Occurrence of HLA- and Non-HLA Antibodies after Heart Transplantation are Associated with Cardiac Allograft Vasculopathy

Abstract

Aims Cardiac allograft vasculopathy (CAV) accounts for major morbidity and mortality late in the heart transplant (HTx) history. The role of antibodies (Abs) directed against human leukocyte antigens (HLA) and non-HLA antigens in the pathogenesis of CAV are still under investigation. Material and methods Sera of 116 long-term HTx recipients with CAV (n=46) and without CAV (n=70) were analysed by (1) Luminex for Abs against both HLA classes and major histocompatibility complex class I-related chain A (MICA), and by (2) ELISA for Abs against angiotensin-type-1-receptor (AT1R) or endothelin-receptor-A (ETAR). Cellular rejection by endomyocardial biopsies and immunosuppressive drug therapy were analysed, too. Results HTx recipients developed higher levels of non-HLA-Abs than of Abs against HLA. CAV appeared more frequently in recipients with non-HLA-Abs (38.3% AT1R; 44.1% ETAR; 13.0% MICA) than in recipients with HLA-Abs (8.7% HLA class I; 8.7% HLA class II). Recipients with non-HLA-Abs developed CAV earlier (73.7+/-47.4months) than recipients without Abs (85.5+/-50.6months). Conclusion Occurrence of HLA-Abs and non-HLA-Abs contribute to CAV after HTx. Non-HLA-Abs were connected to an earlier and higher incidence of CAV. Recipients with subclinical cellular rejections and AT1R-Abs and ETAR-Abs as well as recipients with certain donor specific-Abs again HLA and MICA specifities are at risk to develop CAV.