our center. Serum anti-HLA antibodies were monitored using the Single Antigen Bead assay (One Lambda, Canoga Park, CA). Endomyocardial biopsies were performed serially during the first year post-transplant and yearly thereafter, according to the existing clinical protocol. Results At a median followup time of 33 months, graft/patient survival was 98%. Sixteen (25%) out of 63 patients had at least 2 DSA positive tests after transplantation. DSA were predominantly directed to HLA class II antigens, with 13 out of 16 patients displaying anti-HLA-DQ DSA. A total of 906 endomyocardial biopsies were performed after transplantation. Out of 906, 305 biopsies had concomitant DSA results and were included in the analysis. Fifty-seven (19%) biopsies had positive DSA associated results. ACR was diagnosed in 60 (20%) out of 305 biopsies. There was no significant correlation between ACR and serum DSA. AMR was diagnosed in one (0.3%) biopsy, which had a concomitant positive DSA. The following histo- and immunopathologic parameters were analyzed in relation to DSA: perivascular inflammation, interstitial inflammation, myocyte injury, lymphocytic infiltration, interstitial edema, interstitial hemorrhage, fibrosis, microvascular changes and C4d staining. Microvascular changes included prominent endothelial cells and intravascular mononuclear cells and/or neutrophils. DSA were associated with microvascular changes (N = 9; p Conclusion Our results provide evidence that circulating DSA are associated with subclinical graft injury. Post-transplant DSA monitoring may serve as a useful, non-invasive tool to identify patients at risk for early graft loss.